ANTIDEPRESSANTS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
ii
ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Antidepressants: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83735-X 1. Antidepressants-Popular works. I. Title.
iii
Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
[email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.
iv
Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on antidepressants. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
v
About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
vi
About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
vii
Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ANTIDEPRESSANTS ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Antidepressants ............................................................................ 6 E-Journals: PubMed Central ....................................................................................................... 62 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND ANTIDEPRESSANTS ......................................................................... 81 Overview...................................................................................................................................... 81 Finding Nutrition Studies on Antidepressants ........................................................................... 81 Federal Resources on Nutrition ................................................................................................... 94 Additional Web Resources ........................................................................................................... 95 CHAPTER 3. ALTERNATIVE MEDICINE AND ANTIDEPRESSANTS ................................................... 97 Overview...................................................................................................................................... 97 The Combined Health Information Database............................................................................... 97 National Center for Complementary and Alternative Medicine.................................................. 98 Additional Web Resources ......................................................................................................... 104 General References ..................................................................................................................... 113 CHAPTER 4. DISSERTATIONS ON ANTIDEPRESSANTS ................................................................... 115 Overview.................................................................................................................................... 115 Dissertations on Antidepressants .............................................................................................. 115 Keeping Current ........................................................................................................................ 116 CHAPTER 5. CLINICAL TRIALS AND ANTIDEPRESSANTS .............................................................. 117 Overview.................................................................................................................................... 117 Recent Trials on Antidepressants .............................................................................................. 117 Keeping Current on Clinical Trials ........................................................................................... 122 CHAPTER 6. PATENTS ON ANTIDEPRESSANTS .............................................................................. 125 Overview.................................................................................................................................... 125 Patents on Antidepressants ....................................................................................................... 125 Patent Applications on Antidepressants.................................................................................... 136 Keeping Current ........................................................................................................................ 153 CHAPTER 7. BOOKS ON ANTIDEPRESSANTS.................................................................................. 155 Overview.................................................................................................................................... 155 Book Summaries: Federal Agencies............................................................................................ 155 Book Summaries: Online Booksellers......................................................................................... 159 The National Library of Medicine Book Index ........................................................................... 163 Chapters on Antidepressants ..................................................................................................... 164 CHAPTER 8. MULTIMEDIA ON ANTIDEPRESSANTS ....................................................................... 179 Overview.................................................................................................................................... 179 Video Recordings ....................................................................................................................... 179 Audio Recordings....................................................................................................................... 180 Bibliography: Multimedia on Antidepressants .......................................................................... 180 CHAPTER 9. PERIODICALS AND NEWS ON ANTIDEPRESSANTS .................................................... 183 Overview.................................................................................................................................... 183 News Services and Press Releases.............................................................................................. 183 Newsletter Articles .................................................................................................................... 187 Academic Periodicals covering Antidepressants........................................................................ 188 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 189 Overview.................................................................................................................................... 189 U.S. Pharmacopeia..................................................................................................................... 189 Commercial Databases ............................................................................................................... 191
viii Contents
APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 195 Overview.................................................................................................................................... 195 NIH Guidelines.......................................................................................................................... 195 NIH Databases........................................................................................................................... 197 Other Commercial Databases..................................................................................................... 201 APPENDIX B. PATIENT RESOURCES ............................................................................................... 203 Overview.................................................................................................................................... 203 Patient Guideline Sources.......................................................................................................... 203 Finding Associations.................................................................................................................. 206 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 209 Overview.................................................................................................................................... 209 Preparation................................................................................................................................. 209 Finding a Local Medical Library................................................................................................ 209 Medical Libraries in the U.S. and Canada ................................................................................. 209 ONLINE GLOSSARIES................................................................................................................ 215 Online Dictionary Directories ................................................................................................... 217 ANTIDEPRESSANTS DICTIONARY ....................................................................................... 219 INDEX .............................................................................................................................................. 311
1
FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with antidepressants is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about antidepressants, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to antidepressants, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on antidepressants. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to antidepressants, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on antidepressants. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
3
CHAPTER 1. STUDIES ON ANTIDEPRESSANTS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on antidepressants.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and antidepressants, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “antidepressants” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Antidepressants for Functional Gastrointestinal Syndromes Source: Digestive Diseases and Sciences. 39(11): 2352-2363. November 1994. Summary: Antidepressant agents have been suggested as treatments for functional gastrointestinal syndromes since the early 1960s. Their efficacy has been demonstrated through anecdotal reports and a small number of controlled studies, but the best candidates for treatment remain unknown. In this article, the author describes the rationale for trying antidepressants for the functional disorders, the outcome of reported studies in several of the syndromes, and a discussion of potential modes of action in these illnesses. A final section summarizes the author's personal experience using these agents in clinical practice. 5 figures. 5 tables. 82 references. (AA).
4
Antidepressants
•
Antidepressants and Functional Gastrointestinal Disorders (editorial) Source: Practical Gastroenterology. 25(4): 16, 19-20, 23. April 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Antidepressants are commonly prescribed for the treatment of functional gastrointestinal disorders. This article describes the three unique properties of these drugs that make them useful for these disorders. The first is the mechanism of action of antidepressants, i.e., how they exert their effect. The second is the relationship between the brain and the gut, the so-called 'brain gut axis.' Finally is the role of antidepressants in treating the various symptoms of functional gastrointestinal disorders. The author reviews these properties in order to help physicians determine whether these drugs are appropriate for their patients with gastrointestinal disorders. Drugs discussed include monoamine oxidase (MAO) inhibitors, tricyclic antidepressants, and selective serotonin reuptake inhibitors (SSRIs). The major antidepressant effect of these drugs comes from their ability to block the reuptake of either norepinephrine (NE) or serotonin, which is also known by its chemical name, 5 hydroxytriptamine (5HT); the SSRIs do not affect the uptake of norepinephrine. It has been recognized for some time that the enteric nervous system of the gut, beginning in the esophagus and extending all the way into the anorectal area, is richly innervated with nerves that contain large amounts of NE and 5HT. The author summarizes studies done on the usefulness of these drugs in functional gastrointestinal disorders. The author concludes that these drugs play a role in the biopsychosocial model of treatment, where multiple dimensions of the patient's life, including gut function, overall well being, as well as overall quality of life and emotional status seems reasonable. The use of diet therapy, antispasmodics, antidiarrheals, antidepressants, and behavioral interventions such as biofeedback, psychotherapy, and relaxation therapy all play an important role in improving outcomes in functional gastrointestinal disorders.
•
Use of Antidepressants in Irritable Bowel Syndrome Source: Practical Gastroenterology. 26(3): 13-14, 19-20, 22-23, 27. March 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Irritable bowel syndrome (IBS) is the most common bowel disorder seen in gastroenterology practice. IBS is characterized by a pattern of waxing and waning abdominal pain, bloating, and disturbance of bowel habits. This article describes the rationale for the use of antidepressants in IBS, the results of clinical trials, suggested treatment plan, and directions for future research. The authors note that IBS is a complex biopsychosocial disorder whose precise pathophysiology is unknown, although it is generally accepted that abnormal brain-gut interactions play a major role. At the time of clinical presentation, about 50 percent of IBS patients have a definable psychiatric disorder. Psychosocial stressors have been demonstrated to have an important modulatory role in IBS, affecting not only the illness experience but also health care seeking behavior and the clinical outcome. Antidepressants represent an attractive therapeutic approach for the treatment of IBS, not only for their psychotropic effects, but also for their neuromodulatory and analgesic properties. However, there is still a lack of well-designed, appropriately powered, randomized clinical trials examining the use of antidepressants in IBS. 1 figure. 4 tables. 51 references.
Studies
•
5
Antidepressant Use in Psychiatry and Medicine: Importance for Dental Practice Source: JADA. Journal of the American Dental Association. 134(1): 71-79. January 2003. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Many dental patients receive antidepressant therapy. However, antidepressants taken with other drugs may increase the risk of complications that require special dental precautions and care. This article reports on a retrospective study of 1,800 randomly selected patient records and evaluated the prevalence of using antidepressants and other medications concurrently. The authors analyzed antidepressant intake relative to drug classification and mechanism of action, age, sex, and associated potential for clinical complications such as xerostomia, orthostatic hypotension, and interaction with vasoconstrictors. Of the 1,800 patients, 381 (21 percent) were being treated with 412 antidepressants. Female subjects outnumbered male subjects by a 2.3 to 1 ratio. Selective serotonin reuptake inhibitors were most commonly prescribed, followed by tricyclic antidepressants, atypical and thirdgeneration antidepressants, and monoamine oxidase inhibitors. Based on reported medication intake, almost 58 percent of subjects in the antidepressant group were receiving treatment with two or more medications that had the potential for producing xerostomia (dry mouth). Two hundred fifty-seven (67 percent) of the 381 records documented intake of an antidepressant or other medication with orthostatic hypotension (low blood pressure upon assuming a standing position). 3 figures. 3 tables. 89 references.
•
Risks for Oral Health with the Use of Antidepressants Source: General Hospital Psychiatry. 20(3): 150-154. May 1998. Contact: Available from Elsevier Science. P.O. Box 945, New York, NY 10010. (800) 4374636 or (212) 633-3730. Fax (212) 633-3680. E-mail:
[email protected]. Summary: This article explores the risks for oral health with the use of antidepressants. The authors focus their attention on oral pathology, particularly dental caries, caused by hyposalivation (low salivation) as a consequence of long term use of antidepressants. Changes in clinical psychiatric practice and increasing numbers of prescriptions of antidepressants in primary care and specialty care settings have made awareness of this risk even more relevant than in the past. The authors describe the normal physiology of salivary glands and changes in the secretion of saliva during use of antidepressants. The consequences of drug-induced hyposalivation include dryness of the mouth (xerostomia), thirst, nocturnal oral discomfort, burning sensation, periodontal disease, progressive dental caries, oral functioning difficulties, and denture discomfort. The article includes a case report of a 51 year old male patient being treated with clomipramine 300 mg daily for severe recurrent major depression. The authors encourage monitoring, prevention, and treatment of hyposalivation induced by antidepressants, as an adjunct in the clinical management of depression. 2 tables. 29 references.
•
Antidepressant Medications: Do They Have a Role in Treating Irritable Bowel? Source: Intestinal Fortitude. 5(2): 1-2. Fall 1994. Contact: Available from Intestinal Disease Foundation. 1323 Forbes Avenue, Suite 200, Pittsburgh, PA 15219. (412) 261-5888.
6
Antidepressants
Summary: This article explores the role of antidepressant medications in the treatment of irritable bowel syndrome (IBS). The author stresses that most patients may need to allow a significant amount of trial and error in order to find the most helpful medications. Topics covered include the types of medications that are commonly prescribed for IBS; the use of tricyclic antidepressants; antispasmodic effect; analgesic effects; relief of depression; and side effects of medications, including constipation, dry mouth, sluggish urination, and over-sedation in the daytime.
Federally Funded Research on Antidepressants The U.S. Government supports a variety of research studies relating to antidepressants. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to antidepressants. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore antidepressants. The following is typical of the type of information found when searching the CRISP database for antidepressants: •
Project Title: 5-HT2C-RECEPTOR EXPRESSION AND FUNCTION IN DEPRESSION Principal Investigator & Institution: Schmauss, Claudia; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Applicant's abstract) The expression and function of one subtype of serotonin (5-HT) receptors, the 5-HT2C receptor, is regulated by RNA editing and alternative splicing of its encoded pre-mRNA. In postmortem prefrontal cortical tissue from depressed suicide victims, the editing pattern of 5-HT2C pre-mRNA differs significantly from the editing pattern of control brains that could potentially result in a decreased efficiency of 5-HT2C receptor-G protein interactions. The overall objectives of the proposed research plan are to varify further a possible relationship between depression and an altered editing pattern of prefrontal cortical 5-HT2C pre-mRNA, and to define the possible functional consequences of this altered editing pattern and to test possible underlying mechanisms. Three specific aims are proposed to attain these objectives. In specific aim 1, the investigator proposes an extended replication of the differential 5-HT2C editing finding piloting this work. The 5-HT2C receptor editing pattern would be compared in brains of groups of male depressed suicide victims and depressed non-suicide subjects to assess the relative contribution of depression versus suicide. Editing patterns of 5-HT2C receptor mRNAs would be identified by nucleotide sequencing of cDNAs generated by RT-PCR. Proposed specific aim 2 would assess the
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
7
functional significance of altered 5 HT2C receptor mRNA editing using stably transfected lines of NIH3T3 cells that express the three major altered 5-HT2C receptor isoforms associated with depression, as well as the more rare nonedited and fully edited isoforms. Functional assays would determine the comparative ability of the edited and nonedited isoforms to couple to G protein and activate the phospholipase C second messenger system. The effects of RNA editing on the guanyl nucleotide sensitivity of 5HT2C receptor-G protein interactions, and the interaction of different receptor isoforms would also be preliminarily assessed. Related functional experiments would compare GTP(S binding to membranes of prefrontal cortical tissues of depressed suicide victims and depressed non-suicide subjects to determine the effect of 5-HT2C editing alterations associated with depression on basal and agonist-promoted activation of G proteins by 5HT2C receptors. Specific aim 3 would compare the effects of mechanistically distinct antidepressants, and the 5-HT2A/2C receptor antagonist ketanserin, on the neocortical 5-HT2C receptor RNA editing pattern, in wild-type mice. These studies would attempt to assess whether the observed alteration of 5-HT2C RNA editing in depression reflects medication effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACUTE REGULATION OF NOREPINEPHRINE TRANSPORTERS Principal Investigator & Institution: Blakely, Randy D.; Associate Professor; Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 31-JUL-2003 Summary: The magnitude and duration of chemical neurotransmission is determined by reciprocal presynaptic activities of neurotransmitter release and reuptake. At sympathetic synapses of the vertebrate autonomic system, the catecholamine neurotransmitters norepinephrine (NE) and epinephrine (Epi) are rapidly cleared by transporter proteins thought to be enriched in presynaptic terminals and varicosities. The efficient recovery of NE and Epi permits repetitive sympathetic signaling without synaptic receptor desensitization, spatially limits the response to neurotransmitter, and helps maintain presynaptic catecholamine stores necessary for sustained signaling. Alterations in NE transport, as occurs with pharmacologic blockade by cocaine or tricyclic antidepressants, leads to a an augmentation of synaptic responses, a spillover of NE out of the synapse, the triggering of extrasynaptic receptors, and subsequent receptor desensitization. Whereas the kinetic behavior and drug sensitivities of catecholamine transporters are well described, molecular details of transporter structure, localization, and regulation have been unavaIlable. Recently, we have cloned the first cDNAs encoding cocaine and antidepressant-sensitive NE transporters (NETs) from the human medulloblastoma SK-N-SH, characterized the functional properties of expressed carriers in transfected cells, and developed NET specific antibodies for biochemical and immunocytochemical studies. We now propose to 1) identify and dissect homologous NETs and Epi transporters (ETs) expressed in the vertebrate heart, 2) elucidate molecular mechanisms for acute NET regulation using radiotracer flux and ligand binding, single cell electrophysiological techniques, and biochemical analysis of modified NET protein and 3) determine where and how transporters are spatially localized to presynaptic terminals using autoradiography and immunocytochemistry. To accomplish these objectives, we will perform experiments on individual gene products in reconstituted systems as well as primary tissues expressing NETs. Data from these studies should substantially augment our understanding of presynaptic control mechanisms involved in sympathetic neurotransmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
8
Antidepressants
•
Project Title: ANIMAL DEPRESSION
MODELS OF CHILDHOOD AND ADOLESCENT
Principal Investigator & Institution: Bylund, David B.; Professor and Chair; Pharmacology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2003; Project Start 14-AUG-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Major Depressive Disorder (clinical depression) is a severe and potentially incapacitating mental illness that is common in children and adolescents, with an estimated lifetime prevalence of 15 -20 % in this population. An important difference between clinical depression in children and adolescents, as compared to adults, is its response to antidepressant drugs. Tricyclic antidepressants have not been shown to be effective in treatment of child and adolescent clinical depression. Although antidepressant drugs have numerous neurochemical actions, the therapeutic mechanisms of action of antidepressant drugs in relieving depression remain unknown. In non-depressed persons antidepressant drugs are not euphoriant or stimulant. Therefore, investigations related to which of the many neurochemical effects of antidepressant drugs are functionally related to their therapeutic efficacy in relieving depression requires research using a behavioral animal model of clinical depression. To better understand the neurobiology underlying the differences between children and adolescents, and adults in the response to pharmacological treatment of clinical depression, animal models of childhood and adolescent depression are needed. Currently, there are no established juvenile animal models of clinical depression. Although the models developed in adult animals can serve as a starting point, they must be adapted and validated in juvenile animals due the many differences between juvenile and adult animals. The overall goal of this proposal is to assess the validity and usefulness of two well-established rat animal models of adult clinical depression as models of childhood and adolescent clinical depression. Specifically, we propose to assess the usefulness of the forced-swim test and of learned helplessness as animal models for clinical depression in juvenile rats. The key questions which are addressed by this proposal are: 1) Do juvenile rats respond to antidepressant drugs with decreased immobility in the forced swim? 2) Do juvenile rats develop learned helplessness after inescapable stress in both the acute and persistent paradigms, as demonstrated by shuttlebox testing? 3) Do juvenile rats respond to antidepressant drugs in the both acute and persistent learned helplessness paradigms with decreased escape latencies in shuttlebox testing? Ultimately, the models may facilitate a better understanding of the underlying neurobiology of clinical depression, and serve as predictive measures of antidepressant efficacy in children and adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIDEPRESSANT SCHIZOPHRENIA
AUGMENTATION
OF
LATE
LIFE
Principal Investigator & Institution: Kasckow, John W.; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: Depressive symptoms in schizophrenia, while highly prevalent, often chronic, and disabling, remain relatively understudied. Antidepressants are commonly used in clinical practice to treat a variety of symptoms in patients with schizophrenia. Although some literature describes the treatment of syndromal depression in primarily young adults with schizophrenia, comparatively little research is available to guide the treatment of subsyndromal depressive symptoms in this population, especially in
Studies
9
middle-aged and older adults with schizophrenia. Older people with schizophrenia differ from their younger counterparts in several important ways, such as having greater physical comorbidity, cognitive impairment, and a higher risk of side effects. This study will evaluate the efficacy and safety of antidepressant (citalopram) versus placebo augmentation of atypical antipsychotics to treat subsyndromal, residual depressive symptoms in middle-aged and older patients with schizophrenia. This collaborative, two-site (University of California, San Diego and University of Cincinnati), five-year study hypothesizes that citalopram augmentation of antipsychotic medication will be more effective than augmentation with placebo at reducing depressive symptoms and enhancing functioning and quality of life. We propose to enroll a total of 240 outpatients with schizophrenia, who are 55 years or older and have a Hamilton Depression Rating Scale 17-item score of ten or greater, into a randomized, double-blind, flexible-dose, placebo-controlled study. After stabilization for at least four weeks on an atypical antipsychotic agent (either risperidone or olanzapine), patients who have residual depressive symptoms (HAM-D score of ten or greater) will be randomized to one of the following interventions: atypical antipsychotic (risperidone or olanzapine) plus citalopram; or atypical antipsychotic (risperidone or olanzapine) plus placebo. The double-blind treatment period will be three months with a follow-up assessment three months later. Depressive symptoms and side effects will be assessed weekly for the first month, biweekly for the second month, and again at the end of the third month. In addition, we will evaluate cognitive, motor and daily functioning, quality of life, and medication adherence throughout the study. Unique to this proposal, we will use performance-based outcome measures to assess real-world functional capacities. By providing empirical evidence to guide treatment of depressive symptoms in patients with schizophrenia, the study could have significant public health implications for the reduction of disability and the enhancement of quality of life in this patient population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIDEPRESSANT TREATMENT OF MELANCHOLIA IN LATE LIFE Principal Investigator & Institution: Roose, Steven P.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 31-DEC-2003 Summary: (Adapted from applicant's abstract): Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of major depression. However, there is also evidence that SSRIs may be significantly less effective than tricyclic antidepressants (TCAs) for depressed patients with melancholia. This issue is of particular concern in late-life major depression. SSRIs have important safety advantages with respect to overdose and a benign cardiovascular profile. Furthermore, the SSRIs do not have significant anticholinergic effects, and appear to be better tolerated than the TCAs. Perhaps most important, the SSRIs are currently widely prescribed as the medication treatment of first choice for major depression in late-life. Therefore, if it were determined that SSRIs are considerably less effective than TCAs in the treatment of melancholia in the elderly, there would be significant ramifications for clinical practice. Using a randomized, double-blind, parallel group design, the applicants will compare the efficacy and safety of a SSRI (sertraline) and a TCA (nortriptyline) in outpatients over the age of 60 who meet DSM-IV criteria for unipolar major depression, excluding patients who meet criteria for psychotic or atypical subtype. The randomization will be stratified by the presence or absence of melancholia. Outcome measures for the 12-week acute phase will include clinician and patient ratings of symptoms, side effects, and an
10
Antidepressants
evaluation of the health-related quality of life (HRQOL). At the end of the acute treatment phase, patients who meet criteria for clinical response will participate in a 6month continuation phase. The applicants will test the hypothesis that the medication condition interacts with diagnostic subtype (melancholic vs. non-melancholic) in determining antidepressant response. The applicants predict that among melancholic patients nortriptyline will be superior to sertraline in efficacy, whereas among nonmelancholic patients, nortirptyline and sertraline will have equal efficacy. The roles of symptom severity and alternative diagnostic subtyping in contributing to this pattern will be examined. The applicants predict that speed of response will be faster with the TCA, independent of subtype. Failure to show substantial improvement early in treatment may have greater predictive value for final TCA than for final SSRI nonresponse, indicating a need for longer SSRI treatment in the elderly. Finally, The applicants expect HRQOL to show continued improvement during the continuation phase in euthymic patients and an advantage for the SSRI in HRQOL improvement due to a superior side effect profile. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIDEPRESSANT USE BY OLDER ADULTS Principal Investigator & Institution: Blazer, Dan G.; Professor; Psychiatry and Behavioral Scis; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Use of antidepressant medications by older adults has increased significantly over the past 10 years. This increase, however, has not been distributed equally by race/ethnicity. To explore antidepressant use in older adults, we propose additional analyses of data from the Duke Established Populations for Epidemiological Studies of the Elderly (EPESE) sample (4,162 community dwelling elders initially interviewed in 1986 and followed over ten years via three additional in person and four telephone follow-up interviews). Detailed current medication use was obtained from sample members during each in-person interview. In controlled analyses, Whites were two to four times as likely to be taking antidepressant medications as African Americans at each survey and the differences by race increased over a ten year period of follow-up. This difference was especially noted between years six and ten of the follow-up study, with 80% of new users of antidepressant medications over this period being White. We propose a model to determine propensities to use antidepressants in Whites and to test the concordance/discordance of this propensity model in African Americans. This model includes eight domains: demographics; education/occupation/economic well being; geographic characteristics; health and mental health; personal attitudes; social and spiritual resources; health behaviors; and physician provider characteristics. The richness of this model derives from additional questionnaire data, HCFA Part A and Part B files, geocoding the residence of sample members, and detailed descriptions of the physicians listed as their primary providers. Hypotheses are proposed to construct propensity scores among Whites for the eight domains including: 1) there will be a decreased propensity to take antidepressants among participants whose primary source of care is a primary care physician who practices in a rural county; and 2) a perceived impairment in the social network will increase the propensity to use antidepressants. Our main hypothesis is that the propensity model derived for Whites will be discordant for African Americans and the discordance will be found in factors for Personal Mastery, spiritual resources, alcohol and medication use, and racial concordance. We will also test hypotheses specific to individual domains in the larger model.
Studies
11
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CBT FOR RESIDUAL ADHD SYMPTOMS IN ADULTS Principal Investigator & Institution: Safren, Steven A.; Assistant Professor, Harvard Medical Sch; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): This is an amended (third) submission for a NIMH small grant (RO3) to estimate the efficacy of cognitive behavioral therapy for coping with medication-resistant symptoms of Attention Deficit Hyperactivity Disorder (ADHD). The first submission was reviewed quite positively, and, as noted by the set of second reviews, all reviewers' comments were addressed, improving the study design. However, a few new concerns emerged, and despite the improvements, the score was slightly raised. These concerns are fully addressed in this final submission. ADHD in adulthood is a valid, clinically significant, debilitating and prevalent disorder for which there are currently no empirically-validated psychosocial treatments. Although previously thought to be a disorder of childhood, prospective longitudinal data has revealed that ADHD persists in as many as 50% of young adults who were diagnosed in childhood, and that as many as 5% of adults may suffer from this disorder. The combination of core and associated symptoms places persons with this disorder at severe risk for academic and occupational underachievement, relationship difficulties, and significantly-impaired quality of life. Ten years of study by our research team and others -- including controlled studies of stimulant medications and open studies of tricyclic, monoamine oxidase inhibitor, and atypical antidepressants -- reveal that 2050% of adults are considered nonresponders due to insufficient symptom reduction or their inability to tolerate these medications (Wender, 1998; Wilens et al., 1998a). Moreover, adults who are considered responders typically show a reduction in only 50% or less of the core symptoms of ADHD (Wilens et al., 1998a). This leaves pharmacologically-treated patients with significant residual symptoms which cause functional impairment and may also increase risk for relapse. The current application is to develop and test a skills-building, cognitive-behavioral intervention for adults with ADHD. Interventions will be administered in modules that are matched to domains of impairment characterizing individual patient presentations. The proposed project will lay a foundation for a large scale randomized controlled trial of CBT for residual symptoms of ADHD. The project is to be conducted at Massachusetts General Hospital's Adult ADHD program which provides access to large numbers of patients with ADHD, a strong history of research success, and nationally recognized experts who will serve as mentors for the new investigator PI utilizing the R03 mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CELLULAR PSYCHOPHARMACOLOGICAL MONITORING SYSTEM Principal Investigator & Institution: Ludvig, Nandor; Associate Professor; Plastics One, Inc. 6591 Merriman Rd Sw Roanoke, Va 24018 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 31-DEC-2001 Summary: A novel cellular pychopharmacological monitoring system was developed (patent pending) for research in freely moving animals. The system is built around a miniature air-controlled minivalve. This device can be placed on the head of the animal and is able to drive either a control solution or a drug solution into the brain via a microelectrode-coupled microdiaysis probe. The short distance between the minivalve and the microelectrode/microdialysis probe unit allows to deliver drugs into the brain
12
Antidepressants
rapidly and to record the drug-induced cellular electrophysiological changes instantly. The minivalve is activated remotely by air with a controller. The control solution, the drug solution, the waste fluids, the microdialysis fluids, and the air that activates the minivalvel pass through a 8-channel swivel. This swivel is connected to a 18-channel electrical commutator. The swivel/commutator unit is rotated by a torque-sensitive servo driver and is connected to the minivalve and the microelectrode/microdialysis probe unit via a special cable. The system is completed with an electrical signal distributor to make the electrophysiological data acquisition convenient. The entire monitoring system, that includes the minivalve, the minivalve-controller, the servorotated swivel/commutator unit, the special cable, and the electrical signal distributor will be available in 2001 as a single, easily usable package, at a price of approximately $13,000. The minivalve can be carried by rats, mice, and larger animals on their head, without disturbing their behavior. Since this system enables the investigator to quickly test the cellular electrophysiological effects of many drugs in brain in natural circumstances during behavior, the technology opens up new possibilities for studying drug actions in the central nervous system. As such, the developed system will likely be widely used in the academia and the pharmaceutical industry. PROPOSED COMMERCIAL APPLICATION: 1. In the academia, neuropharmacologists and psychopharmacologists can use the minivalve-system to map the in vivo cellular electrophysiological effects of various well-established drugs, such as sedatives, antidepressants, cognition enhancers, antiepileptics, etc., in the brain of both normal animals and animal models of CNS disorders. 2. Also in the academia, cell biologists, molecular biologists and pharmacologists can use the minivalve system to obtain new information on the role of various neurotransmitters, ion channels, second messengers and genes in the regulation of neuronal electrical activity in the animal brain, during such behaviors as learning, sleep, eating, drinking, sex, etc. 3. In the pharmaceutical industry, researchers can use the minivalve- system to document how their company s new compounds act on the neurons of the animal brain, in vivo. 4. Also in the pharmaceutical industry, researchers can use the minivalve- system to recognize the beneficial cellular electrophysiological effects of their experimental compounds on the electrical activity of neurons in the animal brain, in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTRAL BETA ADRENERGIC RECEPTORS Principal Investigator & Institution: O'donnell, James M.; Professor; Pharmacology; University of Tennessee Health Sci Ctr Health Science Center Memphis, Tn 38163 Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 31-JUL-2003 Summary: (Adapted from the Investigator's Abstract) The proposed experiments will examine mechanisms by which central beta-1 adrenergic receptors are involved in the mediation of antidepressant activity. Based on the results of previous work, four specific hypotheses are proposed. First, it is hypothesized that beta-1 adrenergic receptors are important mediators of antidepressant-like effects observed in behavioral models. Second, it is hypothesized that repeated treatment with antidepressants, particularly those that directly affect noradrenergic systems, results in sustained or enhanced stimulation of central beta-1 adrenergic receptors. Third, it is hypothesized that alpha-1 adrenergic receptor stimulation and Type 4 phosphodiesterase (PDE4) inhibition potentiate antidepressant-like behavioral effects mediated by beta-1 adrenergic receptors. Fourth, it is hypothesized that antidepressant-like behavioral effects mediated by central beta-1 adrenergic receptors are resistant to tolerance development. These hypotheses will be tested using two behavioral models.
Studies
13
Discrimination of centrally administered isoproterenol will provide an index for assessing stimulation of central beta-1 adrenergic receptors in vivo. Behavior maintained under a differential-reinforcement-of-low-rate (DRL) schedule will be used to assess antidepressant-like behavioral effects. First, the ability of antidepressants from different pharmacological classes to substitute for the discriminative stimulus effects of centrally administered isoproterenol will be determined. Second, this behavioral model will be used to assess the functional state of noradrenergic neurons/beta-1 adrenergic receptors following repeated treatment with antidepressants. Third, the manner by which alpha-1 adrenergic receptor stimulation and PDE4 inhibition alters the antidepressant-like effects on DRL behavior resulting from beta-1 adrenergic receptor stimulation will be examined. Fourth, the persistence of antidepressant-like behavioral effects mediated by beta-1 adrenergic receptors will be assessed. The results of the proposed experiments will elucidate mechanisms mediating antidepressant effects associated with central beta-1 adrenergic receptors and will begin to identify receptor and post-receptor mechanisms that can be targeted pharmacologically to produce or augment antidepressant activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CGX-1160, A NON-OPIOID, BROAD-SPECTRUM ANALGESIC Principal Investigator & Institution: Wagstaff, John D.; Cognetix, Inc. 421 Wakara Way, Ste 201 Salt Lake City, Ut 84108 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-JUL-2002 Summary: (provided by applicant): The goal of this proposal is to establish the efficacy of contulakin-G (CGX-1160), a newly discovered analgesic conopeptide for the treatment of chronic pain. Currently chronic pain is treated with a variety of analgesic and adjuvant drugs including: opioids, tricyclic antidepressants, anticonvulsants, and local anesthetics. A significant number of patients, particularly those suffering from neuropathic pain, are refractory to all of the currently available drugs. Furthermore, all of these compounds have significant, dose- and treatment-limiting side effects. Preliminary data suggest that CGX-1160 is an extremely potent analgesic in animal models of persistent pain following intrathecal administration, with a wide separation between efficacy and toxicity, and may represent an alternative therapy for intractable pain. In phase I we will demonstrate the efficacy of CGX-1160 in a broad range of animal pain models including: acute, persistent inflammatory, chronic inflammatory, and neuropathic pain. A series of closely related analogs will be synthesized and compared to the native conopeptide for their in vivo efficacy, and resistance to endogenous peptidases. We will attempt to determine the specific mechanism of action through in vivo and in vitro pharmacological methods. We will also compare the toxicity profile of this compound with morphine. These studies will determine a behavioral therapeutic index for the compounds tested. This will determine which of the analogs will be further characterized in formal toxicology testing. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CITALOPRAM AUGMENTATION IN OLDER SCHIZOPHRENIA PATIENTS Principal Investigator & Institution: Zisook, Sidney; Professor & Director; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, Ca 92161 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006
14
Antidepressants
Summary: Depressive symptoms in schizophrenia, while highly prevalent, often chronic, and disabling, remain relatively understudied. Antidepressants are commonly used in clinical practice to treat a variety of symptoms in patients with schizophrenia. Although some literature describes the treatment of syndromal depression in primarily young adults with schizophrenia, comparatively little research is available to guide the treatment of subsyndromal depressive symptoms in this population, especially in middle-aged and older adults with schizophrenia. Older people with schizophrenia differ from their younger counterparts in several important ways, such as having greater physical comorbidity, cognitive impairment, and a higher risk of side effects. This study will evaluate the efficacy and safety of antidepressant (citalopram) versus placebo augmentation of atypical antipsychotics to treat subsyndromal, residual depressive symptoms in middle-aged and older patients with schizophrenia. This collaborative, two-site (University of California, San Diego and University of Cincinnati), five-year study hypothesizes that citalopram augmentation of antipsychotic medication will be more effective than augmentation with placebo at reducing depressive symptoms and enhancing functioning and quality of life. We propose to enroll a total of 240 outpatients with schizophrenia, who are 55 years or older and have a Hamilton Depression Rating Scale 17-item score of ten or greater, into a randomized, double-blind, flexible-dose, placebo-controlled study. After stabilization for at least four weeks on an atypical antipsychotic agent (either risperidone or olanzapine), patients who have residual depressive symptoms (HAM-D score of ten or greater) will be randomized to one of the following interventions: atypical antipsychotic (risperidone or olanzapine) plus citalopram; or atypical antipsychotic (risperidone or olanzapine) plus placebo. The double-blind treatment period will be three months with a follow-up assessment three months later. Depressive symptoms and side effects will be assessed weekly for the first month, biweekly for the second month, and again at the end of the third month. In addition, we will evaluate cognitive, motor and daily functioning, quality of life, and medication adherence throughout the study. Unique to this proposal, we will use performance-based outcome measures to assess real-world functional capacities. By providing empirical evidence to guide treatment of depressive symptoms in patients with schizophrenia, the study could have significant public health implications for the reduction of disability and the enhancement of quality of life in this patient population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONSUMER INFLUENCES OF TREATMENT OF DEPRESSION Principal Investigator & Institution: Kravitz, Richard L.; Professor and Director; Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): By 2005, the pharmaceutical industry will spend $7.5 billion annually on direct-to-consumer advertising (DTCA) of prescription drugs. Proponents of DTCA say it encourages productive discussions between patients and physicians, while critics charge that it increases unnecessary prescribing, raises costs, and strains the patient-clinician relationship. Empirical evidence for policymaking in this area is lacking. This study will examine the clinical impact of DTCA by conducting an experiment using standardized patients (SPs) who present with depressive symptoms (representing either major depression or adjustment disorder) and make either: 1) an ad-driven request for a brand-name antidepressant, 2) a generic request for treatment, or 3) no request. Our focus on depression is justified by the high prevalence
Studies
15
and costs of this condition, its relevance to general medical practice, the ubiquity of depression-related DTC ads in both broadcast and print media, and the broadening indications for the use of antidepressant medications. The application has 3 specific aims: 1) to estimate the effects of DTC ad-driven requests on physicians' prescribing of antidepressants for patients with depressive symptoms; 2) to determine whether DTC ad-driven requests are associated with better or worse quality of care in primary care settings; and 3) to describe differences in physicians' communication behaviors when they are confronted by patients making ad-driven requests, generic requests, and no specific requests. In this randomized trial, 144 primary care physicians in 3 U.S. cities will each see 2 unannounced SPs. The SPs will be trained to portray 6 different roles, generated by crossing 2 clinical presentations (major depression and adjustment disorder) with 3 request conditions (DTCA activated, generically activated, and no request). Visits will be audio-recorded, and SPs will record physicians' clinical behaviors. Using multi-level mixed effects models, data will be analyzed to assess the influence of DTCA on antidepressant prescribing and the clinical process of care. These analyses will be supplemented by qualitative and quantitative analyses of physician communication behaviors across experimental conditions. The results will address a pressing policy question (i.e., should DTCA be further regulated?) while also contributing to our understanding of the social influences on diagnosis and treatment of depression in primary care settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROLLED TRIAL OF SERTRALINE FOR DEPRESSION AFTER TBI Principal Investigator & Institution: Bombardier, Charles H.; Rehabilitation Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-MAY-2005 Summary: Persons with traumatic brain injury (TBI) experience high rates of depression, especially during the first six months following their injuries. Neurological and psychosocial factors appear to contribute to depression in this population. Depression following TBI is associated with poor cognitive, behavioral, and functional outcomes. Preliminary studies suggest that people with TBI and major depression may not respond to antidepressant treatment in the same way as depressed persons without TBI, post TBI depression may respond well to selective serotonin reuptake inhibitor (SSRI) antidepressants, that and effective antidepressant treatment is associated with improvements in health status, neuropsychological function, and post-concussive symptoms. No large randomized placebo-controlled studies have been conducted and basic questions remain about the treatment and outcomes of major depression among persons with traumatic injury. As a consequence, depression is not usually assessed after traumatic brain injury, and optimal rehabilitation guidelines for identifying and treating depression have not been established. To address this gap, the proposed study would follow a large consecutive sample of persons hospitalized for moderate to severe TBI to identify those who develop major depression. With those who develop major depression, a 12-week, randomized, double-blind, controlled trial of sertraline would be conducted. The trial would test the hypothesis that sertraline reduces depression related symptoms, as measured by the Hamilton Rating Scale for Depression. Secondary hypotheses to be tested include whether sertraline leads to greater improvement in neuropsychological test performance, post-concussive symptoms and self-reported health status as measured by the SF 36. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
16
Antidepressants
•
Project Title: CORE--PK/PD/PG MODELING Principal Investigator & Institution: Devane, C L.; Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The Pharmacokinetics/Pharmacodynamics (PK/PD) Core (Core B) provides mathematical modeling of datacollected in the three major projects. Core A contributes to the objectives of the SCOR by providing both data analysis and patient specific pharmacogenetic data to develop and test models describing the dose/ concentrationeffect relationships of antidepressants (AD) and antiepileptic drugs (AED) used during pregnancy. For most drugs, pharmacokinetic and pharmacodynamic information is or at least should be the scientific basis for their clinical use. In pregnancy, the dynamic physiological changes that occur in the maternal/placental/fetal unit influence the processes of drug absorption, distribution and elimination leading to varying drug dosage requirements and uncertainty about the extent and consequences of fetal drug exposure. Through population pharmacokinetic modeling, we will identify sources of inter and intraindividual variability in the concentration/time course of AD and AED from the administration of a certain dose. Fetal drug exposure will be predicted using maternal/umbilical cord concentrations obtained at birth. Covariables will be identified and rank ordered for importance that influence this exposure. A variety of effect measures corresponding to the primary disorder for which the AD and AED are being administered will be incorporated into the modeling process. These data analyses in Projects 1 & 2 will be complemented by animal experiments in Project 3 in which access to tissue drug concentrations unavailable in humans should allow further insight into factors influencing fetal drug exposure. Core A will apply the three major categories of pharmacokinetic models, compartmental, physiological and statistical, along with direct and indirect pharmacodynamic models, to explain and predict the role of maternal drug exposure to health and pregnancy outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING Principal Investigator & Institution: Lakoski, Joan M.; Professor; Pharmacology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: Depressive disorders are linked to impairments in the regulation of glucocorticoid and serotonin (5-HT) systems. Examination of depression in the elderly patient has revealed a role for the interaction of the adrenal hormone corticosterone and 5-HT receptors and may also underlie deficits in memory, learning and losses in ability to adapt to stress with aging. Our long term goal is to understand corticosterone and 5HT receptor interaction in the aging hippocampus and provide new clinical approaches for improving the treatment of depression and memory loss in geriatric patients. Using a corticosterone treatment paradigm, we will test the hypothesis that the cellular pharmacological characteristics of the 5-HT1A receptor subtype, as modulated by corticosteroids in the hippocampus, change with aging and loose responsiveness to this hormone, including losses in signal transduction. Electrophysiological, neurochemical and molecular biological approaches will be utilized in the female Fischer 344 rat (3, 12 and 18 mo) under several conditions of corticosterone hormone exposure (adrenalectomy plus low, moderate and high concentrations of hormone replacement) sham adrenalectomy or intact treatment. Aim 1 will utilize in vivo extracellular
Studies
17
recording techniques in the chloral hydrate anesthetized rat chronically treated with corticosterone and evaluate neuronal responses to selective 5-HT1A receptor agonists with aging. Aim 2 will establish the effect of chronic corticosterone exposure on binding and gene expression characteristics of the 5-HT1A receptor in the aging hippocampus using radioligand binding, quantitative autoradiography and in situ hybridization techniques. Aim 3 will address signal transduction in the aging hippocampus mediating corticosterone and 5-HT receptor interactions. Chronic corticosterone administration effects on G protein levels will be examined by Western blot techniques and compared with assessment of age- associated declines in 5-HT1A receptor-mediated G proteincoupling. The results of these studies may lead to an indication that specific glucocorticoid antagonists may facilitate the onset of therapeutic efficacy for antidepressants in the elderly via actions at the serotonergic system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CRYSTAL PHOSPHODIESTERASE
STRUCT.
OF
CYCLIC
NUCLEOTIDE
Principal Investigator & Institution: Ke, Hengming; Associate Professor; Biochemistry and Biophysics; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) Cyclic nucleotide phosphodiesterase (PDE) catalyzes the hydrolysis of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) to produce, respectively, 5'-AMP and 5'-GMP. PDE is a key enzyme to control cellular concentrations of cAMP that is known as "second messenger" and mediates the response of cells to a wide variety of hormones and neurotransmitters. Ten families and twenty two subtypes of human PDE have been identified. The mRNAs of the 22 subtype PDEs are further spliced to generate over 60 isoforms of PDE. The distinct isoforms of PDE are located in different cellular compartments and possess different specificity of substrate. These two features of PDE have attracted great attention from pharmaceutical companies in the past decade. Many selective PDE inhibitors have been studied as therapeutic agents such as cardiotonic agents, vasodilators, antiasthma, atithrombic compounds, smooth muscle relaxants and antidepressants. For example, VIAGRA, an inhibitor of PDE5, is a prescription drug for erectile dysfunction of male patients. This proposal aims at characterization of substrate specificity and inhibitor selectivity by the approach of crystallography. The specific aims are to determine crystal structures of PDEs and their complexes with inhibitors including (1) the catalytic domain of PDE4B, (2) the catalytic domain of PDE4B complexed with the inhibitors rolipram and iodonated cAMP, (3) full length PDE4D and its complexes with the inhibitors rolipram and denbufylline and (4) the catalytic domain of PDE3 and its complex with cilostamide. The structures in this proposal will reveal the details of inhibitor binding at the active site and provide insight into catalytic mechanism. Docking cGMP into the active site of PDE4B, together with the structure of PDE4B-cAMP analog, will shed light on the substrate specificity. Comparison of the structures of PDE-inhibited complexes will shed light on the selectivity of inhibition of different families of PDE, and thus provide a structural basis for design of selective drugs. The structures will be determined by multiple isomorphous replacement, multiwavelength anomalous diffraction, or molecular replacement. The structural models will be built with the program O and refined by the program CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
18
Antidepressants
•
Project Title: DA-NE INTERACTION IN DRUG ABUSE Principal Investigator & Institution: Shi, Wei-Xing; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: The reinforcing property of d-amphetamine and related psychostimulants has been attributed to their ability to block dopamine (DA) uptake and to increase DA release. Through the same mechanisms and by affecting feedback pathways of DA neurons, these drugs also inhibit DA cell firing. However, when DA-mediated feedback inhibition is blocked, d-amphetamine is found to powerfully excite DA cells, in part, through adrenergic alpha1 receptors. Thus, d-amphetamine produces two opposite effects on DA cells mediated by DA- and non-DA mechanisms, respectively. The nonDA-mediated excitation is mimicked by all psychostimulants tested and not by antidepressants, suggesting that it may have an important role in behaviors induced by psychostimulants. To further understand the significance of the non-DA effects, especially the alpha1-mediated increase in DA cell bursting, two series of studies are proposed. The first series will investigate further the mechanisms through which the alpha1 effect is produced by d-amphetamine. Selective antagonists will be used to identify the alpha1 receptor subtype responsible for the effect. DA neurons will be recorded in slices to confirm that the effect is not due to activation of alpha1 receptors on DA cells. Both in vivo and in vitro techniques will be used to test whether the effect involves areas, such as the prefrontal cortex and the raphe nucleus, known to express alpha1 receptors and to project to DA cells. The second series of studies will assess how the alpha1-mediated excitation may contribute to the acute and chronic effects of damphetamine on DA cells. The alpha1 effect will be blocked to see whether the blockade enhances the ability of d-amphetamine to inhibit DA cells. The response of DA cells to d-amphetamine will be examined in non-anesthetized rats to determine whether chronic treatment with d-amphetamine converts the response from an inhibition to an excitation, as reported previously. Studies will be carried out to further determine whether the conversion occurs with a time course parallel the development of behavioral sensitization and whether the excitation is alpha1-mediated. The proposed work will provide crucial information for a complete understanding of how psychostimulants may act through central DA neurons to produce their behavioral effects and may also provide information leading to the development of novel and effective treatments for drug abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: DEPRESSION AND HEALTH OUTCOMES IN REFRACTORY EPILEPSY Principal Investigator & Institution: Gilliam, Frank G.; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 24-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Epilepsy is the most prevalent disabling neurologic illness, and depression is the most frequent comorbid condition associated with epilepsy. The prevalence of depression is 20-50 percent in patients with uncontrolled seizures. This combination affects between 250,000 and 450,000 people in the United States. Our recent clinical studies have shown that depression is a strong predictor of function and health outcomes in epilepsy. Despite the marked adverse effects and high prevalence of depression in epilepsy, most affected patients are not treated. This complacency toward treatment may result from insufficient use of diagnostic screening,
Studies
19
the widespread belief that antidepressants lower the seizure threshold, or lack of demonstrated efficacy in the only controlled trial of antidepressant medications in epilepsy. The broad aims of this study are to define the benefits of antidepressant treatment on mood, compliance, and health outcomes in epilepsy patients with comorbid major depression. Based on our prior clinical and research experience, we hypothesize that 1) pharmacotherapy or psychotherapy will reduce depression and improve health-related quality of life in patients with refractory epilepsy, 2) antiepileptic medication compliance will improve after reduction of depression, 3) seizure frequency will not significantly increase during treatment with a selective seratonin reuptake inhibitor compared to psychotherapy, and 4) depression and antiepileptic medication toxicity are stronger predictors of health-related quality of life than seizure frequency or severity in patients with refractory epilepsy. The hypotheses will be tested through a randomized trial comparing the efficacy of sertraline (n=127) to cognitive behavior therapy (n=127) for mood and health outcomes in patients with refractory epilepsy and depression. Reliable and valid measures will be used to assess depression and healthrelated quality of life. Electronic, computer-assisted monitoring will determine compliance. Multivariate repeated-measures analyses will be used to determine the interrelationships of treatment, mood, antiepileptic medication toxicity, seizure frequency and severity, compliance and health-related quality of life. We anticipate that dissemination of the results of a positive study will support the modification of the current model of intervention for epilepsy from predominantly seizure reduction to a more comprehensive approach that includes assessment and treatment of depression Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION AND IMMUNITY: BEHAVIORAL AND CNS MECHANISMS Principal Investigator & Institution: Friedman, Elliot M.; Psychology; Williams College Williamstown, Ma 01267 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Most investigators hypothesize that immunological abnormalities that have been identified in depressed individuals are secondary to alterations in brain function, particularly in regions and systems that are implicated in the regulation of immune function. Nonetheless, this hypothesis has not been broadly tested despite evidence that immune function is normalized by antidepressant treatment in clinical populations. The proposed research will use the Flinders Sensitive Line (FSL) genetic rat model of depression to test the hypothesis that alterations in brain monoaminergic systems contribute to depression-related abnormalities of immune function. This project builds on exciting recent data showing markedly reduced in vivo type 1 immune responses in FSL rats. Two specific aims comprise the proposed research. The first stems from previous work showing that chronic antidepressant treatment with tricyclic or serotonin-specific antidepressants normalizes behavioral and neurochemical abnormalities in the FSL rats. In the proposed studies, FSL and control rats will receive chronic treatment with the antidepressants desipramine and sertraline. These treatments are expected to normalize behavioral and immunological abnormalities in the FSL animals. The second aim will test the hypothesis that chronic intracerebroventricular infusion of norepinephrine or serotonin, the pharmacological targets of desipramine and sertraline, respectively, will normalize behavioral and immunological differences between the FSL and FRL strains. These experiments will simultaneously evaluate (a) the site of action for antidepressant effects on behavior and hypothesized effects on immune function (i.e. central or peripheral), (b) the extent to
20
Antidepressants
which a specific monoaminergic system may play a greater role in regulating type 1 immune responses, and (c) the immunomodulatory effects of chronic elevations in brain monoamines. Collectively, these studies build on exciting new data, and they are designed as initial steps in the process of describing a seamless chain of influence originating in the brain and culminating in altered function of specific immunological cells. Because the FSL rat has already been established as a valid model for depression, the data generated from these studies promise to illuminate the integrated biological processes that produce increased vulnerability to physical illness in the clinically depressed Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSIVE STATE AND CELL RESISTANCE TO STRESS IN CANCER Principal Investigator & Institution: Revskoy, Sergei; Psychiatry and Behavioral Scis; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 05-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Major depression is frequently co-morbid with cancer. The biological component of this relationship has not yet been established and depression is essentially viewed as a factor that primarily affects quality of life in cancer patients. Whether the influence of the states of depression goes beyond their effect on the quality of life and directly affects molecular and cellular mechanisms of resistance to tumor growth remains to be established. Here we propose a novel approach, which would investigate the effect of clinical depression and its reversal on factors that control the response to antitumor therapy and ultimately tumor progression and outcome of the disease. In particular, we propose to study factors that modify vulnerability of normal cells to genotoxic stress during reversal of the depressive state in breast cancer patients with prior history of chemotherapy and/or irradiation. We will focus on two of the targets most vulnerable to genotoxic stress, leukocytes and hematopoietic progenitor ceils which not only constitute the immune system but also contribute to natural resistance to tumors and are involved in cellular homeostasis in general. The susceptibility of these cells to apoptosis will be evaluated by the expression profiling of apoptosis-related genes and the corresponding proteins. We will also investigate the putative effect of plasma factors in depressed subjects on the signal transduction machinery involved in the cell response to environmental stress which will be determined by screening plasma samples in various specially designed cellular reporter systems in vitro. As a pilot project, this proposal is limited to reversal of the depressive state by pharmacotherapy as the most rational approach for a short term/moderate budget study. The data generated in this study will be applied to a larger project focused on the effect of non-pharmacological therapy for depression in comparison with conventional antidepressants on susceptibility of normal cells to environmental stress. This will provide insight as to whether biological changes at the cellular level are caused by the modulation of specific neurochemical and neuroendocrine pathways which are targeted by conventional antidepressants or by as yet unidentified putative factors that constitute biological features of the depressive state in cancer patients. The results of this study may provide justification for consideration of mood-modifying therapy as an adjuvant therapy in cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
21
Project Title: DRUG INTERACTIONS Principal Investigator & Institution: Rettie, Allan E.; Professor and Chair; Medicinal Chemistry; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-AUG-1983; Project End 31-JUL-2008 Summary: (provided by applicant): Metabolically-based drug-drug interactions are a major cause of morbidity and mortality in the therapeutic treatment of disease. Although significant advances have been made in our understanding of the etiology of such adverse drug reactions, quantitative prediction of these events at early stages of drug development and clinical use remains elusive. This Program Project Grant focuses on understanding the in vitro to in vivo relationships for drug-drug interactions involving the human cytochrome P450 family of enzymes and drug transporters. In the current proposal, we will investigate several emerging factors that complicate our ability to accurately predict changes in drug metabolizing enzyme and drug transporter activity that result from the co-administration of multiple interacting species; (i) nonhyperbolic kinetics and cooperative ligand binding to human P450s, (ii) sequential oxidative metabolism and the formation of metabolic-intermediate (MI) complexes, (iii) the variable contribution made by Type II binding to inhibitor Ki, (iv) the role(s) of drug transporters such as the human OCTs, MDRs and MRPs, and (v) the interplay of drugmetabolizing enzymes and drug transporters in drug interactions associated with induction mechanisms. In Project 1 we will synthesize novel high affinity inhibitors for human CYP2C enzymes and combine this with site-directed mutagenesis studies to enable construction of discriminating computational and structural models for the prediction of inhibitor Ki. In Project 2, we will explore the mechanistic basis for 'allosteric' kinetic behavior with CYP3A4, towards a variety of ligands including caffeine, acetaminophen, pyrene and hypericin using fluorescence and NMR-based approaches. In Project 3, we will explore reasons for the discrepancy between in vivo and in vitro Kis for the test compounds, itraconazole and fluvoxamine and develop new kinetic models for sequential metabolism and MI complex formation with macrolides and antidepressants. In Project 4 we will determine the molecular and genetic factors that influence, both in vivo and in vitro, the magnitude and spectrum of human P450 enzymes and drug transporters induced by the anti-HIV protease inhibitors, nelfinavir and ritonavir. Collectively, these studies should provide new conceptual and practical tools to achieve quantitative predictions of drug-drug interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: DRUG TREATMENT OF DEPRESSION IN THE NURSING HOME AGED Principal Investigator & Institution: Katz, Ira R.; Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-1993; Project End 31-JUL-2008 Summary: (provided by applicant): US nursing homes (NH), with their 1.6 million residents, are important sites for the delivery of mental health services as well as for research on the care of the larger group of older, chronically ill, and disabled individuals. With their multiple chronic illnesses and complex medication regimens, NH residents are at high risk for morbidity related to both depression and the side effects of antidepressants (AD). Although treatment is efficacious, even in NH residents, there are concerns that AD, including Serotonin Reuptake Inhibitors (SSRI's), can lead to significant adverse events including falls and fractures. This vulnerability must be viewed in the context of ongoing patterns of care. Nationally, more than 1/3 of NH
22
Antidepressants
residents are taking AD. Based on estimates from our research, approximately 14% of cognitively intact or mild-moderately impaired long term care residents have untreated depression, 20% appear to be partially treated, and 26% are taking AD but do not have current depressive symptoms. Most nursing home residents who are depressed are suffering from an initial episode of late life depression, and, therefore, when they go into remission, they do not meet guideline- based recommendations for maintenance treatment. Thus, for substantial numbers of nursing home residents, there are questions about the balance between the benefits of long term treatment with AD's (to prevent recurrences of depression) versus the risks (related to adverse effects including falls, injuries, and fractures). Accordingly, we propose to conduct a partially randomized patient (and provider) preference study for NH residents taking AD's who have been in remission from (at most) a first episode of depression for a period of 6 months or longer. We will randomize 160 individuals who are ambulatory or semi-ambulatory, cognitively intact or with mild-moderate impairment, from multiple nursing homes to continue AD's or to be withdrawn from them under open-label conditions, and to be followed for a period of one year. To improve generalizability, we will also follow otherwise eligible individuals who refuse randomization because they, their families, or providers have a strong preference for one of the conditions. The study is designed to test the hypotheses that continued AD use prevents recurrences, but that it also increases the risk of falls. We will also estimate relevant effect sizes, and, in more exploratory analyses, evaluate the benefits versus the risks of continued AD use with measures of mood, functioning, behavior, gait/balance, and related parameters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ECONOMICS OF FORMULARY DESIGN AND MENTAL HEALTH POLICY Principal Investigator & Institution: Huskamp, Haiden A.; Health Care Policy; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Prescription drugs have become an increasingly important component of mental health treatment and the costs of psychotropic drugs have increased rapidly in recent years. However, there are major gaps in our knowledge about the economics of psychotropic drug treatment. This Mentored Research Scientist Development Award would allow Dr. Haiden Huskamp, a health economist with expertise in mental health policy and economic institutions, to supplement her economic tools with the knowledge and skills needed to conduct clinically-relevant and policysignificant research on the economics of prescription drugs used in the treatment of mental illnesses. The specific aims of this career development proposal are to: 1) develop a greater understanding of clinical decision-making related to the use of psychotropic drugs; 2) acquire basic knowledge of psychopharmacology; and 3) expand knowledge of the important economic institutions influencing the prescription drug market. In this undertaking, Dr. Huskamp will be guided by her sponsor, Richard Frank, PhD, and cosponsors, Andrew Nierenberg, MD, and Ernst Berndt, PhD. Her career development plan includes guided study with Dr. Nierenberg on clinical issues related to treatment decision-making and Drs. Berndt and Frank on economic institutions of the pharmaceutical market, as well as coursework and participation in psychopharmacological "Grand Rounds," relevant seminar series, and professional meetings. Dr. Huskamp will use the knowledge and skills developed through these career development activities to conduct three research projects. The first project examines the effect of generic entry in the class of selective serotonin reuptake inhibitors
Studies
23
(SSRls) on utilization patterns, costs, and market share among antidepressants as well as the competitive response of brand antidepressant manufacturers with respect to drug prices and promotional spending. The second project assesses the economic incentives created by three-tier drug formularies and how these arrangements affect costs, utilization patterns, and adherence to treatment guidelines in a non-elderly population. This project includes an economic welfare analysis of the tradeoffs associated with restrictive formularies. The third project examines the effect of a three-tier formulary on psychotropic drug costs and utilization patterns in a retiree population and explores the impact of formularies on the mental health costs of adding a prescription drug benefit to Medicare and on access to appropriate psychotropic drug treatment under such a benefit. The proposed plan of career development will provide Dr. Huskamp the training, mentoring, time and resources to develop the skills that will put her in a position to lead independent research on the economics of pharmaceutical treatment for mental illnesses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN AND CAM KINASE IV IN THE LIMBIC SYSTEM Principal Investigator & Institution: Cohen, Rochelle S.; Professor; Anatomy and Cell Biology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Clinical studies have shown that estrogen (E2) can ameliorate symptoms of mood disorders in women, including severe depression. The presence of symptoms may represent an abnormal response to normal hormonal changes, thereby implicating contextual factors in the brain in the etiology of these symptoms. Some of these factors include second messenger systems that lead to the production of neurotrophic agents, including brain-derived neurotrophic factor (BDNF). Chronic stress results in deleterious effects on neurons and synapses which, in turn, may be related to alterations in affective behavior. Because of its involvement in cellular and synaptic growth and/or function, BDNF may counteract these negative effects and restore the appropriate behavioral responses. The gene transcription factor cyclic AMP response element-binding protein (CREB), has been shown to be a target of antidepressant and E2 action. Activation of CREB can lead to transcription of the BDNF gene. We propose that the Ca2+/calmodulin-dependent protein kinase IV (CaMK IV) pathway, "CaMK IV - CREB - phosphorylated CREB (pCREB) - BDNF," mediates some of the effects of long-term E2 treatment on behavior. Long-term E2 treatment results in the persistence of these messengers, even after two weeks. E2 may regulate CaMK IV and BDNF via alterations in their mRNAs; we will perform in situ hybridization to address the hypothesis that E2 regulates levels of CaMK IV mRNA and BDNF mRNA. We will also determine if E2 decreases relevant phosphatases, including protein phosphatase 2A and the calcineurin pathway, negative regulators of CaMK IV and pCREB, respectively. To determine if CaMK IV, CREB and/or BDNF mediate E2 effects in the forced swim test, a test for the efficacy of antidepressants in rodents, antisense oligodeoxynucleotides (ODNs) to CaMK IV, CREB or BDNF will be infused into the amygdala or hippocampus and animals will be subjected to the test conditions. Infusion of these antisense ODNs may interfere with the positive effects of E2 on forced swim. We will also determine if infusions of BDNF protein with the antisense ODNs to CaMK IV and CREB reverse the actions of the ODNs on behavior. These experiments will give insight to the molecular effects of E2 in areas of the brain related to affective processing and will uncover mechanisms that may allow hormonal intervention for the amelioration of female-related mood disorders.
24
Antidepressants
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONS OF BIOGENIC AMINE TRANSPORTERS Principal Investigator & Institution: Gu, Howard H.; Pharmacology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-AUG-2003 Summary: (Applicant's Abstract) Biogenic amine transporters are the main targets of cocaine, amphetamines, and antidepressants. My broad, long-term objectives are to understand the functions and mechanisms of these transporters, specifically their roles in the addiction to drugs of abuse and the actions of therapeutic drugs. A Mentored Research Scientist Development Award will allow me to learn new techniques necessary to study the in vivo functions of the biogenic amine transporters and to gain further experience before embarking on a fully independent research program. Biogenic amine transporters have been studied extensively in tissue preparations and cultured cells, and indirectly in whole animals using compounds that block these transporters. The only direct assessment of the roles of the transporters is the recent knockout of dopamine transporter in transgenic mice. Despite the significant new information learned from this study, extensive adaptation changes have set limitations to the study. Therefore, we propose to engineer an inducible antisense suppression system to study the biogenic amine transporters. In this approach, an antisense RNA would be expressed with an improved tetracycline operon based inducible system to suppress a specific transporter in a controllable and reversible manner. We will evaluate the effectiveness of the approach in cultured cells first, and next in transgenic mice. Then we will use this approach to investigate the physiologic and behavioral changes of the animals. We hope to provide new information about the functions of the transporters in whole animals and their roles in the addiction to drugs of abuse and the therapeutic actions of antidepressants. The knowledge gained from these studies may eventually lead to better approach to treat drug addictions, depression and other related diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: GENE EXPRESSION PROFILE OF ANTIDEPRESSANTS Principal Investigator & Institution: Duman, Ronald S.; Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 07-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Depression is characterize behaviorally by depressed mood, inability to experience pleasure, withdrawal of interest, and feelings of worthlessness which can often result in a debilitating quality of life, as well as suicide in many cases. Despite the significant advances that have been made in neurobiology and neuropharmacology of antidepressants, the molecular mechanisms underlying the actions antidepressant treatment have not been identified. Although the acute action of most antidepressants occurs via inhibition of the reuptake or breakdown 5-HT and NE, increased synaptic levels of these monoamines alone cannot account for the therapeutic action of antidepressants. Recent studies have shown that chronic antidepressant treatment (ADT) alters gene expression, especially components of cAMP signal transduction cascade. The delay in the therapeutic effects of ADT coincides with changes in gene expression in intracellular pathways, and it is thought that these changes mediate the therapeutic effects of antidepressants. It is known that stress and antidepressants have opposing actions on neuronal growth and vulnerability, in part due to the opposing effects on expression of neurotrophic factors. We hypothesize that
Studies
25
stress and antidepressant administration have reciprocal changes in gene expression profiles. The aim of this R21 Exploratory Grant is to characterize the gene expression profiles to different classes of ADT, including 5-HT and norepinephrine selective reuptake inhibitors and ECS, and compare these profiles with changes observed with stress. It is however necessary to distinguish between acute and chronic alterations in response to ADT as only chronic ADT has been shown to possess therapeutic effects. This can be accomplished by comparing expression profiles by microarray analysis at various time points after and ADT. Gene expression changes will be characterized in the hippocampus and dentate gyrus of rat brain. This will increase our understanding of the mechanisms underlying the actions of antidepressant treatment and could lead to novel therapeutic targets. The results from these studies should lead to an ROl proposal aimed at extending these findings. Briefly, further studies would involve modulating the expression of genes identified by viral-mediated expression of genes in discrete brain regions and generation of transgenic mice, for study in behavioral models of stress and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF NEMATODE BEHAVIOR Principal Investigator & Institution: Emmons, Scott W.; Professor; Molecular Genetics; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): This research investigates the genetic basis of male sexual motivation and behavior. Behaviors leading to sexual reproduction are essential for the survival of most animal species, yet little is presently known about how the nervous system generates appropriate motivational states and appetitive and consummatory sexual behaviors. One approach to understanding animal behavior is to identify essential genes and study their cellular expression patterns and molecular functions. In order to identify genes required for male sexual behavior, mutants defective in both appetitive and consummatory phases of sexual behavior will be identified in the soil round worm Caenorhabditis elegans, a well-defined invertebrate genetic model organism. Preliminary studies have established a quantitative behavioral assay for a putative mate-searching behavior of the adult C. elegans male. The assay has been used to show that expression of mate-searching behavior is regulated by presence or absence of suitable mates, nutritional status, and signals from the reproductive system. The results are interpreted to indicate that mate-searching is potentiated by a regulated state of the nervous system that we define as the nematode analog of a sex drive motivational state of higher animals. Genetic screens will be performed to identify new mutants of two types: mutants in which males fail to express mate-searching behavior and mutants in which males exhibit sex drive yet fail to copulate. Selective genes identified will be molecularly cloned and the identity and expression patterns of their products defined. Among three mate-searching-defective genetic loci already identified, one encodes the C. elegans homolog of the serotonin reuptake transporter, the target in both humans and nematodes of fluoxetine antidepressants. In view of the sexual dysfunction caused by fluoxetine administration in humans, this result suggests that these studies may have relevance to understanding motivated sexual behavior in humans and thus may have potential clinical implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
26
Antidepressants
•
Project Title: GENETIC DISTRUPTION IMPLICATION FOR DEPRESSION
OF
MONOAMINE
SYSTEMS:
Principal Investigator & Institution: Caron, Marc G.; Professor and Hhmi Invesitgator; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Depression is a psychiatric disorder where a disturbance of mood is the prominent feature. Although the etiology of depression is unknown, alterations in serotonergic and noradrenergic function have been clearly implicated in the disorder. The present Center Grant proposes to examine depression from the perspectives of functional imaging, morphometrics, and pharmacological interventions in humans, as well as through the use of a variety of animal models of depression. The overall objective of the mouse studies is to show how the serotonin (5HT) and norepinephrine (NE) systems are interdependent in the development and amelioration of symptoms of depression and to reveal the neural mechanisms that contribute to this reaction. In Aim I, the role of the monoamines will be investigated in the heterozygous vesicular monoamine transporter 2 (VMAT2) animals. Studies will be performed to determine whether antidepressants influence monoamine levels in selected brain regions and whether these alterations are related to responses in several different behavioral models of depression. An inducible VMAT2 knockout (KO) mouse will be developed so that the role of this gene and subsequent alterations in neurochemical and behavioral responses can be readily assessed. In Aim II, the role of the norepinephrine transporter (NET) in depression will be evaluated. Experiments will be conducted in NET-KO mice to examine the effects of antidepressants on brain monoamines and behavior. An inducible NET-KO mouse line will be developed such that the role of this gene in the prevention of depression can be evaluated at any time. In Aim III, effects of 5-HT dysfunction will be studied in mice by selectively restoring VMAT-2 function to catecholaminergic neurons in the VMAT2-KO line. In this case, 5HT and histamine function should be defective. We have generated these mice and plan to create an inducible mouse line for additional studies where disruption of VMAT2 function in 5-HT neurons can occur at the discretion of the investigator. The results from the studies in Project 4 will complement the aims of the other Center projects and they will be coordinated with the clinical Projects to better understand the mechanisms that may underlie depression. Additionally, results from the clinical Projects will be integrated into the mouse Project such that, an attempt will be made to examine some of these same phenomena in mice. From these perspectives, the findings from the mouse studies should be helpful revealing some of the molecular, cellular, and biochemical changes that accompany depressive-like behaviors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIV IN WOMEN: DEPRESSION AND IMMUNITY Principal Investigator & Institution: Evans, Dwight L.; Professor and Chair; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Psychiatric morbidity has been associated with HIV disease since the beginning of the AIDS epidemic. Most of the clinical literature to date has focused on psychiatric issues in men who are HIV seropositive. There has been little data regarding the prevalence of psychiatric disorders in HIV infected women, despite the fact that HIV remains among the leading causes of death for US women between the ages of 25 and 44. HIV also is the leading cause of death among African American
Studies
27
women in this age group. We found that the proportion of women with current major depression was four times higher in HIV positive women compared to HIV seronegative women. This high rate of major depression coupled with the recent and largest epidemiology study to date indicating that depression is associated with increased mortality in HIV-infected women, underscores the need for studies to ascertain the relationship of major depression, immunity, and HIV disease progression in HIV infected women. The potential immune mechanisms by which depression may influence HIV disease progression and mortality remain to be understood. In our studies of HIV infected men, we have found depression associated alterations of immune cytotoxic cells suggesting that killer lymphocytes might mediate the effects of depression on HIV disease progression. Although previous studies have focused almost exclusively on HIV infected men, we have recently found that women with depression exhibit significant reductions in natural killer cell activity as well as increases in activated CD8 lymphocytes and viral load. The proposed study of HIV seropositive women, largely of minority representation, is designed to provide important information on 1) the underlying immune mechanisms by which depression my influence HIV-1 replication and thereby HIV disease progression; and 2) three potential mechanisms of action whereby depression my influence immunity and HIV disease progression. The present study may also help determine whether conventional antidepressants (SSRIs) as well as novel antidepressant pharmacotherapies (substance P antagonists and glucocorticoid antagonists) might benefit HIV-infected individuals and extend survival with HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INCREASING TREATMENT ADHERENCE IN CO-OCCURRING DISORDERS Principal Investigator & Institution: Pantalon, Michael V.; Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2007 Summary: (Provided by Applicant): This application is for a "Mentored Patient-Oriented Research Career Development Award" (K23) to study treatment adherence in cooccurring psychiatric and drug use disorders (COD), under the mentorship of Bruce J. Rounsaville, M.D. and Richard S. Schottenfeld, M.D. Nonadherence is a critical issue in COD, especially among those with depressive disorders, as it occurs frequently and limits the maximal benefit achieved by efficacious treatments, particularly those with the potential to improve both conditions (e.g., antidepressants). Therefore, adherenceenhancing interventions for COD can optimize the efficacy of treatments. They are also adaptable to new treatments that are being developed. While preliminary studies indicate that adherence-enhancing interventions are efficacious for patients with nonCOD, little systematic evaluation has occurred in COD. Compared to developing new contents for treatment, studying brief strategies to improve adherence to existing treatments is a highly cost-efficient approach that can have a large and rapid payoff. The research plan for this K23 application entails: 1) the evaluation of adherence issues in 9 ongoing studies and 2) completion of a new clinical trial evaluating innovative adherence-enhancing methods for COD in a dual-diagnosis outpatient clinic. This new clinical trial will employ a dismantling design, within which 75 outpatients with cooccurring depressive disorders and drug abuse/dependence (CODDA) will be randomly assigned to: 1) Treatment-as-Usual (TAU), a control condition offering medication management, standard education regarding diagnosis and the importance of adherence, and group counseling, 2) TAU+Adherence Feedback (TAU+AF), in which
28
Antidepressants
patients receive TAU plus computerized feedback on medication and counseling adherence, based on Medication Event Monitoring System (MEMS; Aprex Corporation, Fremont, CA) data and attendance records, or 3) TAU+Motivationally Enhanced Feedback (TAU+MEF), in which TAU plus Motivational Enhancement Therapy and Contingency Management will be added to AF. Primary outcome measures are: 1) rates of adherence to antidepressant medication, as measured by MEMS caps and self-report, 2) rates of counseling attendance, and 3) reductions in illicit drug use, including achievement of abstinence, as assessed by twice-weekly urine toxicology tests and selfreport. Secondary outcomes include reductions in depressive symptomatology and rates of re-hospitalization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSOMNIA INTERVENTION FOR BREAST CANCER SURVIVORS Principal Investigator & Institution: Epstein, Dana R.; None; Arizona State University P.O. Box 873503 Tempe, Az 852873503 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Insomnia is the most common sleep disorder in both the general population and persons with cancer. Many of the sleep characteristics and ineffective insomnia management strategies of patients with cancer are similar to those of persons with insomnia in the general population. Although women with breast cancer appear to have about twice the risk of developing clinically significant levels of insomnia, sleep difficulty has received minimal treatment attention other than pharmacological intervention (e.g. sedatives/hypnotics, antidepressants). There is a paucity of intervention studies addressing the feasibility and efficacy of nonpharmacological treatment for patients most at need and at risk such as breast cancer survivors (BCS). latrogenic, psychological, and developmental factors may contribute to the development of insomnia in BCS and must be considered in the construction and testing of cognitive-behavioral treatment (CBT). The purpose of the study is to pilot test the feasibility (attendance, attrition, adherence to treatment, participant evaluation of treatment) of a multicomponent CBT and the efficacy of CBT for reducing insomnia in BCS. A 2 (group) X 2 (measurement phase) factorial design will be used. Sixty-four breast cancer survivors will be blocked on their type of insomnia (primary or secondary) and randomly assigned within each type of insomnia to one of the two conditions: CBT group or a contact control group. After the screening process, subjects will be assessed at pre-treatment, treatment, and post-treatment. Sleep outcomes will be evaluated using objective (wrist actigraphy) and subjective (daily sleep diaries) measures. In addition, the impact of CBT on the sleep-associated variables of fatigue, mood, and quality of life will also be explored. Descriptive statistics, analyses of covariance, mediational analysis, and regression analysis will be used to examine the data. This feasibility pilot study will provide the basis for a larger study to evaluate efficacy and to examine the effect of the intervention on the quality of survival time and comorbidities among BCS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: DEPRESSION
LONG-TERM
ANTIDEPRESSANT
OUTCOME
IN
BIPOLAR
Principal Investigator & Institution: Ghaemi, S Nassir.; Cambridge Health Alliance 1493 Cambridge St Cambridge, Ma 02139 Timing: Fiscal Year 2001; Project Start 10-FEB-2001; Project End 31-JAN-2006
Studies
29
Summary: (Adapted from the Applicant's Abstract):Summary: This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23) to develop expertise in evaluating, designing and applying research methods for assessing pharmacological treatments for bipolar depression, based on a balanced program of didactic, tutorial, and practical research experiences. The applicant will study the impact of continuing vs. discontinuing antidepressants in a naturalistic, but controlled and randomized, long-term (up to 3 year) clinical study of patients with bipolar disorder who are clinically maintained on mood-stabilizing treatment. The proposal will be completed as part of the national NIMH-sponsored Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) project. Rationale: In contrast to unipolar major depression, bipolar depression is among the least studied depressive illnesses, with very little research on the long-term efficacy or safety of antidepressants used in conjunction with mood-stabilizing agents, or their effect on the course of bipolar disorders, including induction of mania, mixed states, psychosis, or rapid-cycling. Despite these potential risks, the depressive phase of bipolar disorder is sufficiently compelling clinically that antidepressants rather than mood-stabilizing agents are the most commonly used treatments in bipolar disorder, supporting the timelines of the present proposal. It is unknown if these antidepressant treatments are effective or even safe in these circumstances. Environment: The project is based at the Massachusetts General Hospital project site of the NIMH national STEP-BD study of long-term treatment of bipolar disorder, with the collaboration of two other STEP-BD sites. Included are a program of practical training and supervised research under primary mentorship of Ross J. Bladessarni MD, co-sponsorship by Gary S. Sachs MD, and consultation by bipolar disorder expert Frederick K. Goodwin MD and biostatistician John Hennen PhD. Career development plan: Training is designed to assume that the applicant achieves competence in the critical evaluation and design of long-term pharmacological studies in adults with major affective disorders, as well as in applying these skills to the design, conduct, and analysis of a supervised clinical trial. Training includes completion of MPH coursework at the Harvard School of Public Health and tutorials on the theory and analysis of research designs and statistical methods for longitudinal studies supervised by the biostatistical consultant in collaboration with the mentor, co-sponsor, and consultants. In this process, the applicant will develop competence to lead independent studies of the long-term treatment of bipolar disorder as a principal investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF DEPRESSIVE BEHAVIOR IN WISTAR-KYOTO RATS Principal Investigator & Institution: Tejani-Butt, Shanaz M.; Pharmaceutical Sciences; University of the Sciences Philadelphia in Philadelphia Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-JUN-2001; Project End 31-MAY-2004 Summary: (provided by applicant): The Wistar-Kyoto (WKY) rat has been proposed as a useful animal model in which to study the connection between stress responsiveness and vulnerability to depressive behavior. Physiologically, the WKY rat shows greater susceptibility to stress-induced gastric ulcers than other strains. Endocrine studies report that WKY rats have high levels of stress-induced adrenocorticotropin and low levels of corticotropin releasing hormone, suggesting a defective feedback in the hypothalamic-pituitary-adrenal (HPA) axis. Our research has revealed significant differences in central norepinephrine (NE) and serotonin (5-HT) sites in WKY rats when compared to Sprague-Dawley rats. Treatment with desipramine (a NE uptake blocker),
30
Antidepressants
but not paroxetine (a 5-HT uptake blocker), decreased immobility time in the Porsolt forced swim test, and reduced ulcer incidence, implicating the NE system in the mediation of depressive behavior in WKY rats. This grant is aimed at further substantiating the value of the WKY model, and is designed to determine the mechanisms that mediate the disease condition. Differential sensitivity to antidepressants with distinct pharmacological actions may provide useful information regarding the underlying substrates that contribute to a selective response in the WKY rat. Thus the central objective is to ascertain whether antidepressants that target specific neurotransmitter sites in the brain, will alleviate depressive behavior and attenuate the animal's responsiveness to stress. This behavioral response is expected to decrease ulcer susceptibility, modify feedback in the HPA axis, and reverse the characteristic NE and 5HT receptor alterations in the WKY rat. A positive answer to this objective will provide significant information regarding the mechanisms that underlie depressive behavior and ulcer susceptibility in this vulnerable rat strain. The information gained from this study could provide a better understanding of why a clinical response is observed in some populations of depressed patients, while a resistance in treatment response is seen in others. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEDICATIONS FOR COMORBID COCAINE AND ALCOHOL DEPENDENCE Principal Investigator & Institution: Johnson, Rolley E.; Associate Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-OCT-2003 Summary: (provided by applicant): Cocaine abuse and dependence continues to be a major public health problem with up to 3 million people in need of treatment. Over the past decade, medications including dopamine agonists, antagonists, tricyclic antidepressants, selective serotonin reuptake inhibitors, opiate mixed agonistantagonists, and opioid antagonist have been studied for thetreatment of this disorder. No efficacious medication has been found to treat cocaine abusing or dependent patients. The lack of a efficacious medication for cocaine dependence has led to the proposal to treat co-morbid disorders found with high frequency in cocaine abusing patients, especially when these disorders are thought to enhance or perpetuate the use of cocaine. Alcohol abuse/dependence is the most common co-morbid condition found in cocaine abusing patients; as many as 85% of patients with cocaine dependence also have a diagnosis of alcohol abuse or dependence. Since alcohol use is common among cocaine abusers, it is possible that treatment of co-morbid alcohol use could lead to decreases in cocaine use. Disulfiram is approved for the treatment of alcohol abuse. Thus, it is possible to test the hypothesis that treatment of alcoholism in cocaine abusing patients will lead to improvements in cocaine use, as well as alcohol use. Disulfiram inhibits the enzyme that breaks down acetaldehyde (the first metabolite of alcohol) thus causing an increase in acetaldehyde which produces unpleasant aversive effects. It also inhibits opamine P-hydroxylase causing an increase in dopamine and decrease in norepinephrine that may result in attenuation of cocaine craving and euphoria and thus decrease the desire to use cocaine. This may explain the reported reduction in cocaine use in opioid dependent patients treated with disulfiram. Thus, disulfiram appears to have potential for impacting significantly on the treatment of cocaine addicts. This study assesses the efficacy of disulfiram at two different doses levels (62.5 mg and 250 mg) to treat cocaine dependent patients with a dual diagnosis of cocaine dependence and alcohol abuse or dependence. A randomized, placebo controlled, parallel 3-group
Studies
31
design is utilized in conjunction with manual-guided Cognitive-Behavioral Therapy (CBT). Primary outcome measures include: 1) continuous cocaine (qualitative and quantitative) and alcohol abstinence, 2) retention time in treatment, and 3) frequency and quantity of cocaine and alcohol use. Secondary measures include: 1) use of other illicit drugs, 2) side effects data, 3) safety data, 4) self- and observer global reports and 5) other subjective measures (e.g., psychosocial adjustment, time spent in use, reduction in time spent in use, severity of withdrawal, etc.). This study will utilize rigorous clinical trials methodology to provide critical scientific and safety data for assessing disulfiram as a treatment for primary cocaine dependence and associated alcohol abuse and dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEDICATIONS, GENETIC VARIABILITY & BREAST CANCER Principal Investigator & Institution: Newcomb, Polly A.; Member and Acting Head; Laboratory for Cancer Research; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-APR-1992; Project End 31-MAR-2008 Summary: (provided by applicant): Recent evidence suggests that commonly used medications may be determinants of breast cancer risk. In this fourth renewal of our highly successful breast cancer case-control studies, we propose a new project to investigate the relation between breast cancer incidence and the use of non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, and drugs to treat osteoporosis. Specific hypotheses include: 1) regular use of NSAIDs is associated with a decreased risk of breast cancer; 2) antidepressant use is associated with increased risk of breast cancer; 3) use of drugs to prevent or treat osteoporosis is associated with a decreased risk of breast cancer; and 4) these associations are modified by genetic predisposition, specifically in polymorphisms related to the oxidation and glucoronidation of these compounds. To test these and other hypotheses, we will interview 3,564 women under 70 years of age with newly diagnosed breast cancer, identified through Wisconsin's statewide mandatory tumor registry. For comparison, we will interview 3,546 similarlyd female community members selected at random from the population using lists of licensed drivers. Study subjects will be interviewed by telephone regarding their use of the medications of interest and breast cancer risk factors. Participants will contribute buccal cells for DNA to be genotyped for CYP2C9, UGTIA6, and CYP2D6 polymorphisms. We will also bank DNA for future gene-environment studies. Building on existing and long-standing protocols allows us to evaluate the association of these increasingly common exposures with breast cancer risk in an efficient and timely manner. Further study of these modifiable exposures and relevant genotypes will provide more information on which women and their physicians can base decisions regarding behavior and may provide insights into the biology of this common tumor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: METHOD FOR MAKING AN IMPROVED ST JOHN'S WORT PRODUCT Principal Investigator & Institution: Castor, Trevor P.; President & Chief Executive Officer; Aphios Corporation 3-E Gill St Woburn, Ma 01801 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-DEC-2002 Summary: (Adapted from the application): The goal of this Phase I/Phase II Fast Track project is to develop an improved St. John's Wort product which can be manufactured in
32
Antidepressants
a standardized and reproducible manner. St. John's Wort contains multiple bioactive compounds that have been used in a wide variety of ailments, most notably endogenous depression. The approach involves the use of supercritical fluids and near-critical fluids with and without polar cosolvents such as alcohols (trademarked as SuperFluids). These fluids are gases such as carbon dioxide which when compressed exhibit enhanced thermodynamic properties that can be fine-tuned for rapid and selective extraction of bioactive molecules. In Phase I, optimal conditions for selective SuperFluids extraction of and chromatographic purification of St. John's Wort will be established. In preliminary studies, this was accomplished by following the extraction of bioactive compounds with super critical carbon dioxide with 0 to 20% methanol. The results of Phase I studies will be used to develop a large scale manufacturing process. In a Phase II investigation, the conditions for selective extraction and chromatographic purification of bioactive compounds will be further optimized in terms of mechanical components, enhancement devices and operating parameters. Finally, it is proposed to design, build and test a pilot-scale prototype plant that could operate under cGMP conditions. Paracelsian (Ithaca, NY) will perform serotonin uptake assays on contract. PROPOSED COMMERCIAL APPLICATION: Among the most widely prescribed antidepressants in the United States are Prozac from Eli Lilly, Zoloft from Pfizer and Paxil from SmithKline Beecham. The worldwide sales of the top selling antidepressants are approximately $4.8 billion. As people experience adverse side-effects from prescription antidepressants, there has been a concomitant rise in the use of St. John's Wort and other herbs as natural anti- depressants. This Phase I/Phase II Fast Track SBIR project should lead to the development of a biologically-enhanced, stable and standardized St. John's Wort product that can be manufactured under cGMP conditions to provide a natural alternative with reduced side effects of Prozac, Pfizer and Paxil, and thus satisfy a burgeoning market demand in the $4.8 billion antidepressant marketplace. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR AND CELLULAR ANALYSIS OF G PROTEIN FUNCTION Principal Investigator & Institution: Berlot, Catherine H.; Associate Professor; Cellular/Molecular Physiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JAN-1995; Project End 31-MAY-2004 Summary: Heterotrimeric G proteins transmit hormonal and sensory signals received by seven-transmembrane-helix receptors to effector proteins that mediate a wide variety of physiological processes. The importance of G protein signaling pathways in health and disease is underscored by the fact that G protein-coupled receptors are the targets of hundreds of drugs, including antihypertensives, neuroleptics, antihistamines, and antidepressants. An important challenge is to elucidate regulation at the level of how interactions between receptors and G proteins affect their activities and how these interactions are regulated in vivo. An increased understanding of these processes will provide a wider range of targets and strategies for therapeutic interventions for aberrant signaling pathways. The goal of this proposal is to elucidate the mechanism of G protein signaling at both the molecular and cellular levels. The specific aims of this proposal are to answer these questions: (I) What regulates association/dissociation of G proteins and receptors during the activation cycle? The role of a surface- exposed subunit region of alphas in which substitutions increase receptor affinity will be investigated. The critical residues will be localized and the functional effects of mutating them will be determined. Alphas residues in this region will be tested to see if they can confer
Studies
33
specificity for the Beta2- adrenergic receptor. Peptides based on this region will be tested to see if they mimic or block interactions between Gs and the Beta2-adrenergic receptor. (II) Can functionally distinct receptor populations be selectively inactivated by dominant negative alpha subunits? Mutations that both increase receptor affinity and decrease effector affinity will be combined in an effort to produce strong dominant negative alpha subunits. Dominant negative alpha subunits will be used to clarify the physiological roles of receptors that couple to multiple G proteins. (III) How does the cellular organization of receptors and G proteins regulate signaling? Much of what is known about G protein-mediated signal transduction is based on biochemical experiments using purified components and static images of immunohistochemical localization of the proteins in fixed cells. To determine the extent to which these conclusions can be extended to in vivo situations, pairs of proteins (alpha/beta, alpha/receptor, b/receptor) fused to distinguishable GFP mutants will be followed in living cells using time lapse fluorescence microscopy, fluorescence recover after photobleaching, fluorescence resonance energy transfer, and fluroescence correlation spectroscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MECHANISMS OF 5HT RECEPTOR ACTIONS Principal Investigator & Institution: Roth, Bryan L.; Professor; Biochemistry; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-JUL-1996; Project End 31-AUG-2006 Summary: (provided by applicant): This K02 Award will fund the salary support for all of Dr. Roth's research related activities. Three major goals are proposed for this funding cycle including: (1) Characterization of the structure and function of 5-HT2-family serotonin receptors; (2) Discovering the cellular and molecular mechanisms responsible for the regulation of 5-HT2A receptors and (3) Administering the National Institute of Mental Health Psychoactive Drug Screening Program. Characterizing the structure and function of 5-HT2A receptors is of great importance for mental health-related research because a number of psychoactive compounds including atypical antipsychotic drugs, antidepressants and some anxiolytic medications exert their actions via interacting with 5-HT2A receptors. Understanding how such drugs interact with 5-HT2-family receptors at the atomic level may lead to novel insights into drug design and development. Discovering how the 5-HT2A receptor is regulated is important for understanding the pharmacological mechanisms by which drugs may regulate neurotransmitter receptor levels. 5-HT2A receptors are regulated in a paradoxical manner by antagonists and insights into the cellular and molecular mechanisms by which these alterations occur could be of importance for understanding 6-protein receptor coupled regulation. Finally, the NIMH Psychoactive Drug Screening Program is responsible for characterizing the pharmacology of novel psychoactive compounds, some of which may represent new therapeutic agents. A full molecular pharmacologic characterization of these compounds is essential prior to their use in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MOOD AND ANXIETY DISORDERS IN PREGNANCY AND LACTATION Principal Investigator & Institution: Stowe, Zachary N.; Associate Professor and Director; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007
34
Antidepressants
Summary: The treatment of mental illness during pregnancy has gained considerable attention over the past decade. The majority of this attention has focused on antidepressants and major depression, with far less consideration of anxiety disorders and bipolar disorder. The treatment guidelines for mental illness during pregnancy and lactation remain empiric and continue to emphasize the risk/benefit assessment. The lack of data on the course of illness, the impact of pregnancy and lactation of the metabolism and distribution of pharmacological treatments, and the extent of fetal and neonatal medication exposure underscores the empiric nature and prematurity of such guidelines. The current project will enhance and extend the data derived from an ongoing collaborative R01 MH56555-01A2 (Stowe) focused on the relapse of major depression in pregnant women taking antidepressant proximate to conception and K23 MH 63507-01 (Newport) investigating psychosis during pregnancy. We will prospectively follow women with major depression (MID), bipolar disorder (BPD), panic disorder (PD), and obsessive-compulsive disorder (OCD) through pregnancy and the first postpartum year. Many of these women may chose to continue medications such as antidepressants, mood stabilizers, and antipsychotic medications either during pregnancy and/or take medications postpartum. Monthly serum sampling and GCRC admissions will provide novel data.regarding the metabolism, distribution, and fetal/neonatal exposure to these compounds. These PK/PD models will be expanded to include assessment of pharmacogenetic factors of metabolic capacity and protein binding. Similarly, prospective documentation of additional exposures, sex steroid concentrations, and psychosocial variables will further refine such models and provide preliminary assessment of factors (other than medication concentrations) that may influence the course of illness and obstetrical outcome. The current project will utilize the core components to address the deficits in the current literature, affords a diagnostically diverse group of women that may be germane to the results obtained in Project 2 with respect to co-morbidity and the use of similar medications in a nonepileptic population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL CONTROL OF A MOTOR PROGRAM Principal Investigator & Institution: Thomas, James H.; Professor; Genome Sciences; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JAN-1992; Project End 31-JAN-2003 Summary: The goal of the proposed research is to investigate neuron and muscle excitability in the nematode C. elegans. We have identified over 30 genes that regulate excitation of defecation, egg-laying, and body-wall muscles, and we have molecularly cloned five of these genes. The genetics of four of these is strikingly similar: each has dominant gain-of-function mutations (gf) that cause strong defects in muscle excitation, and loss-of-function (lf) mutations cause little or no obvious phenotype. All four genes encode K+ channels. We think that the gf mutations in each K+ channel cause channel activation in vivo, accounting for their strong excitation defects. The fact that lf mutations cause relatively minor defects suggests that the many K+ channels have overlapping functions in vivo. We will continue analysis of these genes and other similar genes identified in genetic screens. The K+ channels will be expressed in cultured cells to study their electrophysiological properties. It will be particularly interesting to study how the gf mutations affect channel properties. Two of these K+ channels are related to the human HERG channel, defects in which cause a cardiac malfunction called long-QT. Long-QT can also be caused by tricyclic antidepressants and certain cardiac anti-arrhythmic drugs. We have evidence that these drugs also block
Studies
35
one (but not the other) of the C. elegans HERG-related channels in vivo and in vitro. We will study the C. elegans channels and their human equivalents to understand the basis for this specificity and its implications for long-QT disorder. We have shown that the fifth muscle excitation gene, called unc- 43, encodes the nematode homologue of calcium-calmodulin dependent protein kinase II (CaMKII). CaMKII is implicated as a key regulator of synaptic activity, particularly of synaptic plasticity that underlies learning and memory. We have many lf mutations in unc-43, including null mutations. These mutants are viable and have complex behavioral abnormalities. There is also one gf mutation in unc-43, and we think that this mutant CaMKII is partially Ca++ independent (activated). This gf mutant is also viable and confers complex defects that are the opposite of those in null mutants. We have begun to use the unc-43 activated mutation to identify extragenic suppressors of its various phenotypes, some of which we expect to encode direct CaMKII substrates. We propose to use a combination of genetic analysis, molecular cloning, and biochemical analysis to characterize these potential targets and to determine whether they are directly phosphorylated by the unc43 CaMKII. We will also continue genetic screens to identify additional potential targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL CONTROL OF GASTROINTESTINAL ACTIVITY Principal Investigator & Institution: Gershon, Michael D.; Professor and Chairman; Anatomy and Cell Biology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-DEC-1977; Project End 31-JUL-2004 Summary: It is likely that the enteric nervous system responds in a paracrine fashion to intraluminal stimulation by release of 5-HT by mucosal EC cells. Intrinsic and extrinsic sensory nerves express 5-HT1P/4 and 5-HT3 receptor respectively. Intestinal epithilial cells express a plasmalemmal 5HT transporter (SERT) similar to that of serotoninergic neurons, which controls the extent to which 5-HT acts as a mucosal signaling molecule. In this proposal mice lacking SERT will be used to 1. determine what compensatory changes occur in the gut of SERT- mice 2. Determine what changes in GI motility and central signaling occur in these mice and 3. Investigate additional intraluminal stimuli that can activate submucosal primary afferent neurons other than pressure distortion in guinea pig, SERT - and control mice. A combination of immunocytochemical, molecular and electrophysiological techniques will be used to address these aims. The SERT - mice model provides a hyperserotonergic model of the gut, which may represent states of disease such as IBS, infection, use of antidepressants etc. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: NEUROBIOLOGY OF DEPRESSION AND ANTIDEPRESSANTS Principal Investigator & Institution: Mann, J John.; Chief; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-MAR-1990; Project End 31-JAN-2008 Summary: (provided by applicant): This competing continuation application proposes a set of patient studies of the serotonergic system in major depression and the effects of somatic antidepressants on the serotonergic system that builds on recent findings from patient studies of the biology of depression and from animal studies of the action of antidepressants. Recently, PET and SPECT studies have begun to provide more direct evidence in both bipolar and unipolar disorders that major depressive episodes are associated with serotonergic system abnormalities. In the current two plus years of funding, we have developed a method for quantifying 5- HT1A binding in human
36
Antidepressants
subjects in vivo using positron emission tomography (PET) and the ligand [11C]WAY100635. We have acquired pilot data indicating lower regional brain 5-HT1A binding in depressed patients. We now propose to systematically investigate the neurobiology of a major depressive episode in both unipolar and bipolar disorders. To determine whether the biological changes associated with depression are reversible, we propose to study the short-term effects of antidepressant treatment, and also to examine a cohort of longterm, remitted and medication-free unipolar patients. In studying the action of antidepressants, we will compare depressed, unipolar patients from the baseline study above, after a six week course of an SSRI, paroxetine. The study of long-term recovered, drug-free patients will help distinguish the effects of recovery from the effects of treatment. The delayed therapeutic benefit of antidepressant medications such as SSRIs has been linked to delayed enhancement of intra-synaptic serotonin levels resulting from 5-HT1A autoreceptor downregulation found in animal studies. SSRIs (or serotonin transporter gene knockout) do not change post-synaptic terminal field 5-HT1A receptors, but downregulate the raphe autoreceptor. These observations have not been adequately tested in man because antidepressant actions on the 5-HT1A receptors may, at least partly, involve the same receptor population that is implicated in the pathogenesis of major depression, such effects need to be evaluated in patients. We propose to test these hypotheses directly in vivo using PET and the ligand [11C]WAY100635, and to quantify the 5- HT1A receptor in healthy volunteers and patients with a major depressive episode. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROTRANSMITTER TRANSPORT Principal Investigator & Institution: Rudnick, Gary W.; Professor; Pharmacology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-MAY-1993; Project End 31-JAN-2004 Summary: (Applicant's Abstract): Biogenic amine transporters are responsible for terminating the synaptic action of serotonin (5-HT), dopamine (DA), and norepinephrine (NE). They are the molecular targets for antidepressants such as imipramine and Prozac as well as for psychostimulants such as cocaine and amphetamines. Efforts currently directed at designing cocaine antagonists make assumptions about the proximity of cocaine and biogenic amine binding sites on the transporter. This application describes experiments designed to map the location of amino acid residues in biogenic amine transporters that are involved with substrate and inhibitor binding. These experiments will provide evidence to test the assumptions now being used to design cocaine treatment medications. Biogenic amine transporters use transmembrane ion gradients to drive neurotransmitter uptake. The coupling stoichiometry for this process is characteristic of each transporter. This proposal outlines plans to determine the ion coupling stoichiometry for DA transport and to compare it with the stoichiometry for NE and 5-HT transport. Mutant transporters will be tested to determine how the stoichiometry of an individual transporter depends on individual amino acids. Taken together, the experiments outlined in this proposal are directed toward the ultimate goal of understanding how each part of the primary sequence of a biogenic amine transport protein participates in the binding and the translocation of substrates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
37
Project Title: OREGON NODE - NATIONAL CLINICAL TRIALS NETWORK Principal Investigator & Institution: Greenlick, Merwyn R.; Public Health and Preventive Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: This proposal calls for the creation of the Oregon Regional Node (OR- Node) of NIDA's national drug treatment clinical trials network on the basis of an Oregon consortium of the researchers, community treatment programs and the state policy group for substance abuse treatment. This consortium, "Oregon Bridging the Gap Between Practice and Research: Forging Partnerships with Community-Based Drug and Alcohol Treatment (Lamb, Greenlick, and McCarty). The proposed OR-Node is a partnership of three research and training organizations, more than 30 collaborating investigators, and the treatment provider community of the State of Oregon. The research group brings resources from the Oregon Health Sciences University, the Kaiser Permanente Center for Health Research, and the Oregon Research Institute. Investigators and operations personnel from these institutions will form the Regional Research and Training Center (RRTC) of OR-Node. Each of these centers of excellence provides senior research personnel to OR-NODE and each brings a special set of other resources to the partnership, such as the approaches and institutional settings, and provides treatment services to all segments of the Oregon population. The structure of the OR-Node operationalizes a full partnership arrangements among the research institutions and the treatment community. Three research concepts are offered in this proposal, selected to exhibit the full-range of research that can be carried out by the ORNode researchers and the type of resources OR-Node offers to the national network. The research concepts are: a quantitative and qualitative assessment of the national network treatment programs developing and testing a model of diffusion of innovation among community-based treatment programs, a clinical trial of antidepressants as an adjuvant in behavioral treatment for drug abuse, and a project top enhance the recruitment and treatment of persons with mild or moderate mental retardation with drug abuse or dependency problems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PATHOPHYSIOLOGY OF ORTHOSTATIC INTOLERANCE Principal Investigator & Institution: Robertson, David H.; Professor of Medicine, Pharmacology And; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Orthostatic intolerance (OI) is the most frequently encountered dysautonomia and the cause of much disability. As many as 500,000 Americans, most of them young women, are affected by it. Yet it is one of the least studied clinical syndromes. There is no established therapy. Its etiology is poorly understood, but is heterogeneous. In this project, we concentrate on identifying mechanisms underlying OI. We developed evidence implicating two mechanisms, a partial dysautonomia referred to as neuropathic postural tachycardia syndrome and a novel genetic disorder due to a functionally significant mutation in the norepinephrine transporter (SLC6A2) which we refer to as norepinephrine transporter (NET) deficiency. This gene is the cocaine- and antidepressant-sensitive "uptake 1" transporter which is crucial for clearing norepinephrine from the synaptic cleft. These two etiologies can explain a range of heretofore inexplicable abnormalities in cardiovascular regulation found in some patients. Our study of NET deficiency patients has led us to unexpected evidence implicating dopaminergic mechanisms in the pathophysiology of the disorder
38
Antidepressants
and perhaps also the orthostatic hypertension of tricyclic antidepressant use. Yet it is clear that a large portion of OI patients have different mechanisms underlying their symptoms. We have found major perturbations in volume regulation and dynamics in a subset of these patients, some of whom have as much as a 26% reduction in plasma volume when they stand for 30 minutes. The sources of interindividual differences in such dynamic volume shifts remain unknown. We propose to elucidate the systemic pathophysiology of human NET deficiency, by assessing autonomic cardiovascular regulation in mouse and human models of NET deficiency and to test specifically tailored pharmacologic interventions to determine if they will correct the pathophysiologic perturbations in OI and in the orthostatic hypeotension of NETblocking antidepressants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOGENETICS OF ANTIDEPRESSANT DRUGS Principal Investigator & Institution: Wong, Ma-Li; Professor; Psychiatry & Biobehav Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This is a revised grant application that describes a meticulous program of patient-oriented research and mentoring. The P.I. is a physicianscientist with an outstanding track record in data based, hypothesis-driven patientoriented and laboratory based investigation, and mentoring. As the Director of the UCLA GCRC Core Lab, Associate Editor of Molecular Psychiatry (Nature Publishing), and as member of the: 1) UCLA Graduate Training Program in Translational Investigation (K30); 2) UCLA Neuroscience Interdepartmental Program; 3) Neuropsychiatric Institute Research Council Group); 4) UCLA GCRC Advisory Board; 5) UCLA Mentored Clinical Pharmacology Research Scholar Program (K12) Advisory Committee the P.I. is uniquely prepared to provide clinical research training and to mentor junior clinical investigators. This award would support the PI's efforts to develop a new mentoring program both in her own area of research and in the core components of clinical research. This includes mentoring in the fundamental skills, methodology, theories, and conceptualizations necessary for the formation of wellrounded, independent, clinical researchers. The P.I. will mentor young investigators in the design of clinical research projects, hypothesis development, clinical pharmacology and pharmacogenomics, scientific writing, and the legal, ethical and regulatory issues related to clinical research. One of the unique aspects of this application is a research and mentoring plan that will address the training of minority clinical researchers and the conduction of research in ethnically identified minority populations. To address these topics, we have developed an outreach effort that consists of a process of community consultation that includes an educational series to understudied ethnic groups. The research proposal tests the hypothesis that genetic polymorphisms might determine a patient's response to antidepressants. This hypothesis will be tested by a prospective clinical phase IIA randomized longitudinal study, using two pharmacological agents (namely Desipramine and Fluoxetine) with demonstrated efficacy in the treatment of depression, in the Mexican-American ethnic population. Clinical status will be assessed with clinical interviews and ratings such as the Hamilton Ratings Scale for Depression, Beck Depression Inventory, and Hamilton Anxiety Rating Scale. These instruments have been extensively validated in Spanish. This is a prospective outpatient treatment study with single- and double-masking, with random assignment of treatment, and with outcomes assessed with clinical measures. All
Studies
39
subjects will undergo a comprehensive intake assessment, and will then have follow-up assessments and treatments according to our protocol. This K-24 award will make possible for the P.I. to significantly increase her time allocation for patient-oriented research and for mentoring of junior trainees and fellows in clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOTHERAPY FOR MINOR DEPRESSION Principal Investigator & Institution: Howland, Robert H.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 17-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): This is a resubmission of a three-site, four-year study to assess the efficacy of St. John's Wort (SJW), standardized to hyperforin content, and citalopram, compared to placebo for the treatment of Minor Depression (MinorD). The proposal differs from the first submission and from ongoing studies of SJW for major depression, in that it: focuses in MinorD only; includes the use of SJW standardized to hyperforin, a more potent formulation; has a refined set of primary and secondary aims; uses a continuous measure of efficacy as the primary outcome of the study; uses random regression models for data analysis; and includes a cross-over phase for non-responders. MinorD has major effects. Patients with MinorD experience substantial morbidity, distress, and dysfunction; even so, less than 10 percent of patients with MinorD receive formal treatment. Many choose to self-medicate with SJW, an untested treatment for MinorD that generates over $200 million a year in sales. We propose to randomize 300 subjects to double-blind flexible doses of SJW up to 1800 mg/day, or citalopram up to 60 mg/day, or placebo, for 12 weeks. At 12 weeks, nonresponders will be crossed-over to active treatment arms previously unassigned; responders will continue to take study medication for another 12 weeks. Stringent criteria will be used to assess improvement in symptoms, dysfunction, and improvement in well-being. The results of this study will have profound public health implications by improving our understanding of the efficacy of SJW and standard antidepressants for the treatment of MinorD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PKC SUBSTRATES & TRANSCRIPTION FACTORS IN MOOD DISORDERS Principal Investigator & Institution: Pandey, Ghanshyam N.; Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-MAR-1998; Project End 31-AUG-2007 Summary: (provided by applicant): Significant progress has been made in the understanding of the neurobiological abnormalities associated with depression and bipolar disorders. However, the specific sites of such abnormalities in these disorders are still unclear. Several studies indicate increased 5HT2A receptors and 5HT2A receptor linked phosphoinositide (PI) signaling activity in the brain and platelets of patients with mood disorder. The studies in the previous funding period, indicated that 5HT2A receptors and IP3 receptors are increased in the platelets of unipolar patients, PKC activity, PLC activity and selective isozymes of PKC and PLC are decreased and MARCKS, a substrate for PKC increased in the platelets of bipolar patients. In the proposed research, the main objective is to extend our findings and to study further downstream events in the PI signaling system, such as: PKC substrates and transcription factors in the platelets and neutrophils obtained in drug-free unipolar and bipolar
40
Antidepressants
patients. More specifically, we will study PKC, MARKCS and GAP43 the substrates for PKC, in the platelets of unipolar and bipolar patients, DNA binding activity of transcription factors AP-1, GRE, DNA binding activity, protein expression and mRNA levels of another transcription factor CREB in the neutrophils of unipolar and bipolar patients. In addition, we will study the activity, protein level and mRNA levels of GSK3B and protein levels of B-catenin, the two important components of the WNT pathway that appears to be related to and may be regulated by PKC and has been implicated to be abnormal in bipolar disorders. Our proposed studies are based on our central hypothesis that an abnormal PT signaling system in patients with mood disorders is associated with abnormality of several of its components leading to abnormality of transcription factors and gene expression.These studies will enhance our understanding of the involvement of transcription factors and PKC substrates in the pathophysiology of unipolar and bipolar disorders and may indicate if they may be possible sites for therapeutic action of antidepressants and mood stabilizing drugs, thus, may result in more appropriate and better treatment these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREDICTION OF OUTCOME DURING FLUOXETINE Principal Investigator & Institution: Mc Grath, Patrick J.; Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2003 Summary: About half of the patients who respond to antidepressants improve as a result of the natural course of the illness or due to nonspecific or "placebo" effects rather than pharmacologic effects. Since current practice dictates drug maintenance for all responders to antidepressants, much continuation/maintenance pharmacotherapy may be unnecessary. If "placebo" responses to an active drug could be identified, unnecessary medication could be discontinued, decreasing morbidity and cost. Knowing that initial improvement is attributable to a "placebo" effect would also permit more rational treatment of relapses during continuation treatment. Multiple studies have shown that the analysis of patterns of response to acute antidepressant treatment differentiate "true" or pharmacologic responses from "placebo" or nonspecific responses. Preliminary data presented in this proposal suggest that pattern analysis also distinguishes patients who require medication during continuation/maintenance from those who do not. In this study, the predictive value of acute response pattern will be tested prospectively using a placebo-controlled discontinuation design. Success in this would allow clinically useful recommendations for continuation treatment to be made based on the collection of relatively simple and easily acquired clinical data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PREDICTION CONTINUATION
OF
OUTCOME
DURING
FLUOXETINE
Principal Investigator & Institution: Fava, Maurizio; Director, Depression Clinical & Res. Pro; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2002 Summary: About half of the patients who respond to antidepressants improve as a result of the natural course of the illness or due to nonspecific or "placebo" effects rather than pharmacologic effects. Since current practice dictates drug maintenance for all responders to antidepressants, much continuation pharmacotherapy may be unnecessary. If "placebo" responses to an active drug could be identified, unnecessary
Studies
41
medication could be discontinued, decreasing morbidity and cost knowing that initial improvement is attributable to a "placebo" effect would also permit more rational treatment of relapses during continuation treatment. Multiple studies have shown that the analysis of patterns of response to acute antidepressant treatment differentiate "true" or pharmacologic responses from "placebo' or nonspecific responses. Preliminary data presented in this proposal suggest that pattern analysis also distinguishes patients who require medication during continuation from those who do not. In this study, the predictive value of the acute response pattern will be tested prospectively using a placebo-controlled discontinuation design. Success in this would allow clinically useful recommendations for continuation treatment to be made based on the collection of relatively simple and easily acquired clinical data. The present study involves the enrollment of 700 patients with major depression at two sites. Responders to a 12-week acute trial of fluoxetine will be prospectively randomized for 24 weeks of double-blind continuation treatment based on their pattern of response ("placebo" or "true drugs type). In each group, 50% of the patients will be assigned to remain on fluoxetine and 50% will switch to placebo. Differences in relapse rates will be examined in the four groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTING DEPRESSION RECURRENCE IN DIABETES Principal Investigator & Institution: Lustman, Patrick J.; Professor of Psychiatry; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-JUL-2003 Summary: Major depression in diabetes is a prevalent condition associated with an increased risk of diabetes complications. The investigators recently proved that shortterm treatment of depression with antidepressants in diabetes is effective. Medication was not continued beyond the point of depression remission and, unfortunately, depression recurred in approximately 60 percent of patients within 1st year. Only eight percent remained euthymic over a 5-year follow-up period. Depression in diabetes has also been associated in cross- sectional studies with poor glycemic control, presumably an important intermediate in its association with complications. It is not known whether maintenance depression-treatment strategies increasingly employed in medically well subjects would be effective in diabetes, either to reduce depression recurrences or influence the long-term course of glycemic control. The investigators propose a longitudinal, two-site, two-phase (participation <18 months), controlled treatment outcome study in patients with non insulin dependent diabetes mellitus (NIDDM): 1) to determine if emerging practices for preventing depression recurrences in nondiabetic subjects should be applied to this medically ill group, and 2) to prospectively determine the inter-relationship of depression and glycemic control. In the open-label phase of the study, 262 depressed NIDDM patients will be treated with sertraline; 156 of these patients are expected to achieve recovery from depression and be assigned randomly to continued pharmacotherapy (n=78) or to placebo (n =78) and followed for a period up to 14 months. Survival methods will be used to determine the efficacy of maintenance pharmacotherapy; a comprehensive set of outcome measures will be used to determine the benefits of remaining depression-free in terms of compliance with diabetes treatment, social and occupational functioning, global well- being, and quality of life. Repeated measures ANCOVA and longitudinal modeling of mood and glycemia will be used to determine the benefits of maintenance sertraline and euthymia on glycemic control. The investigators hypothesize: 1) that maintenance pharmacotherapy for depression in diabetes will produce superior results on multiple depression and
42
Antidepressants
psychosocial outcome measures; 2) that depression and glycemic control covary in longitudinal follow-up; and 3) that maintenance antidepressant therapy will produce durable improvements in glycemic control and attenuate depression symptoms in response to hyperglycemia. In short, they expect that maintenance antidepressant treatment in diabetes will prevent or delay depression recurrence, promote durable improvements in glycemic control, and interrupt the vicious cycling of depression and glucose dysregulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF DEPRESSION IN LOW-INCOME SINGLE MOTHERS Principal Investigator & Institution: Peden, Ann R.; Associate Professor; None; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: The ultimate goal of this program of research is to decrease the incidence of clinical depression in high risk individuals through prevention intervention. Lowincome, single mothers are at high risk for depression which may have negative effects on their children. The specific aim of this randomized controlled prevention trial is to test the effects of a cognitive-behavioral intervention designed to reduce negative thoughts, chronic stress, and depressive symptoms and increase self-esteem of low income single mothers experiencing subclinical depressive symptoms. In addition, the effects of the intervention on mothers' reports of behavioral problems of their 2- to 6year old children will be tested. While cognitive-behavioral interventions with depressed individuals have been used extensively, the effects of affirmations and thought stopping techniques in reducing the risk of depression have not been tested empirically. A sample of 550 single mothers at least 18 years of age will be recruited for the cross-sectional phase of this study. Inclusion and exclusion criteria are: (1) no prior treatment for psychiatric care; (2) not now or ever on antidepressants; (3) never diagnosed with clinical depression; (4) not suicidal; (5) never married, separated at least 6 months, or divorced; (6) at least one child 2 to 6 years of age living with the mother; (7) no child under the age of 2; (8) not pregnant by self-report; (9) not currently in counseling; (10) at or below 185% of Federal poverty level guidelines by family size. Baseline data on depressive symptoms, negative thoughts, self-esteem, chronic stressors, and mothers' report of child behavior will be collected from all women. Recruitment will continue until 160 women with a Beck Depression Inventory score between 9 and 35 and/or a Center for Epidemiologic Studies--Depression Scale score between 16 and 40 are identified and agree to participate in the clinical trial. As women are recruited for the intervention phase, each will be randomly assigned to the control or experimental condition. The intervention consists of six one-hour per week group sessions that target identification and management of negative thinking as it effects depressive symptoms. Though stopping and the use of affirmations (positive self-talk) are the primary techniques that are taught. Experimental and control subjects will be re-interviewed at one-month, six-months and twelve-month post-intervention to assess their negative thinking, depressive symptoms, self-esteem, and chronic stressors and to obtain reports of their children's behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
43
Project Title: PREVENTION OF POST-STROKE DEPRESSION-TREATMENT STRATEGY Principal Investigator & Institution: Robinson, Robert G.; Professor and Head; Psychiatry; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Previous studies have shown that about 35% of all depression occurring in the 2 years following stroke begin after the acute in-hospital period. We have shown that both acute and delayed onset depression influence cognitive and ADL recovery throughout the 1st year following stroke. A recent treatment study aimed at preventing the development of post-stroke depression found that nortriptyline (NT) and fluoxetine were effective in preventive depression (i.e., 1 of 13 patients given NT and 1 of 13 given fluoxetine became depressed compared with 5 of 15 patients given placebo; p=.03). During the next 6 mos. after treatment, a significantly greater number of active treatment patients developed depression compared with patients given fluoxetine or placebo. This increased rate of depression among the treated patients raises the question of whether a longer period of treatment would continue to prevent depression. Furthermore, a 7-year follow-up of the 37 non-depressed patients who were given fluoxetine, nortriptyline or placebo found that those given antidepressants were more likely to survive than those given placebo (Kaplan Meier Log Rank, x(2)=4.3, df=1, p=0.4)(i.e., 65% treated survived vs 29% of placebo). This grant will examine these questions by treating consenting non-depressed stroke patients who are within the first 3 mos. post-stroke. Patients will be given problem-solving therapy (PST) over 12 mos. or 12 mos. of double blind treatment with NT, citalopram or placebo. Patients who develop depressing meeting criterion for major or minor depression of at least 2 weeks duration will be given all of the tests intended to be given at 12 mos. and then will be terminated so that their depression can be treated. After 1 year of treatment, all patients will be followed without treatment of another 6 mos. We will determine whether psychosocial or pharmacological treatment provides extended protection from depression and thereby enhances post-stroke recovery. We will also determine whether abnormalities in startle response either before or after treatment or atrophy of specific rain regions are correlated with the development of depression. The significance of this study is that it will answer the most important question with remains in the therapeutics of post-stroke depression and that is whether prophylactic antidepressant treatment of this population should be given to all stroke patients because it will enhance their recovery from stroke by decreasing their likelihood of suffering the emotional, physical, cognitive and mortality consequences of depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PRIMARY CARE DIAGNOSIS & TREATMENT OF DEPRESSED CHILDREN Principal Investigator & Institution: Rushton, Jerry L.; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2003 Summary: (provided by applicant): Dr. Rushton proposes a career award to study and improve the diagnosis and treatment of children and adolescents with depressive disorders by primary care physicians. Recent changes in health care have important implications for management of depression including primary care gatekeeping, limited access to mental health providers and counseling, and new antidepressants. Yet, little
44
Antidepressants
information exists on the current role of primary care physicians, or how these physicians can improve coordination of care and services to improve patient outcomes. Dr. Rushton plans two phases of research to address his aims using complementary methods: (1) analysis of health system administrative data, (2) survey of primary care physicians. The proposed studies will describe depressed children and adolescents and their health care utilization; define the scope of primary care and relationships to mental health providers; analyze variations in prescriptions, referrals, and management of depressed youth; and examine influences on physician triage and treatment decisions. This research will be accomplished over five years and incorporate coursework and training in survey techniques (quantitative and qualitative), statistical analysis, pharmacology, child and adolescent psychiatry, and health services research. In the final years of the grant period, Dr. Rushton will develop a grant proposal based on his findings to design interventions to improve the quality of mental health services and integrate primary care with specialty and community providers. The University of Michigan provides the clinical and research environment to accomplish the proposed aims and career goals with support from many disciplines led by co-mentors, Dr. Gary Freed (Pediatric Health Services Research) and Dr. John Greden (Psychiatry). The candidate will acquire skills and connections that will allow him to become an independent researcher working at the important interface of delivery systems. The proposed research will set the stage for additional mental health services for children, quality improvement interventions on prescriber practices, and health system efforts to coordinate mental health services with primary care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION
PROBLEM-SOLVING
TREATMENT
FOR
PRIMARY
CARE
Principal Investigator & Institution: Oxman, Thomas E.; Professor; Psychiatry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Minor depression is one of the most common types of depressive disorders in primary care. It is not clear that antidepressants are indicated for minor depression, and even if they are, a substantial proportion of patients cannot or will not take them. Alternative treatment approaches are indicated. The purpose of this project is to use a four-week watchful waiting period to identify patients with persistent minor depression, potentially most in need of depression specific treatment, and then test the therapeutic effect of Problem- Solving Treatment for Primary Care (PST-PC), a manual driven, six-session, behavioral treatment for depression in primary care. In this project, 300 primary care, minor depression patients will be identified and followed. The relationship of patient predictors to remission will be examined. After four weeks, patients who do not demonstrate symptomatic remission (approximately 50 percent or 150 patients) will be entered into a randomized nine-week clinical trial comparing PSTPC with Usual Care. Subjects will be followed for six months after completing the trial. The primary aim of this project is to test the therapeutic effect of PST-PC versus Usual Care for persistent minor depression in primary care. As a subsidiary aim the project will examine the relationship of characteristics of the patient (social support, adverse life events, personality traits, comorbidity) to early remission of minor depression. Patient and therapy characteristics will also be examined as predictors of recovery six months after the trial. The broader, long-term goal of this line of investigation is to disseminate practical, non-pharmacologic mental health treatments for use by non-physician
Studies
45
practitioners (e.g. psychologists, nurses, social workers, counselors) who will increasingly be working in primary care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROPOSED ACETYLTRANSFERASE
ROLE
FOR
NEURONAL
SEROTONIN
N-
Principal Investigator & Institution: Manev, Hari; Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 10-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant) N-acetylserotonrn (NAS) is synthesized from serotonin by an action of serotonin N-acetyltransferase (AANAT). Although evidence of hippocampal and cerebellar localization/synthesis of NAS was provided several years ago, it is still believed that in mammals, AANAT is almost exclusively expressed in the pmeal gland and in the retina, and that its neuronal localization is restricted to the lower organisms, such as the fruit fly. We recently reported that AANAT mRNA is expressed in the rat hippocampus and that it is up-regulated by the antidepressant fluoxetine (administered chronically); others found that NAS possesses antidepressant-like activity in a rodent behavioral despair test. Furthermore, we a) identified those neurons in the rat CNS that express AANAT mRNA, including cerebellar granule neurons (CON), b) established primary CON cultures in which AANAT mRNA is normally expressed and is up-regulated by isoproterenol, c) demonstrated that CON cultures treated with 3Hlabeled serotonin synthesize NAS, and d) found that in these neurons NAS may act as a functional inhibitor of nitric oxide (NO) synthesis. We hypothesize that NAS can affect neuronal functioning via the inhibition of NO synthase (NOS) activity and/or expression (possibly by an action on the synthesis of the NOS cofactor tetrahydrobiopterin BH4), and that neuronal expression of AANAT could be a target for the action of antidepressant treatments. These hypotheses will be tested in the following 6 AIMs: (1) Characterize in primary rat CON cultures andin BV-2 microglial cultures the pathways involved in NAS-triggered inhibition of NOS, including the synthesis of tetrahydrobiopterin, BH4; (2) Characterize in vitro the role of AANAT in metabolizing serotonin into NAS and in the synthesis of BH4 and/or NOS using cultures from AANAT mutated mice (expressing enzymatically inactive AANAT) and normal mice; (3) Characterize in AANAT-mutated and normal mice the basal and the stimulated BH4 and NO synthesis; (4) Characterize in rat CON cultures the neurotransmitter systems capable of regulating AANAT expression; (5) Investigate in rats whether antidepressants other than fluoxetine increase the brain content of AANAT mRNA, and whether all brain regions expressing AANAT and the pineal glands are equally affected; (6) Characterize whether the AANAT-mutated mice respond to antidepressant differently from normal mice in a model of forced swimming. Techniques to be used include: quantitative reverse transcription/polymerase chain reaction (RT-PCR) and in situ RT-PCR for AANAT mRNA; assays of NOS activity, nitrite and BH4 contents; and the forced swimming test. We expect the results to elucidate the role of AANAT/NAS in neuronal functioning, and in the long term, in the pathobiology of depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PSYCHOSTIMULANT TRANSPORTERS
RECOGNITION
BY
SEROTONIN
Principal Investigator & Institution: Barker, Eric L.; Assistant Professor; Medicinal Chem/Molecular Pharm; Purdue University West Lafayette West Lafayette, in 479072040
46
Antidepressants
Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: The serotonin transporter (SERT) is the molecular target for most antidepressant drugs as well as many drugs of abuse. Antidepressants such as paroxetine, fluoxetine, and imipramine bind to the transporter and inhibit serotonin uptake, thereby prolonging the extracellular lifespan of the neurotransmitter. The abused psychostimulants cocaine and amphetamine also bind to the transporter, but have distinct pharmacologic effects leading to abuse potential and possible neurotoxicity. Despite the cloning of SERT in the early 1990's, very little information is available regarding the molecular and cellular neurobiology surrounding the function of this transport protein. This project uses a multidisciplinary approach aimed at significantly advancing knowledge regarding the molecular pharmacology of psychostimulants at SERTs. The studies will use multiple techniques including expression and characterization of recombinant transporters in mammalian cells, electrophysiology, immunoblotting, the formation of chimeric proteins, and sitedirected mutagenesis to identify amino acids involved with specific transporter functions including antagonist and substrate binding. In addition, computer-assisted structure-activity studies of cocaine and amphetamine derivatives will be coupled with mutagenesis in an attempt to identify direct ligand- transporter interactions. Therefore, the specific aims of this project are 1) to identify transporter domains and residues involved in recognition of SERT antagonists such as cocaine and 2) to determine the contributions of specific SERT domains to substrate properties such as translocation, efflux, and channel- like activity. The proposed strategies will provide critical new information linking protein structure to functional properties of the transporter and an enhanced understanding of the molecular mechanisms of action for psychotherapeutic and abused drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PUFA AUGMENTATION IN TREATMENT OF MAJOR DEPRESSION Principal Investigator & Institution: Gertsik, Lev G.; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAR-2005 Summary: (provided by applicant): This is a second revision of an Investigator-Initiated Exploratory/Developmental Research (R21) grant application to the National Center for Complementary and Alternative Medicine to explore the use of polyunsaturated fatty acids (PUFAs) as an augmentation strategy for the treatment of unipolar major depression. Major depression is a common mental disorder, and is associated with serious functional impairment, morbidity and mortality. Moreover, it also produces a significant financial burden on our society. Despite the availability of numerous pharmacologic and psychotherapeutic interventions, the current treatment of depression is not optimal. Even in patients who do respond to treatment, remission is rarely complete. In addition, the onset of action of antidepressants is delayed; the drugs usually must be taken for three weeks or more before improvement is clinically discernible. Accordingly, a number of augmentation strategies to hasten the onset of activity and increase the efficacy of traditional antidepressants have been proposed and tested, but many of these produce significant side-effects, and some patients still do not respond. PUFAs are found in high concentrations in the central nervous system, and they appear to be involved in many aspects of signal transduction. Recently, evidence has surfaced suggesting that the dietary intake of PUFAs might be related to depression, and the administration of PUFAs might reduce depressive symptomatology. In this application, we propose testing the hypothesis that administration of one of the PUFAs,
Studies
47
eicosapentanoic acid (EPA), in combination with a selective serotonin reuptake inhibitor (SSRI) antidepressant will improve treatment outcome in unipolar major depression. In addition, we will determine whether the onset of antidepressant activity occurs more rapidly when EPA supplementation is combined with selective serotonin uptake inhibitor. The results of the proposed study might provide a new, economical, safe, and potentially important alternative approach to the treatment of unipolar major depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REAL-TIME NOREPINEPHRINE TRANSPORTER KINETICS Principal Investigator & Institution: Schwartz, Joel W.; Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 13-MAR-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Central nervous system noradrenergic signaling modulates attention, mood, arousal, learning and memory. Specifically, norepinephrine reuptake is implicated in the pathology of major depression, posttraumatic stress disorder and attention deficit disorder. Therapeutic agents for the treatment of depression inhibit norepinephrine transporter (NET) and serotonin transporter (SERT) activities, elevating the concentration of these transmitters in the synaptic cleft. Antidepressants that inhibit NET, such as desipramine, are effective for the treatment of depression. Biogenic amine transporters are also biological targets for drugs of abuse, such as cocaine and amphetamine. The work described in this research proposal investigates substrate translocation, in which we develop novel methodology for measuring NET, SERT and dopamine transporter (DAT) activity. The fluorescent-based uptake assay described in Specific Aim I can be used as a nonisotopic method for highthroughput drug screening probing for compounds that interact with NET, SERT or DAT. The studies outlined in Specific Aim II examine the correlation between substrate and charge movement. Information garnered from these studies, can help assess the contribution of neurotransmitter transporters to synaptic transmission. The advancement in methodology enables the analysis NET activity in individual neurons, thus providing insight into endogenous NET function. These data may also provide a better understanding of therapeutic agents and drugs of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: RISK FACTORS FOR BREAST CANCER IN ORANGE COUNTY, FLORIDA Principal Investigator & Institution: Samet, Jonathan M.; Chair and Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant)Previous epidemiologic and experimental evidence suggesting a possible association between antidepressant drugs and the risk of breast cancer have several methodological weaknesses. The broad objective of this study is to investigate this association while addressing the flaws in previous studies. The primary hypothesis is that antidepressants increase the risk of breast cancer. This is a population-based case-control study. The 55-74 year-old cases to be selected from the Florida State Cancer Registry will be 400 breast cancer cases (ICD-9 code 174), diagnosed between 1/1/97 and 12/31/00, or the latest month in 2001 for which data are complete. The controls will be 400 female Orange County residents, and will be selected from Florida State Drivers' License files. They will be frequency-matched with cases on race
48
Antidepressants
and age (5-year intervals). Telephone interviews will be conducted by trained interviewers to collect data on past use of antidepressants, depression history and many potential confounders, using a Structured Questionnaire and the Diagnostic Interview Schedule (DIS). The data will be analyzed by means of unconditional logistic regression analysis. Odds ratios (ORs) and 95% CIs will be reported for breast cancer risk associated with antidepressant use, and will be adjusted for age, race, family history of breast cancer, alcohol, and other potential confounders. Additional analyses will include analysis stratified by depression status, dose-response analysis, and analysis for interactions between antidepressants and each of: depression, family history of breast cancer, history of benign breast disease and reproductive history. The results will be discussed in terms of implications for future use of antidepressants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF CREB IN NUCLEUS ACCUMBENS IN MOOD AND MOTIVATION Principal Investigator & Institution: Nestler, Eric J.; Chairman; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Project 1 focuses on the ability of the transcription factor CREB in the nucleus accumbens (NAc) to regulate mood and motivational state. We have considerable evidence that increased CREB function in this brain region, which occurs under several conditions of stress, causes a decrease in an animal's sensitivity to emotional stimuli, regardless of whether the stimuli are aversive or rewarding. Reduced CREB function has the opposite effect. These findings suggest that CREB in the NAc may function as a key molecular gate between emotional stimuli and their behavioral responses. A possible relationship between this phenotype and symptoms of anhedonia and reduced motivation in depressed humans will be explored in further studies of animal models, including analysis of various stress models, sexual behavior, intracranial self-stimulation, and social interactions. Viral-mediated gene transfer and inducible, cell-targeted mutations in mice will be used in these experiments. Another goal of the proposed studies is to investigate the cellular specificity of stress regulation of CREB in the NAc, and its possible modification by antidepressant treatments. Related studies will explore the molecular mechanisms by which stress and antidepressants regulate CREB in this brain region. A third goal of the proposed studies is to identify target genes through which CREB produces these effects on mood and motivation. The genes encoding the opioid peptide dynorphin and the AMPA glutamate receptor subunit GluR1 are two such targets of CREB that will be examined in this Project. Additional targets will be identified with DNA microarrays. Among the targets identified in initial array experiments are BDNF and NPAS2, the major gene products of interest in Projects 2 and 4, respectively. As stated earlier, CREB function is a major theme in this Center. All of the subsequent Projects of this Grant represent extensions of our central hypothesis that CREB in the NAc is a key regulator of hedonic or affective state. Subsequent Projects extend this theme by examining other molecular constituents of NAc neurons, which are regulated by CREB and help control CREB activity, for their role in this complex behavioral, phenotype. In addition, the other Projects explore a related role for CREB in certain hypothalamic (Project 3) and VTA(ventral tegmental area) (Project 2) neurons, which, along with the NAc, form a neural circuit controlling appetitive behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
49
Project Title: RUPP-PI Principal Investigator & Institution: Brent, David A.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant) : This U10 proposal, RUPP-PI in Pittsburgh is to establish an NIMH Research Unit for Pediatric Psychopharmacology-Psychosocial Intervention in Pittsburgh. The proposed unit builds on the strengths of the Pittsburgh site in clinical epidemiology of mood disorders and suicidal behavior, psychosocial treatment development, pharmacokinetics of SSRI's, and participation in numerous success- fully performed, single and multi-site clinical trials involving CBT, antidepressants, and their combination for mood and anxiety disorders. Resources to support this program of research and training include a T32 postdoctoral training grant in child psychiatry research, an Intervention Research Center on early-onset mood and anxiety disorders, a RUPP devoted to pharmacokinetics of antidepressants, and a statesupported specialty clinic for mood disorders and suicidal behavior. The exemplar research protocol, "Treatment of Adolescent Suicide Attempters" (TASA), targets a major public health issue: although adolescents in this country suffer 2 million suicide attempts annually, no large scale, multimodal controlled intervention studies for this condition have been conducted. The proposed 5-year study will determine the effectiveness of a multi-modal treatment intervention to prevent further reattempts in 480 depressed adolescents attempters, ages 12 to 18, at 8 sites. The Experimental Treatment Group will receive a 24-week course of antidepressant medication management (MM), and cognitive behavioral therapy. The Control Treatment Group will be referred to a community provider for standard clinical care plus enhanced clinical monitoring and case management to encourage treatment adherence. Both groups will be assessed at baseline 2, 4, 8, 12, 24, 36 and 48 weeks by an independent evaluator blind to treatment assignment. We hypothesize that the experimental treatment will result in fewer suicide attempts, diminished depression and severity of suicidal ideation, and greater global improvement scores differ between the 2 groups over a one-year period of observation. The expertise and experience at this RUPP-PI site also will be directed to train new investigators. In creating TASA, a collaborative group of 8 applicants forged the ability to work together. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SAM-E TREATMENT OF DEPRESSION IN PARKINSON'S DISEASE Principal Investigator & Institution: Dirocco, Alessandro; Beth Israel Medical Ctr (New York) 1St Ave at 16Th St New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-MAY-2005 Summary: (provided by applicant): S-Adenosyl-methionme (SAM-e) is a molecule present in all eukaryotic cells, where it serves as the methyl-group donor for a number of metabolic functions. In the nervous system, SAM-E is essential in the metabolism of cathecholamines and may play an essential role in receptor stabilization and myelin formation and repair. SAM-a is available in the USA as a food supplement and is promoted as a mood enhancer. Parkinson's disease (PD) is commonly associated with depression, but conventional antidepressants have limited efficacy in parkinsonian patients and may exacerbate motor symptoms. SAM-a improves dopamine transmission, may have a beneficial effect on dopamine receptors and may be a good alternative to the currently used antidepressants. We have conducted a ten-week pilot study of SAM-e in thirteen depressed patients with PD. All patients had been previously
50
Antidepressants
treated with other anti-depressant agents and had no significant benefit or had intolerable side effects. Eleven patients completed the study, and ten had at least a 50% improvement of the 17point Hamilton Depression Scale (HAMD), while one patient did not improve. The mean HAMD score before SAM-e treatment was 27.09 greater than or equal to 6.04 SD), and was 9.55 +/-7.29 SD) after treatment (p<0.0001). Although uncontrolled and preliminary, the study suggests that SAM-e is well tolerated and may be a safe and effective alternative to other antidepressants used in PD. Therefore, we propose a controlled, double-blind study to investigate whether SAM-a is safe and effective in the treatment of depression associated with Parkinson's disease. The efficacy of SAM-e will be compared to placebo and to Citalopram, a Selective Serotonin Reuptake Inhibitor commonly used for the treatment of depression in PD. Secondary aims include investigating: a) the effect of SAM-e on the motor symptoms of PD; the effect of SAM-e on the serum concentrations of metabolites of the trans-methylation pathway; b) whether the clinical effect of SAM-e is associated with the presence of common genetic polymorphisms encoding enzymes of the trans-methylation pathway; and d) whether SAM-e treatment is associated with improvement in neuropsychological functioning. The submission of this application was previously discussed with officers of the National Center for Complementary and Alternative Medicine (NCCAM), who found the clinical and scientific scopes of this application compatible with the mission of their Institute, and recommended the submission of this grant proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEROTONERGIC ANTIDEPRESSANT IN PARKINSON'S DISEASE Principal Investigator & Institution: Richard, Irene H.; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Depression is common in patients with Parkinson?s disease (PD) and is a major factor negatively impacting quality of life. To date, there have been no well-designed clinical trials of antidepressant pharmacotherapy for depression in PD. Although selective serotonin reuptake inhibitor (SSRI) antidepressants are often viewed as first-line treatment for depression, their efficacy and tolerability in PD have not been established. In particular, concerns have been raised that they might worsen Parkinsonian motor function. Proposed is a series of activities to develop the elements essential to conduct a randomized, double blind, placebo-controlled, parallel groups trial of the SSRI paroxetine for patients with PD and depression. During the one-year planning grant, collaborative arrangements will be solidified and adequate plans for subject recruitment will be made. Case report forms and a complete manual of study operations and procedures will be developed. At the end of the planning grant, everything will be in place for the clinical trial itself. The clinical trial has been designed to determine the efficacy of paroxetine in reducing depressive symptoms. Information regarding the effects of paroxetine on quality of life, motor function, cognition and its general tolerability will also be obtained. One hundred twenty subjects will be enrolled among 6 centers and each subject will participate in the trial for 12 weeks. The planning grant will set the stage for the clinical trial that will clarify many important questions regarding the optimal pharmacotherapy of depression in patients with PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
51
Project Title: SHORT-TERM VS LONG-TERM TREATMENT FOR SERVERE PMS Principal Investigator & Institution: Freeman, Ellen W.; Research Professor; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-FEB-1985; Project End 31-JAN-2007 Summary: (provided by applicant): Severe premenstrual syndrome (PMS) is a chronic and complex mood disorder that involves a constellation of mood, behavioral and physical symptoms linked to the menstrual cycle with sufficient severity to disrupt functioning for as much as several weeks each menstrual cycle. Five to ten percent of reproductive-age women meet strict diagnostic criteria, but up to 40 percent seek medical treatment for this disorder. The efficacy of serotonin reuptake inhibiting antidepressants (SKIs) is clearly demonstrated for severe forms of PMS in short-term treatment trials. However, there are no long-term studies of severe PMS, and it is not known how long medication should be continued following symptom relief, to what extent and how rapidly symptoms return after stopping medication, or whether there is any additional improvement with long-term treatment. The proposed study compares short-term treatment (4 months) and long-term treatment (12 months) of severe PMS with the SRI sertraline and double-blind switch to placebo to study the effects of discontinuing medication. The aims are as follows: 1) Compare between short- and long-term treatment the percent of subjects relapsed within 6 months after discontinuing medication; 2) Determine the time to relapse after discontinuing medication and compare the time between the short- and long-term treatment groups; 3) Compare symptom levels while on drug between the short- and long-term treatment groups; 4) Compare the trend over time in symptom scores during the placebo period between the short- and long-term treatment groups. It is important to systematically examine these questions in order to minimize the risks and costs of medication if it is not needed or to support using medication if it is needed to prevent relapse and its attendant distress and disruptions of daily functioning for the large numbers of women who suffer from the disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SSRI RX: EFFECTS ON SELF EFFICACY AND MATERNAL ROLE Principal Investigator & Institution: Wisner, Katherine L.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 15-AUG-1999; Project End 31-JUL-2005 Summary: (provided by applicant): Thirteen percent of women experience depression during the first 12 months postpartum, which adversely impacts key aspects of maternal role functioning, i.e. maternal-infant interaction, infant caretaking, gratification in the maternal role, and use of preventive health services for the infant (immunizations and well-child visits). Antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs) improve depression symptoms and social functioning, but their impact upon maternal role functioning has not been determined. The purpose of this naturalistic, longitudinal supplement is to investigate the impact of SSRI treatment on maternal role functioning in women during the first postpartum year. In addition, we will determine if self-efficacy is higher in depressed women who are treated with SSRIs, and we will test if a model of self-efficacy, depression, SSRI use, and social support predicts maternal role functioning. The sample (N=270) will consist of 3 groups of postpartum women (depressed, treated with SSRIs; depressed and not treated; not depressed, not treated) who are evaluated 4 times. The study is a supplement to an NIMH funded investigation, Antidepressant Use During Pregnancy (5 R01 MH60335-02, Katherine L.
52
Antidepressants
Wisner, M.D. PI), which addresses the effects of both depression and drug intervention during pregnancy and the postpartum period on mothers and infants. In this study, data on many aspects of the psychosocial environment of pregnant and parenting women are collected in order to isolate developmental and other effects of prenatal drug exposure on the infant. Using much of the same data, the supplement enhances and extends research currently funded by NIMH to Dr. Wisner by asking an additional question that is a national health priority: Does treatment of PPD with antidepressants improve a woman's ability to fulfill key aspects of functioning in the maternal role? Results of the study will inform women and their health care providers on outcomes of the use of SSRIs in depressed, postpartum women, assisting with decision-making on the treatment of postpartum depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRESS REGULATION OF 5HT RECEPTORS AND THE HPA AXIS Principal Investigator & Institution: Lopez, Juan F.; Associate Professor; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant) The goal of this proposal is to study the regulation and interaction of specific molecules of the Serotonrn (5HT) system and the LimbicHypothalamic-Pituitary-Adrenal (LHPA) axis in key regions of the rat brain (hippocampus, hypothalamus, and prefrontal cortex); using biochemical and neuroanatomical tools. Dysfunction of the 5HT system and overactivity of the LHPA axis are two of the most replicated biological fmdings in depression. Our overall hypothesis is that the alterations in these two systems are closely linked. Specifically, based on our previous animal and human postmortem studies, we propose the following hypotheses: 1) that glucocorticoids play a central role in the 5HT and corticosteroid receptor dysregulation found in depression and in chronic stress; 2) that failure of an antidepressant to prevent the LHPA overactivity is associated with a failure to reverse these receptor changes; 3) that blocking the effect of glucocorticoids in brain will prevent the receptor abnormalities; and 4) that environmental factors early in life can contribute to LHPA 'dysfunction' and 5HT receptor abnormalities. To answer these hypotheses, on Aims 1 and 2 we will use rats to investigate whether chronic stress causes concomitant changes in brain 5HT, corticosteroid, and CRH receptors. We will also investigate whether antidepressants prevent these changes, and whether circulating corticosteroids have a central role on these stress-induced receptor 'abnormalities'. Aim 3 will investigate whether administration of DHEA, an androgen with antiglucocorticoid properties, or administration of a CR11 receptor antagonist, will reverse and/or prevent these receptor changes. Aim 4 will investigate whether maternal deprivation in rats makes the brain more vulnerable to these receptor changes in adulthood.We will use in situ hybridization, radioimmunocytochemistry, and receptor autoradiography to quantify: 5HT1a and 5HT2a receptors, 5HT transporter, Glucocorticoid and Mineralocorticoid receptors, Corticotropin releasing hormone (CRH), CRH receptors, and CRH binding protein. This proposal brings together molecular/neuroanatomical tools, to increase our knowledge of the link between stress and depression. It is hoped that these series of 'preclinical' animal studies will help increase our understanding of the pathophysiological consequences of chronic stress, will help clarify the role of elevated corticosteroids in depression, and will give us someclues about how to treat, or prevent, the cumulative effect of hypercortisolemia in brain.
Studies
53
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL/TROPHIC HYPOTHESIS FOR ANTIDEPRESSANT ACTIONS Principal Investigator & Institution: Koliatsos, Vassilis E.; Professor; Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Mechanisms of antidepressant drug actions are not clearly understood. In the present application, we propose that antidepressant drugs work via a classical trophic mechanism, i.e. proliferation of terminal branches (sprouting) of central monoamine axons in cortex and the limbic system. We also propose that the molecular signals mediating these structural effects are neurotrophins, e.g. for the serotonin system, the critical signal is brain-derived neurotrophic factor (BDNF). Our experimental design takes a stepwise approach using cellular and molecular methodologies, including transgenic mice. We first evaluate the ability of serotonin (5-HT)- and norepinephrine (NE)-promoting compounds to cause 5-HT and NE sprouting in selected areas of neocortex, hippocampus and the subcortical limbic system. In parallel, we evaluate the role of antidepressants in enhancing neurotrophin expression and transduction in the same areas, focusing on BDNF and 5-HT reuptake inhibitors/enhancersx We subsequently test whether strategies that abolish BDNF expression/binding (such as blocking BDNF with antibodies and scavenging peptides or partially eliminating BDNF with transgenic approaches) inhibit the effects of antidepressants on 5-HT fiber sprouting. Finally, we assess the significance of trophic mechanisms for the mediation of antidepressant effects using BDNF +/- mice in laboratory models of depression. In concert, our proposal pursues a novel hypothesis for the effects of antidepressant drugs which has implications for an understanding of mood disorders as disorders of blunted structural plasticity of central monoamine systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SYNAPTIC HOMEOSTASIS IN DROSOPHILA Principal Investigator & Institution: Marrus, Scott B.; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Homeostatic mechanisms play an essential role in synaptic function. They are required for the stability of neural networks and play a role in learning and memory. It is suspected that they may compensate for various disease processes, such as myasthenia gravis, and might underlie the efficacy of drugs such as antidepressants. One model system in which homeostasis can be studied is the Drosophila neuromuscular junction. At this synapse, a decrease in the post-synaptic sensitivity to neurotransmitter results in a compensatory increase in pre-synaptic transmitter release. However, little is known about the nature or molecular components of this mechanism. It is not known whether the signal is synapse specific or a more global phenomenon, nor is it known whether this phenomenon occurs only during a critical period of development or also occurs at more mature synapses. The proposed experiments will elucidate these spatial and temporal features of this mechanism. The molecular mechanism will be further probed through the characterization of a novel mutation that disrupts this homeostatic response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
54
Antidepressants
•
Project Title: SYNTHESIS BENZAZEPINE
OF
FLUOXETINE
ANALOGS:
SUBSTITUTED
Principal Investigator & Institution: Okoro, Cosmas O.; Tennessee State University 3500 Centennial Blvd Nashville, Tn 37203 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: Fluoxetine (Prozac) is a commonly prescribed antidepressant that targets the serotonin transporter. Unlike tricyclics, such as imipramine, fluoxetine has little effect on other receptors, resulting in a lower occurrence of sedative and cardiovascular side effects. The semi-rigid sertraline (Zoloft) has a mechanism similar to fluoxetine, but is superior, because it confers lesser sedation than fluoxetine, in addition to being short acting. The primary objective of the present study is the design and synthesis of conformationally-restricted derivatives of fluoxetine, as potential pharmacologically active compounds. Both (R) and (S)-fluoxetine are flexible molecules. The (S)-isomer displays prolonged duration in man, which may contribute to side effects. Flexible molecules may have more than one site of action, with one preferred conformation at the receptor site. Side effects observed may be due to a low-energy conformation of fluoxetine at a second site. The synthesis of analogs in which the molecular framework of the pharmacophore is "locked" into semi-rigid form will allow a full study of the conformational aspects of drug action. The consideration of a benzazepine moiety in the proposed compounds was made in the light of cyclized version of norfluoxetine, which is active. Although amphetamines, cocaine and antidepressants profoundly affect human behavior, their underlyling mechanisms of action are unknown. It is postulated that the interactions of antidepressants with transporters account for the primary action of these drugs. The synthesized compounds will be used to study neurotransmitter uptake mechanisms, i.e. how transporters clear transmitters from the synaptic cleft after they are released from the nerve terminal. This part of the work will be done in colloboration with Dr. Louis J. DeFelice, Professor of Pharmacology and Neuroscience at Vanderbilt University School of Medicine. The research project will ultimately provide novel compounds for the treatment of depression and mental illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TELECOM ANTIDEPRESSANTS
SYSTEM
TO
IMPROVE
ADHERENCE
TO
Principal Investigator & Institution: Friedman, Robert H.; Director, Ambulatory Medicine; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 21-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The purpose of this pilot study is the development and preliminary evaluation of an automated telecommunications system to help adult patients with unipolar depression improve adherence to their antidepressant medication regimens and scheduled office visits with their mental health care providers. Based on Social Cognitive Theory (SCT), particularly its self-efficacy construct, the Telephone-Linked Care for Adherence to Treatment Regimen in Depression (TLCDepression) will automatically monitor adherence to treatment regimens as well as disease symptoms and functional status of patients and will give information, advice and counseling to patients to reinforce adherence. TLC-Depression will also generate reports from the information obtained from the patients and will communicate it to their mental health caregivers in order to assist the responsible physician in better monitoring of the patients medication-taking behavior, their depression symptoms and their
Studies
55
functioning. The study will entail 2 components: 1) A qualitative evaluation of TLCDepression that will be carried out with a maximum of 20 patients with the purpose of modification and refinement of the system. These patients will be screened for a period of 1 month to determine eligibility (medication adherence as measured by MEMS track caps less than 80 percent, and pill count audit). In-Depth interviews will be conducted twice a month with eligible subjects who will use TLC-Depression for 2 months. The results of the interviews will be utilized to improve and refine the intervention. 2) A quantitative pilot study to test TLC-Depression in order to utilize the system in a future randomized clinical trial with sufficient power to evaluate its efficacy. Sixty eligible patients will be randomized to the intervention (TLC) and usual care (UC) groups for a period of 4 months. All patients will be screened for a 1-month period to determine adherence eligibility (medication adherence as measured by MEMS track caps less than 80 percent, and pill count audit). Patients will call TLC-Depression and will converse with the system through the touch-tone keypad on their telephones. Patients will call TLC-Depression once a week at a scheduled time. The analysis will compare TLC and UC patients between baseline and follow-up 4 months later. Patients' self-efficacy, psychological and physical health status will be measured at baseline and at the end of the study. We hypothesize that TLC Depression will improve adherence, self-efficacy and psychological and physical health status among patients in the intervention group over a 4-month period in comparison with those in the control group. And that TLCDepression will be acceptable and usable by the patients Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF NITRIC OXIDE IN ANTIDEPRESSANT ACTIVITY Principal Investigator & Institution: Paul, Ian A.; University of Mississippi Medical Center 2500 N State St Jackson, Ms 39216 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2007 Summary: GRANT=6673590;P20RR Numerous laboratories have published evidence for a significant role of intracellular calcium homeostasis in major depressive disorders. Recent data implicates excitatory amino acid (EAA) neurotransmission in major depression and antidepressant activity. Synaptic activation at EAA receptive neurons is often mediated by the calcium-calmodulin-nitric oxide synthase-guanylyl cyclase cascade. We have recently demonstrated that antagonists of the several isoforms of nitric oxide synthase are as efficacious as imipramine in preclinical behavioral and biochemical screening procedures sensitive to antidepressants. We hypothesize that neuronal NOS inhibitors will produce antidepressant-like effects on behaviors and neurobiological sites know to be affected by antidepressants. Conversely, we hypothesize that the effects of clinically active SRI antidepressants on these behaviors and neurobiological sites is dependent upon their ability to inhibit neocortical NO production by NOS. Our SPECIFIC AIM 1 is to determine whether selective inhibition of nNOS will have antidepressant-like effects in mice. By extension of the central hypothesis, we predict that inhibition of neuronal NOS is absolutely required to produce the selective effects of antidepressants on behavior and neurobiological sites. Our SPECIFIC AIM 2 is to determine whether cotreatment with the nNOS substrate Larginine will disrupt the effects of known antidepressants on behavior and neurobiological adaptation. SPECIFIC AIM 3 will determine whether the effects of known antidepressants can proceed in mice lacking the nNOS isoform. Conversely, we hypothesize that lesion of monoaminergic neurons which modulate EAA signaling in forebrain will disrupt the ability of classical antidepressant but not neuronal NOS inhibitors to produce antidepressant-like effects in mice. Our SPECIFIC AIM 4 is to
56
Antidepressants
determine whether functional monoaminergic neurotransmitter systems are required for the antidepressant-like effects of NOS inhibitors. Finally, we hypothesize that antidepressant treatments will produce an adaptive response in EAA-receptive neurons utilizing nNOS as a subcellular messenger. Our SPECIFIC AIM 5 is to determine whether desensitization of neuronal NOS is produced by antidepressant treatments. We will test these hypotheses by examining the antidepressant-like effects of these treatments: (1) in acute behavioral tests and; (2) on neuronal substrates after chronic treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAPEUTIC NA+ CHANNEL BLOCKERS: RECEPTOR & DRUG DESIGN Principal Investigator & Institution: Wang, Ging K.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 31-JUL-2004 Summary: The long term objective of this renewal application is to develop therapeutic Na+ channel blockers pertinent to pain management. Traditional local anesthetics are often unsuited for treatment of chronic or intractable cancer pain because of their insufficient duration of nerve block. There are 4 specific aims: 1. To study the structureactivity relationship of various potent Na+ channel blockers in vitro; 2. To design and synthesize their amphipathic derivatives; 3. To test selected blockers suitable for prolonged nerve block in vivo; and 4. To map their receptor site within the Na+ channel alpha subunit. The first agent to be tested is the tricyclic antidepressant amitryptyline, which is a potent sodium channel blocking agent in addition to its actions at other receptors. With bupivacaine as a standard for comparison, the binding affinities of various tricyclics and other potent sodium channel blockers will be determined in voltage clamp studies on HEK cells transiently transfected with rat skeletal muscle and human heart sodium channel clones; native neuronal sodium channels in rat pituitary GH3 cells will also be used. Elements to be characterized include use-dependence of block and IC50 for resting and inactivated channel block. The working hypothesis for this phase of the studies is that duration of block in vivo will correlate positively with use dependence and negatively with IC50 for inactivated channel states. The in vivo studies will employ behavioral endpoints to examine both sensory and motor nerve block of sciatic nerve following a single injection of each agent in rats; drugs effective in rats will also be tested in the cauda equina space in sheep to model spinal routes of therapy. Drug design and synthesis will initially employ amitryptiline derivatives. Studies of the receptor site in the sodium channel will probe for the locations of two hydrophobic domains using point mutations and studies of drug potency on the mutated channels in HEK cells, with a special emphasis on residues which may be responsible for high-affinity binding of the tricyclic ring. Eventually the studies will be extended to other classes of drugs including phenylacetamides, calcium channel blockers, and a potassium channel blocker that also potently blocks sodium channels. Like tricyclic antidepressants, these agents have multiple phenyl rings but they are separated into two large hydrophobic domains rather than one. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: THYROID AXIS IN MAJOR DEPRESSION Principal Investigator & Institution: Ninan, Philip T.; Professor; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322
Studies
57
Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-JAN-2003 Summary: The goals of this proposal are to examine the relationship between Major Depressive Disorder (MDD) and abnormalities of the hypothalamic pituitary thyroid (HPT) axis. HPT abnormalities, specially subclinical hypothyroidism, are present in a significant number of patients with MDD. Yet the most common HPT abnormality reported in MDD is a blunted TSH response to TRH challenge suggesting central hyperactivity of the HPT axis. Perturbation of the normal functioning of the HPT axis is postulated to reflect central abnormality of TRH secretion which contribute to the heterogeneity of MDD, and plays a role in the response to antidepressant treatment. This application proposes to systematically examine the value of supplemental triiodothyronine (T3, Cytomel) with sertraline, a selective serotonin reuptake inhibitor (SSRI) in the treatment of MDD. The focus will be on two overlapping populations: 1) those with evidence of HPT abnormalities, and 2) those who did not respond to a previous adequate SSRI trial. This application proposes to programmatically develop a large study population of patients with MDD, classified with respect to HPT abnormalities and previous response to antidepressant treatment. The HPT axis will be systematically assessed in 200 patients with MDD and the benefit of triiodothyronine or placebo supplementation of sertraline examined. Half the study patients will have documented failure to a previous SSRI trial. The assessment of the HPT axis will include repeated peripheral baseline measures of TSH, total and free T3 and T4, antibodies to thyroglobulin and thyroid peroxidase; and the TRH stimulation test. Assessments will be repeated again after treatment. The primary hypothesis is that triiodothyronine supplementation sertraline will result in a greater improvement in HAM-D scores compared to placebo. Additional hypotheses will examine the role of HPT abnormalities and previous treatment response in the improvement to concomitant triiodothyronine with sertraline. This proposal is designed to provide a definitive clinical study of triiodothyronine augmentation of SSRI. It has the potential to significantly alter clinical practice in the management of MDD, particularly in patients who are non-responsive to antidepressants. The proposal will shed light on the role of the HPT axis in the pathophysiology and heterogeneity of MDD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSLATIONAL STUDIES OF DEPRESSION, PLATELETS, & CAD Principal Investigator & Institution: Badimon, Juan Jose.; Professor of Medicine; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Depressive symptoms significantly increase the risk of acute coronary syndromes recurrence (ACS). Platelet-thrombus formation over a disrupted atherosclerotic plaque is fundamental for ACS recurrence.Serotonin (5-HT) is an important stimulant of platelet reactivity. Increased 5-HT-mediated platelet reactivity due to upregulation of the platelet 5-HT2A receptor, increases thrombosis formation and has been postulated to a major mechanism linking depression to ACS recurrence. It is not known at this time if depression interventions reverse the increased risk of ACS events in depressed patients. The selective serotonin reuptake inhibitors (SSRIs) and the 5-HT2A receptor antidepressants improve depressive symptoms at equal rates. Both types of antidepressants may attenuate platelet reactivity by improving depressive symptoms (CNS mediated indirect effects). However, the SSRIs and the 5-HT2A receptor antagonists may have additional but divergent pharmacologic effects on platelet reactivity (direct platelet effects). Given the relationship between depression,
58
Antidepressants
platelet-thrombus formation, and the ACS, those antidepressants capable not only of improving depression symptoms but also of inhibiting platelet reactivity directly, may have the greatest net (direct + indirect) impact in inhibiting platelet-thrombus formation and preventing ACS events. A cross-sectional, case-control study will be conducted to compare 5-NT-mediated platelet reactivity and thrombosis between depressed and nondepressed patients with coronary artery disease (CAD) history. The direct in vitro effects of the SSRIs and 5-HT2A receptor antagonists will also be assessed. A randomized, 3 active arm, 1 control arm, depression intervention trial will be conducted to compare the in vivo net effects of pharmacologic (the SSRIs and 5-HT2A receptor antagonists) treatment and the indirect effects of a non-pharmacologic (cognitive behavioral therapy) treatment on platelet reactivity and thrombosis in depressed CAD patients. By defining differences in direct-platelet, CNS-mediated indirect, and net effects on platelet reactivity and thrombus formation, depression interventions that are best at inhibiting platelet reactivity and thrombogenicity can then be tested for reducing cardiovascular morbidity and mortality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF DEPRESSION AFTER CORONARY BYPASS SURGERY Principal Investigator & Institution: Freedland, Kenneth E.; Professor of Medical Psychology; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 29-JUN-2001; Project End 31-MAY-2005 Summary: (Adapted from investigator's abstract): Depression is a common and persistent problem after coronary artery bypass graft (CABG) surgery that complicates recovery, increases the risk of cardiac events, and may exacerbate the neurocognitive deficits that are often observed in post-CABG patients. Although CABG is one of the most frequently performed operations in the United States, there have not been any randomized, controlled trials of treatments for depression in this population. The aims of this study are (1) to compare the efficacy of cognitive behavior therapy (CBT), stress management (SM), and usual care (UC) for major depression following CABG surgery; (2) to determine the effects of CBT on neurocognitive performance, psychosocial adjustment, functional status, employment status, and health-related quality of life; and (3) to collect pilot data on the relationship between the treatment of depression and the 12-month incidence of cardiac and cerebrovascular events following CABG. Consenting patients will be screened for depression 4 to 6 weeks after surgery. Those who screen positive will return for a psycho-diagnostic evaluation and additional testing approximately 1 week later. A sample of 165 patients with major depression who meet all other eligibility criteria will be randomized to 12 weeks of CBT, SM, or UC with no restriction on non-study antidepressants. Participants in all 3 arms will be monitored for worsening depression and will be referred for additional care if needed. Depression outcomes will be assessed 12 weeks post-randomization and 6 months after surgery (2 months after termination of CBT or SM.) The primary hypothesis is that the posttreatment severity of depression is lower in patients treated with CBT than with SM or UC, with baseline depression severity and non-study treatment as planned covariates. Secondary analyses will test the effects of treatment on remission, neurocognitive and functional recovery, quality of life, and examine the relationships between treatment process and outcome variables. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
59
Project Title: TREATMENT OUTCOMES OF VASCULAR DEPRESSION Principal Investigator & Institution: Doraiswamy, Pudugramam; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): The treatment of major depression in late life (LLD) is an important health problem with a large and growing number of affected individuals. A significant subset of patients with LLD, particularly those with cerebrovascular risk factors (VRF)s, have subcortical gray matter (SCGMH) or frontal deep white matter (FDWMH) hyperintensities on brain mRI scans. Naturalistic studies suggest that such changes may be associated with poor acute and long-term antidepressant treatment response. However, the prognostic significance of brain MRI findings has not been evaluated systematically in prospective treatment trials. Similarly, studies have indicated that LLD patients frequently have deficits in Initiation/Perseveration (IP) and other tests of frontal lobe function. An elegant longitudinal study with nortriptyline has demonstrated that frontal executive dysfunction is associated with poor acute response as well as a greater risk for relapse/recurrence in LLD. However, the generalizability of this important finding to other classes of antidepressants, such as the widely used SSRIs, is not known. The interaction between frontal brain lesions and executive function deficits in LLD is also not fully studied. The proposed study will be the first large-scale prospective trial to simultaneously test the effects of both specific neuroanatomical and neuropsychological factors on course of response, remission rate as well as on broader measures of health outcomes in LLD. We propose to conduct a collaborative 12-week acute treatment trial with sertraline in 320 elderly (age greater than 60) patients with major depression at Duke University Medical Center and Washington University Medical Center. In a sample chosen to balance generalizability and scientific rigor, we will test the hypotheses that: 1) greater lesion severity on MRI will predict reduced treatment response, and 2) greater lesions severity on MRI willbe correlated with frontal executive dysfunction. In secondary aims, we will test the effects of lesion volume/location and frontal executive dysfunction on treatment response. In addition, we will test the effect of interactions of MRI-lesions, vascular risk factors and executive dysfunction on treatment response. The proposed trial will provide information of value to the practitioner and also provide data to build a more comprehensive model of the prognostic impact of frontal-subcortical brain changes on the outcome of late-life depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TRICYCLIC ANTIDEPRESSANTS AS RISKS FACTORS FOR CANCER Principal Investigator & Institution: Collet, Jean-Paul; Sir Mortimer B. Davis/Jewish Gen Hosp General Hospital Montreal, Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: Rational and Aims: Although mechanisms have not been confirmed, animal and epidemiological studies suggest that antidepressants promote tumor growth in humans. Recently, a study in animals showed that tricyclic antidepressants (TCAs) with a nitrogen atom at position 5 in the 7-membered ring of their chemical structure (5-N) were genotoxic, as compared to those with a carbon atom at the same position (5-C) (Van Schaik et al. Mutation Research 1993, 286(2): 155-163). These results were confirmed in humans by a large epidemiologic study (Sharpe et al. submitted to the
60
Antidepressants
British Journal of Cancer, 2000). In this historical population-based case-control study we will investigate the effect of past exposure to 5-N TCAs on the risk of developing cancer at 19 different sites. Methods: The source population for the study will be the dynamic cohort defined by membership in the Saskatchewan Prescription Drug Plan (SPDP). Incident cancer cases (at one of the 19 sites considered) over 5 years of age will be accrued by the provincial cancer registry from 1981 to 1999. At least 4 controls/case will be selected from the source population, matched on age, gender, and calendar time, using incidence density sampling. Detailed drug exposure data over a minimum of 5 years before diagnosis and up to a maximum of 23 years will be obtained from the SPDP. We will study for each drug and each site the respective effects of dosage, timing of use, and duration of use. Significance: If the results show that long-term use of antidepressants affect the incidence of cancer, they will be relevant to clinicians (with an elaboration on the risk/benefit profile of this therapy) and to the pharmaceutical industry (with a view to modifying the structure of drugs to enhance their beneficial effects and to reduce their harmful effects). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: USE OF ANTIDEPRESSANTS AND RISK OF BREAST CANCER Principal Investigator & Institution: Rossing, Mary A.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 13-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant): Diagnosis of depression is increasing in the United States, and women are twice as likely as men to suffer from depressive symptoms. With the advent of the selective serotonin reuptake inhibitors (SSRIs), antidepressant use has increased dramatically during the 1980s and 1990s, and the types of antidepressants prescribed have changed. Recent evidence that antidepressants can reduce the occurrence of menopausal hot flashes has led to predictions that antidepressant use may increase still further, particularly among women who are reluctant to take hormone replacement therapy due to concerns about breast cancer risk. Thus, better understanding of any possible role of antidepressants in breast cancer etiology is of substantial and growing public health importance. Initial concern about a role of antidepressants in human carcinogenesis was sparked by reports of increased occurrence of mammary tumors in rats administered tricyclic antidepressants or SSRIs. Epidemiologic findings have been inconsistent, but have not dispelled this concern. Two recent studies reported an elevated risk of breast cancer among users of some antidepressants; however, the class or type of antidepressant associated with increased risk differed. These studies were limited by the potential for error in self-reported drug use, and by relatively small numbers of exposed women. We propose to conduct a population-based, case control study to examine the association between antidepressant use and risk of breast cancer within the Group Health Cooperative of Puget Sound (GHC). Approximately 3,652 women diagnosed with first primary breast cancer (3,080 with invasive disease) during 1990-2000 and 7,304 randomly selected, matched controls will be included. Antidepressant use will be ascertained through the GHC pharmacy database, and information on potential confounding factors will be obtained from risk factor surveys routinely administered by GHC. The large study size and broad, recent interval of diagnosis years of cases will allow examination of the type, timing, and duration of use of antidepressants overall, classes of drugs (e.g., SSRIs or tricyclics), and individual drugs such as fluoxetine and paroxetine. Use of the pharmacy database will provide unbiased and complete exposure data relative to previous studies based on selfreported drug use.
Studies
61
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: USE EXTRACELLULAR 5 HT
OF
CHRONOAMPEROMETRY
TO
MEASURE
Principal Investigator & Institution: Frazer, Alan; Professor and Department Chairman; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 31-MAR-2006 Summary: The main goal of this proposal is to study the functional consequences and mechanisms underlying antidepressant-induced down-regulation of the serotonin transporter (SERT) and norepinephrine transporter (NET). These proteins are the key cellular targets for drugs used in the treatment of depression. Our general hypothesis is that the time-dependent antidepressant-induced decrease in these transporters may be one of the crucial determinants of both why and when serotonergic and noradrenergic transmission is markedly enhanced, with consequent behavioral improvement. To study this, both time course and mechanistic studies will be carried out. Time course studies will correlate the time-dependent sertraline-induced changes in SERT density (as measured by quantitative autoradiography) with changes in the chronoamperometric signal caused by local application of 5-HT in brain. This will be done after cessation of treatment also. Non-linear regression techniques will be applied to the electrochemical signal to obtain Vmax and KT values for 5-HT clearance by the SERT. The time course of down-regulation of the NET caused not only by DMI but also reboxetine and venlafaxine, at doses producing steady-state serum levels at the low and high ends of its therapeutic range, will be examined, as will the time course of the return of NET binding sites after cessation of treatment. At times when NET binding sites are downregulated, function of the NET will be assessed by measuring the uptake of 3H-NE in synaptosomes. Different approaches will be used to examine the mechanisms involved in these phenomena. We will study the time course of changes in mRNA for the SERT and its binding sites and mRNA for the NET and its binding sites during treatment of rats with antidepressants and after their cessation. We will study if chronic treatment of rats with uptake inhibitors either alters the distribution or decreases SERT or NET protein in purified membrane fractions obtained from brain. Purified membrane fractions will be obtained by ultracentrifugation of membranes layered on a sucrose gradient and the amount of SERT or NET protein in these fractions measured by Western blot analysis with specific antibodies. Knockout mice will be used to determine influences of PKC epsilon on antidepressant-induced down-regulation of the SERT and NET. Mice lacking 5-HT1B receptors will be used to see if they exhibit altered sertralineinduced down-regulation of the SERT. These experiments involve multiple approaches to study an effect of specific antidepressant drugs that may be very important in sustaining the enhancement of monoaminergic transmission that underlies clinical improvement Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VULVAR VESTIBULITIS TRIAL: DESIPRAMINE-LIDOCAINE Principal Investigator & Institution: Foster, David; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Studies are proposed for the subtype of vulvodynia known as vulvar vestibulitis. The first major aim of this application is to conduct a
62
Antidepressants
randomized, placebo-controlled, double-blinded clinical trial to study the clinical efficacy of four medical regimens: topical lidocaine, oral desipramine, topical lidocaine combined with oral desipramine and placebo. The efficacy of standard treatments for vulvar vestibulitis proven by randomized, placebo-controlled, blinded clinical trials has not been assessed. The tricyclic class of antidepressants, represented by desipramine, have gained empiric acceptance for the treatment of vulvar vestibulitis, although favorable therapeutic results have been reported by only a few retrospective studies or uncontrolled clinical trials. Although the precise mechanism of action remains undefined for tricyclic antidepressants, a "central" action through the dorsal horn and brain stem has been suggested. In contrast to oral desipramine, the long-term, topical application of lidocaine may act through a "local" mechanism. This randomized, placebo-controlled, double-blinded clinical trial is designed to determine whether "local" or "centrally-acting" treatments alone, or in combination are efficacious in treating vulvar vestibulitis. Outcome measures of success will include reduced overall pain, reduced pain to touch, reduced pain to standardized mechanical stimuli, increased painfree intercourse, improved sexual function, improved quality-of-life as measured by psychometric tests, and adherence to active drug regimens. The second major aim of this application is to study the relationship among genetic polymorphisms of the IL-1 Receptor Antagonist locus, tissue levels of pro-inflammatory cytokines, and response to treatment of vulvar vestibulitis. Pro-inflammatory cytokines, such as interleukin-I beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), are secreted from a local cellular source and accumulate above normal levels in the region of the hymeneal ring. Recent genetic analysis finds a 53% homozygosity for allele 2 IL-1 Receptor Antagonist (IL-1 RA*2) in cases of vulvar vestibulitis, in contrast to 8.5% homozygosity in asymptomatic women. Furthermore, the IL-1 RA*2 allele has been linked to increased production of IL-1 beta in vitro. In our second aim, we will determine whether these in vitro results can be extrapolated to clinical cases of vulvar vestibulitis. Using samples from our clinical trial, we will assess the relationship between homozygosity for IL-1 RA*2, tissue levels of IL-1 beta, and TNF-alpha, and response to treatment. In summary, this project will allow us to answer several important questions about vulvar vestibulitis. Is medical treatment effective? Is centrally-acting or locally-acting treatment equally effective or is one superior to the other? Is there any benefit from combined local and systemic treatments? And finally, do genetic characteristics and tissue cytokine concentrations influence treatment response? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “antidepressants” (or synonyms) into the search box. This search gives you access 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
Studies
63
to full-text articles. The following is a sample of items found for antidepressants in the PubMed Central database: •
Antidepressant- and Cocaine-Sensitive Human Serotonin Transporter: Molecular Cloning, Expression, and Chromosomal Localization. by Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD.; 1993 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46124
•
Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms. by Chilvers C, Dewey M, Fielding K, Gretton V, Miller P, Palmer B, Weller D, Churchill R, Williams I, Bedi N, Duggan C, Lee A, Harrison G.; 2001 Mar 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30555
•
Antidepressants and suicide: risk --benefit conundrums. by Healy D, Whitaker C.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=193979
•
Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care. by Hippisley-Cox J, Pringle M, Hammersley V, Crown N, Wynn A, Meal A, Coupland C.; 2001 Sep 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55927
•
Antidepressants in bipolar depression: when less is more. by Ruzickova M, Alda M.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161665
•
Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders. by Griebel G, Simiand J, Serradeil-Le Gal C, Wagnon J, Pascal M, Scatton B, Maffrand JP, Soubrie P.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122955
•
Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. by Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P.; 2003 May 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154757
•
Chronic Antidepressant Administration Decreases the Expression of Tyrosine Hydroxylase in the Rat Locus Coeruleus. by Nestler EJ, McMahon A, Sabban EL, Tallman JF, Duman RS.; 1990 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54779
•
Depression, antidepressants, and the shrinking hippocampus. by Sapolsky RM.; 2001 Oct 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60045
•
Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. by Peveler R, George C, Kinmonth AL, Campbell M, Thompson C.; 1999 Sep 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28214
•
Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and
64
Antidepressants
meta-analysis. by MacGillivray S, Arroll B, Hatcher S, Ogston S, Reid I, Sullivan F, Williams B, Crombie I.; 2003 May 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154760 •
Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. by Heisler LK, Chu HM, Brennan TJ, Danao JA, Bajwa P, Parsons LH, Tecott LH.; 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24573
•
Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. by Buckley NA, McManus PR.; 2002 Dec 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137809
•
Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. by van Walraven C, Mamdani MM, Wells PS, Williams JI.; 2001 Sep 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55923
•
Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review. by Furukawa TA, McGuire H, Barbui C.; 2002 Nov 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=131022
•
Neuroprotective effects of antidepressant and mood stabilizing drugs. by Young LT.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149791
•
Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. by Mynors-Wallis LM, Gath DH, Day A, Baker F.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27250
•
Reducing prescribing of highly anticholinergic antidepressants for elderly people: randomised trial of group versus individual academic detailing. by van Eijk ME, Avorn J, Porsius AJ, de Boer A.; 2001 Mar 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26547
•
Role of the Neurotransmitter Reuptake-Blocking Activity of Antidepressants in Reversing Chloroquine Resistance In Vitro in Plasmodium falciparum. by Taylor D, Walden JC, Robins AH, Smith PJ.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90136
•
Stress and Antidepressants Differentially Regulate Neurotrophin 3 mRNA Expression in the Locus Coeruleus. by Smith MA, Makino S, Altemus M, Michelson D, Hong S, Kvetnansky R, Post RM.; 1995 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41052
•
Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. by Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E.; 2001 Oct 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60133
Studies
•
65
The neurobiology of treatment response toantidepressants and mood stabilizing medications. by Young LT, Bakish D, Beaulieu S.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161660
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with antidepressants, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “antidepressants” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for antidepressants (hyperlinks lead to article summaries): •
A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants. Author(s): DeBattista C, Solvason HB, Poirier J, Kendrick E, Schatzberg AF. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544372&dopt=Abstract
•
A self-controlled, naturalistic study of selective serotonin reuptake inhibitors versus tricyclic antidepressants. Author(s): Faravelli C, Cosci F, Ciampelli M, Scarpato MA, Spiti R, Ricca V. Source: Psychotherapy and Psychosomatics. 2003 March-April; 72(2): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601227&dopt=Abstract
•
A time-series analysis of the effect of increased copayments on the prescription of antidepressants, anxiolytics, and sedatives in Sweden from 1990 to 1999. Author(s): Ong M, Catalano R, Hartig T. Source: Clinical Therapeutics. 2003 April; 25(4): 1262-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809972&dopt=Abstract
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
66
Antidepressants
•
Adverse drug reactions associated with antipsychotics, antidepressants, and mood stabilizers. Author(s): Antai-Otong D. Source: Nurs Clin North Am. 2003 March; 38(1): 161-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712677&dopt=Abstract
•
Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Author(s): Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M. Source: Biological Psychiatry. 2003 July 1; 54(1): 70-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842310&dopt=Abstract
•
An analysis of the diffusion of new antidepressants: variety, quality, and marketing efforts. Author(s): Berndt ER, Bhattacharjya A, Mishol DN, Arcelus A, Lasky T. Source: The Journal of Mental Health Policy and Economics. 2002 March; 5(1): 3-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529566&dopt=Abstract
•
Analgesic effects of antidepressants. Author(s): Fishbain DA. Source: The Journal of Clinical Psychiatry. 2003 January; 64(1): 96; Author Reply 96-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590632&dopt=Abstract
•
Antidepressant prescribing and suicide: Antidepressants do not reduce suicide rates. Author(s): Ankarberg PH. Source: Bmj (Clinical Research Ed.). 2003 August 2; 327(7409): 288-9; Author Reply 289. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12896950&dopt=Abstract
•
Antidepressants and antipsychotics in the long-term treatment of bipolar disorder. Author(s): Kusumakar V. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 10: 23-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392350&dopt=Abstract
•
Antidepressants and driver impairment: empirical evidence from a standard on-theroad test. Author(s): Ramaekers JG. Source: The Journal of Clinical Psychiatry. 2003 January; 64(1): 20-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590619&dopt=Abstract
Studies
67
•
Antidepressants and emotional processing. Author(s): Nathan PJ, Kemp AH, Harrison BJ. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 July; 28(7): 1383; Author Reply 1384-5. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784110&dopt=Abstract
•
Antidepressants and gene expression profiling: how to SNARE novel drug targets. Author(s): Lesch KP, Schmitt A. Source: The Pharmacogenomics Journal. 2002; 2(6): 346-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629500&dopt=Abstract
•
Antidepressants and risk of cancer: a case of misguided associations and priorities. Author(s): Theoharides TC, Konstantinidou A. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544368&dopt=Abstract
•
Antidepressants and somatic symptoms: therapeutic actions are expanding beyond affective spectrum disorders to functional somatic syndromes. Author(s): Stahl SM. Source: The Journal of Clinical Psychiatry. 2003 July; 64(7): 745-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934972&dopt=Abstract
•
Antidepressants and the risk of breast cancer. Author(s): Kurdyak PA, Gnam WH, Streiner DL. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 December; 47(10): 966-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553133&dopt=Abstract
•
Antidepressants for chronic neuropathic pain. Author(s): Reisner L. Source: Current Pain and Headache Reports. 2003 February; 7(1): 24-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525267&dopt=Abstract
•
Antidepressants for cocaine dependence. Author(s): Lima MS, Reisser AA, Soares BG, Farrell M. Source: Cochrane Database Syst Rev. 2003; (2): Cd002950. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804445&dopt=Abstract
68
Antidepressants
•
Antidepressants for generalized anxiety disorder. Author(s): Kapczinski F, Lima MS, Souza JS, Schmitt R. Source: Cochrane Database Syst Rev. 2003; (2): Cd003592. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804478&dopt=Abstract
•
Antidepressants for irritable bowel syndrome. Author(s): Clouse RE. Source: Gut. 2003 April; 52(4): 598-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631677&dopt=Abstract
•
Antidepressants for smoking cessation. Author(s): Hughes JR, Stead LF, Lancaster T. Source: Cochrane Database Syst Rev. 2003; (2): Cd000031. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804385&dopt=Abstract
•
Antidepressants for the treatment of depression in people with schizophrenia: a systematic review. Author(s): Whitehead C, Moss S, Cardno A, Lewis G. Source: Psychological Medicine. 2003 May; 33(4): 589-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785461&dopt=Abstract
•
Antidepressants in general practice. Author(s): Foxhill D. Source: Aust Fam Physician. 2003 July; 32(7): 486, 488. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901196&dopt=Abstract
•
Antidepressants in the treatment of migraine headache. Author(s): Punay NC, Couch JR. Source: Current Pain and Headache Reports. 2003 February; 7(1): 51-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525271&dopt=Abstract
•
Antidepressants: update on new agents and indications. Author(s): Ables AZ, Baughman OL 3rd. Source: American Family Physician. 2003 February 1; 67(3): 547-54. Review. Erratum In: Am Fam Physician. 2003 May 1; 67(9): 1874. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588077&dopt=Abstract
•
Are antidepressants effective in fibromyalgia? Author(s): Thomas E, Blotman F. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 December; 69(6): 531-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537258&dopt=Abstract
Studies
69
•
Assessment of the contributions of CYP3A4 and CYP3A5 in the metabolism of the antipsychotic agent haloperidol to its potentially neurotoxic pyridinium metabolite and effect of antidepressants on the bioactivation pathway. Author(s): Kalgutkar AS, Taylor TJ, Venkatakrishnan K, Isin EM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 March; 31(3): 243-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584149&dopt=Abstract
•
'Atypical' antidepressants in overdose: clinical considerations with respect to safety. Author(s): Buckley NA, Faunce TA. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2003; 26(8): 539-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825968&dopt=Abstract
•
Behavioral effects of delta-opioid receptor agonists: potential antidepressants? Author(s): Broom DC, Jutkiewicz EM, Rice KC, Traynor JR, Woods JH. Source: Japanese Journal of Pharmacology. 2002 September; 90(1): 1-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396021&dopt=Abstract
•
Cardiovascular effects of selective serotonin reuptake inhibitors and other novel antidepressants. Author(s): Khawaja IS, Feinstein RE. Source: Heart Disease. 2003 March-April; 5(2): 153-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713682&dopt=Abstract
•
Changes in paracetamol, antidepressants and opioid poisoning in Scotland during the 1990s. Author(s): Bateman DN, Bain M, Gorman D, Murphy D. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 February; 96(2): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589010&dopt=Abstract
•
Channelling new antidepressants to problem patients may be factor in fatal toxicity. Author(s): Heerdink ER, Hugenholtz GW, Meijer WE, Egberts AC. Source: Bmj (Clinical Research Ed.). 2003 March 15; 326(7389): 600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637414&dopt=Abstract
•
Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Author(s): Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G. Source: The American Journal of Psychiatry. 2002 November; 159(11): 1889-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411224&dopt=Abstract
70
Antidepressants
•
Chronic treatment with antidepressants decreases intraoperative core hypothermia. Author(s): Kudoh A, Takase H, Takazawa T. Source: Anesthesia and Analgesia. 2003 July; 97(1): 275-9, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818981&dopt=Abstract
•
Clinical implications of antidepressant and stimulant use on switching from depression to mania in children. Author(s): Craney J, Geller B. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Summer; 13(2): 2014. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880514&dopt=Abstract
•
Clinical indicators for the use of antidepressants in the treatment of bipolar I depression. Author(s): Fagiolini A, Frank E, Cherry CR, Houck PR, Novick DM, Buysse DJ, Kupfer DJ. Source: Bipolar Disorders. 2002 October; 4(5): 277-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479658&dopt=Abstract
•
Comparing the methods used to compare antidepressants. Author(s): Thase ME. Source: Psychopharmacology Bulletin. 2002 Spring; 36 Suppl 1: Suppl 1-17; Quiz Suppl 18-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395691&dopt=Abstract
•
Differential effects of antidepressants on glucocorticoid receptors in human primary blood cells and human monocytic U-937 cells. Author(s): Heiske A, Jesberg J, Krieg JC, Vedder H. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 April; 28(4): 807-17. Epub 2002 September 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655328&dopt=Abstract
•
Discontinuation of antidepressants in newly admitted psychotic patients. Author(s): Bowers MB Jr, McKay BG, Mazure CM. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Spring; 15(2): 227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724466&dopt=Abstract
•
Do antidepressants induce rapid cycling? A gender-specific association. Author(s): Yildiz A, Sachs GS. Source: The Journal of Clinical Psychiatry. 2003 July; 64(7): 814-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934983&dopt=Abstract
Studies
71
•
Dual action antidepressants and some important considerations. Author(s): Gupta RK, Tiller JW, Burrows GD. Source: The Australian and New Zealand Journal of Psychiatry. 2003 April; 37(2): 190-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656958&dopt=Abstract
•
Dual NK(1) antagonists--serotonin reuptake inhibitors as potential antidepressants. Part 2: SAR and activity of benzyloxyphenethyl piperazine derivatives. Author(s): Ryckmans T, Berton O, Grimee R, Kogej T, Lamberty Y, Pasau P, Talaga P, Genicot C. Source: Bioorganic & Medicinal Chemistry Letters. 2002 November 4; 12(21): 3195-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372532&dopt=Abstract
•
Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Author(s): Sauer WH, Berlin JA, Kimmel SE. Source: Circulation. 2003 July 8; 108(1): 32-6. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821544&dopt=Abstract
•
Effectiveness of antidepressants: comparative remission rates. Author(s): Thase ME. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 2: 3-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625792&dopt=Abstract
•
Effects of antidepressants on cytokine production and actions. Author(s): Castanon N, Leonard BE, Neveu PJ, Yirmiya R. Source: Brain, Behavior, and Immunity. 2002 October; 16(5): 569-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401470&dopt=Abstract
•
Effects of antidepressants on function and viability of human neutrophils. Author(s): Strumper D, Durieux ME, Hollmann MW, Troster B, den Bakker CG, Marcus MA. Source: Anesthesiology. 2003 June; 98(6): 1356-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766643&dopt=Abstract
•
Effects of chronic antidepressants and electroconvulsive shock on serotonergic neurotransmission in the rat hippocampus. Author(s): Dremencov E, Gur E, Lerer B, Newman ME. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 August; 27(5): 729-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921903&dopt=Abstract
72
Antidepressants
•
Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis. Author(s): MacGillivray S, Arroll B, Hatcher S, Ogston S, Reid I, Sullivan F, Williams B, Crombie I. Source: Bmj (Clinical Research Ed.). 2003 May 10; 326(7397): 1014. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742924&dopt=Abstract
•
Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fracture. Author(s): Hubbard R, Farrington P, Smith C, Smeeth L, Tattersfield A. Source: American Journal of Epidemiology. 2003 July 1; 158(1): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835289&dopt=Abstract
•
Gender differences in the pharmacokinetics and pharmacodynamics of antidepressants. Author(s): Bies RR, Bigos KL, Pollock BG. Source: J Gend Specif Med. 2003; 6(3): 12-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513571&dopt=Abstract
•
How could antidepressants worsen unipolar depression? Author(s): Benazzi F. Source: Psychotherapy and Psychosomatics. 2003 March-April; 72(2): 107-8; Author Reply 109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601229&dopt=Abstract
•
Increased postoperative pain scores in chronic depression patients who take antidepressants. Author(s): Kudoh A, Katagai H, Takazawa T. Source: Journal of Clinical Anesthesia. 2002 September; 14(6): 421-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393109&dopt=Abstract
•
Indications for and use of antidepressants in child and adolescent psychiatry--a crosssectional survey in Denmark. Author(s): Buhl Sorensen C, Bohm Jepsen E, Thomsen PH, Dalsgaard S. Source: European Child & Adolescent Psychiatry. 2003 June; 12(3): 114-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768458&dopt=Abstract
Studies
73
•
Influence of antidepressants on intracellular levels of cyclic adenosine monophosphate in human peripheral blood mononuclear cells. Author(s): Kenis G, Steinbusch H, De Baets M, Maes M. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2003 January; 13(1): 53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480123&dopt=Abstract
•
Inhibition of P-glycoprotein by newer antidepressants. Author(s): Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 April; 305(1): 197-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649369&dopt=Abstract
•
Linezolid, a monoamine oxidase inhibiting antibiotic, and antidepressants. Author(s): Aga VM, Barklage NE, Jefferson JW. Source: The Journal of Clinical Psychiatry. 2003 May; 64(5): 609-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755668&dopt=Abstract
•
Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants. Author(s): Nierenberg AA, Papakostas GI, Petersen T, Montoya HD, Worthington JJ, Tedlow J, Alpert JE, Fava M. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544380&dopt=Abstract
•
Long-term side effects of newer-generation antidepressants: SSRIS, venlafaxine, nefazodone, bupropion, and mirtazapine. Author(s): Masand PS, Gupta S. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 2002 September; 14(3): 175-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585567&dopt=Abstract
•
Low dosage tricyclic antidepressants for depression. Author(s): Furukawa T, McGuire H, Barbui C. Source: Cochrane Database Syst Rev. 2003; (3): Cd003197. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917952&dopt=Abstract
•
Low dosage tricyclic antidepressants in depression. Evidence to change current guidelines is insufficient. Author(s): Ali IM. Source: Bmj (Clinical Research Ed.). 2003 March 1; 326(7387): 499; Author Reply 499. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617073&dopt=Abstract
74
Antidepressants
•
Low dosage tricyclic antidepressants in depression. Giving low dose tricyclics is not justified by evidence. Author(s): Jones HM. Source: Bmj (Clinical Research Ed.). 2003 March 1; 326(7387): 499; Author Reply 499. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609953&dopt=Abstract
•
Low dosage tricyclic antidepressants in depression. Non-superiority does not equal equivalence. Author(s): Martin JE. Source: Bmj (Clinical Research Ed.). 2003 March 1; 326(7387): 499; Author Reply 499. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617074&dopt=Abstract
•
Low-dose risperidone augmentation of antidepressants in nonpsychotic depressive disorders with suicidal ideation. Author(s): Viner MW, Chen Y, Bakshi I, Kamper P. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 104-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544386&dopt=Abstract
•
Managing weight gain as a side effect of antidepressant therapy. Author(s): Deshmukh R, Franco K. Source: Cleve Clin J Med. 2003 July; 70(7): 614, 616, 618, Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882383&dopt=Abstract
•
Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review. Author(s): Furukawa TA, McGuire H, Barbui C. Source: Bmj (Clinical Research Ed.). 2002 November 2; 325(7371): 991. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411354&dopt=Abstract
•
New approaches to developing antidepressants by enhancing monoaminergic neurotransmission. Author(s): Bymaster FP, McNamara RK, Tran PV. Source: Expert Opinion on Investigational Drugs. 2003 April; 12(4): 531-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665410&dopt=Abstract
•
New directions in the development of antidepressants: the interface of neurobiology and psychiatry. Author(s): Nemeroff CB. Source: Human Psychopharmacology. 2002 June; 17 Suppl 1: S13-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404664&dopt=Abstract
Studies
75
•
Old and new antidepressants: where are we? Author(s): Ayuso-Gutierrez JL. Source: World J Biol Psychiatry. 2002 July; 3(3): 112-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478875&dopt=Abstract
•
On the role of metabotropic glutamate receptors in the mechanisms of action of antidepressants. Author(s): Palucha A, Pilc A. Source: Polish Journal of Pharmacology. 2002 November-December; 54(6): 581-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866712&dopt=Abstract
•
Onset of action of antidepressants: results of different analyses. Author(s): Thompson C. Source: Human Psychopharmacology. 2002 June; 17 Suppl 1: S27-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404667&dopt=Abstract
•
Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebocontrolled trial. Author(s): Raja SN, Haythornthwaite JA, Pappagallo M, Clark MR, Travison TG, Sabeen S, Royall RM, Max MB. Source: Neurology. 2002 October 8; 59(7): 1015-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370455&dopt=Abstract
•
Predictors of response to antidepressants general principles and clinical implications. Author(s): Nierenberg AA. Source: The Psychiatric Clinics of North America. 2003 June; 26(2): 345-52, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778837&dopt=Abstract
•
Psychomotor development in children exposed in utero to benzodiazepines, antidepressants, neuroleptics, and anti-epileptics. Author(s): Mortensen JT, Olsen J, Larsen H, Bendsen J, Obel C, Sorensen HT. Source: European Journal of Epidemiology. 2003; 18(8): 769-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974552&dopt=Abstract
•
Reassessment of global benefit-risk assessment of antidepressants: venlafaxine XR and fluoxetine. Author(s): Tamura RN, Lu Y. Source: Journal of Psychiatric Research. 2003 March-April; 37(2): 175-6; Author Reply 176-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842172&dopt=Abstract
76
Antidepressants
•
Relapse prevention and antidepressants. Author(s): Curtin F, Schulz P. Source: Lancet. 2003 June 21; 361(9375): 2158-9; Author Reply 2159. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826459&dopt=Abstract
•
Relapse prevention and antidepressants. Author(s): Benazzi F. Source: Lancet. 2003 June 21; 361(9375): 2158; Author Reply 2159. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826458&dopt=Abstract
•
Relative risk of vaginal candidiasis after use of antibiotics compared with antidepressants in women: postmarketing surveillance data in England. Author(s): Wilton L, Kollarova M, Heeley E, Shakir S. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2003; 26(8): 589-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825971&dopt=Abstract
•
Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. Author(s): Whyte IM, Dawson AH, Buckley NA. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 May; 96(5): 369-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702786&dopt=Abstract
•
REM sleep effects as a biomarker for the effects of antidepressants in healthy volunteers. Author(s): Rijnbeek B, de Visser SJ, Franson KL, Cohen AF, van Gerven JM. Source: Journal of Psychopharmacology (Oxford, England). 2003 June; 17(2): 196-203. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870567&dopt=Abstract
•
Risk of drug interaction: combination of antidepressants and other drugs. Author(s): Miyasaka LS, Atallah AN. Source: Revista De Saude Publica. 2003 April; 37(2): 212-5. Epub 2003 April 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700843&dopt=Abstract
•
Safety of antidepressants in the elderly. Author(s): Sommer BR, Fenn H, Pompei P, DeBattista C, Lembke A, Wang P, Flores B. Source: Expert Opinion on Drug Safety. 2003 July; 2(4): 367-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904093&dopt=Abstract
Studies
77
•
Signify ER Drug Screen Test evaluation: comparison to Triage Drug of Abuse Panel plus tricyclic antidepressants. Author(s): Phillips JE, Bogema S, Fu P, Furmaga W, Wu AH, Zic V, Hammett-Stabler C. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 February; 328(1-2): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559596&dopt=Abstract
•
Stress, metaplasticity, and antidepressants. Author(s): Garcia R. Source: Current Molecular Medicine. 2002 November; 2(7): 629-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420802&dopt=Abstract
•
Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Author(s): Khan A, Khan S, Kolts R, Brown WA. Source: The American Journal of Psychiatry. 2003 April; 160(4): 790-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668373&dopt=Abstract
•
Switch to mania upon discontinuation of antidepressants in patients with mood disorders: a review of the literature. Author(s): Ali S, Milev R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 May; 48(4): 258-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776393&dopt=Abstract
•
Switching, cycling, and antidepressant-induced effects on cycle frequency and course of illness in adult bipolar disorder: a brief review and commentary. Author(s): Papolos DF. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Summer; 13(2): 16571. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880510&dopt=Abstract
•
The development of new antidepressants: focus on duloxetine and escitalopram. Author(s): Huffman JC, Perlis RH. Source: Harvard Review of Psychiatry. 2003 January-February; 11(1): 30-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866739&dopt=Abstract
•
The effect of antidepressants on serum melatonin levels in endogenous depression. Author(s): Varma A, Kaul RK, Varma P, Kalra V, Malhotra V. Source: J Assoc Physicians India. 2002 October; 50: 1262-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568211&dopt=Abstract
78
Antidepressants
•
The efficacy of antidepressants in the treatment of depression in dementia. Author(s): Bains J, Birks JS, Dening TR. Source: Cochrane Database Syst Rev. 2002; (4): Cd003944. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519625&dopt=Abstract
•
The new generation of antidepressants. Author(s): Diab T, Singh AN. Source: Hosp Med. 2003 January; 64(1): 12-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572328&dopt=Abstract
•
The toxicity of antidepressant poisoning: is it changing? A comparative study of cyclic and newer serotonin-specific antidepressants. Author(s): Graudins A, Dowsett RP, Liddle C. Source: Emergency Medicine (Fremantle, W.A.). 2002 December; 14(4): 440-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534489&dopt=Abstract
•
The use of antidepressants in alcohol-dependent veterans. Author(s): Petrakis IL, Leslie D, Rosenheck R. Source: The Journal of Clinical Psychiatry. 2003 August; 64(8): 865-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926999&dopt=Abstract
•
The use of antidepressants in novel combination therapies. Author(s): Shelton RC. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 2: 14-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625794&dopt=Abstract
•
Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions? Author(s): Muller MJ, Dragicevic A, Fric M, Gaertner I, Grasmader K, Hartter S, Hermann E, Kuss HJ, Laux G, Oehl W, Rao ML, Rollmann N, Weigmann H, WeberLabonte M, Hiemke C. Source: Pharmacopsychiatry. 2003 May; 36(3): 98-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806567&dopt=Abstract
•
Tricyclic antidepressants and fibromyalgia: what is the mechanism of action? Author(s): Lawson K. Source: Expert Opinion on Investigational Drugs. 2002 October; 11(10): 1437-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387704&dopt=Abstract
Studies
79
•
Tricyclic antidepressants as long-acting local anesthetics. Author(s): Sudoh Y, Cahoon EE, Gerner P, Wang GK. Source: Pain. 2003 May; 103(1-2): 49-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749958&dopt=Abstract
•
Tricyclic antidepressants prevent the differentiation of monocytes into macrophagelike cells in vitro. Author(s): Ying G, Karlsson H, DePierre JW, Nassberger L. Source: Cell Biology and Toxicology. 2002; 18(6): 425-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484552&dopt=Abstract
•
Underuse of antidepressants. Author(s): Patten SB, Beck CA. Source: The American Journal of Psychiatry. 2003 January; 160(1): 189-90; Author Reply 190. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505834&dopt=Abstract
•
Use of antidepressants by general practitioners and psychiatrists in Australia. Author(s): McManus P, Mant A, Mitchell P, Britt H, Dudley J. Source: The Australian and New Zealand Journal of Psychiatry. 2003 April; 37(2): 184-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656957&dopt=Abstract
•
Use of dosage as a triage guideline for unintentional cyclic antidepressant (UCA) ingestions in children. Author(s): Spiller HA, Baker SD, Krenzelok EP, Cutino L. Source: The American Journal of Emergency Medicine. 2003 September; 21(5): 422-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523882&dopt=Abstract
81
CHAPTER 2. NUTRITION AND ANTIDEPRESSANTS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and antidepressants.
Finding Nutrition Studies on Antidepressants The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “antidepressants” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
82
Antidepressants
The following is a typical result when searching for recently indexed consumer information on antidepressants: •
A comparative analysis of standard and alternative antidepressants in the treatment of human immunodeficiency virus patients. Author(s): New York State Psychiatric Institue, NY 10032, USA. Source: Wagner, G J Rabkin, J G Rabkin, R Compr-Psychiatry. 1996 Nov-December; 37(6): 402-8 0010-440X
•
A double blind, randomized clinical trial assessing the efficacy and safety of augmenting standard antidepressant therapy with nimodipine in the treatment of 'vascular depression'. Author(s): Geriatric Neuropsychiatry Group, CEMIC University, Buenos Aires, Argentina. Source: Taragano, F E Allegri, R Vicario, A Bagnatti, P Lyketsos, C G Int-J-GeriatrPsychiatry. 2001 March; 16(3): 254-60 0885-6230
•
An open study of triiodothyronine augmentation of tricyclic antidepressants in inpatients with refractory depression. Author(s): Department of Biological Psychiatry, Psychiatric Centre Bloemendaal, The Hague, The Netherlands. Source: Birkenhager, T K Vegt, M Nolen, W A Pharmacopsychiatry. 1997 January; 30(1): 23-6 0176-3679
•
Antagonism by tricyclic antidepressants of the muscarinic receptors located on the adrenergic nerve endings in rabbit heart atrium. Author(s): Western Psychiatric Institute and Clinic, University of Pittsburgh, Pennsylvania. Source: Somogyi, G T Perel, J M J-Pharmacol-Exp-Ther. 1989 December; 251(3): 922-8 0022-3565
•
Antidepressant activity of S-adenosyl-L-methionine in mice and rats. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow. Source: Czyrak, A Rogoz, Z Skuza, G Zajaczkowski, W Maj, J J-Basic-Clin-PhysiolPharmacol. 1992 Jan-March; 3(1): 1-17 0792-6855
•
Antidepressant drug therapy: associated risks. Author(s): Department of PKF/TN, F. Hoffmann-La Roche & Co., Ltd., Basle, Switzerland. Source: Amrein, R Allen, S R Vranesic, D Stabl, M J-Neural-Transm-Suppl. 1988; 2673-86 0303-6995
•
Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction. Author(s): Department of Pharmacology, Imperial College School of Medicine, P.O. Box 8751, London W13 8WH, UK.
[email protected] Source: Montgomery, S A Baldwin, D S Riley, A J-Affect-Disord. 2002 May; 69(1-3): 11940 0165-0327
•
Antidepressants and thyroid hormone levels. Author(s): Mood Disorders Program, Clarke Institute of Psychiatry, Toronto, Ontario, Canada. Source: Joffe, R T Singer, W Acta-Med-Austriaca. 1992; 19 Suppl 196-7 0303-8173
•
Antidepressants given repeatedly increase the behavioural effect of dopamine D-2 agonist. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Nutrition
83
Source: Maj, J Rogoz, Z Skuza, G Sowinska, H J-Neural-Transm-Gen-Sect. 1989; 78(1): 18 0300-9564 •
Antidepressants in cancer pain. Author(s): Department of Pharmacology, School of Medicine, University of Milan, Italy. Source: Panerai, A E Bianchi, M Sacerdote, P Ripamonti, C Ventafridda, V De Conno, F J-Palliat-Care. 1991 Winter; 7(4): 42-4 0825-8597
•
Association of antidepressants and other medications with mortality in the residential-care elderly. Author(s): Department of Psychiatry, University of Pennsylvania, Philadelphia Geriatric Center 19104. Source: Katz, I R Parmelee, P A Beaston Wimmer, P Smith, B D J-Geriatr-PsychiatryNeurol. 1994 Oct-December; 7(4): 221-6 0891-9887
•
Differential effects of clonidine, lithium and quinine in the forced swimming test in mice for antidepressants: possible roles of serotoninergic systems. Author(s): GIS Medicament, Department of Pharmacology, Faculty of Medicine, Nantes, France. Source: Bourin, M Hascoet, M Colombel, M C Redrobe, J P Baker, G B EurNeuropsychopharmacol. 1996 August; 6(3): 231-6 0924-977X
•
Differential regulation of neuropeptide Y mRNA expression in the arcuate nucleus and locus coeruleus by stress and antidepressants. Author(s): Clinical Neuroendocrinology Branch; Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1284, USA. Source: Makino, S Baker, R A Smith, M A Gold, P W J-Neuroendocrinol. 2000 May; 12(5): 387-95 0953-8194
•
Direct influence of antidepressants on GTP binding protein of adenylate cyclase in cell membranes of the cerebral cortex of rats. Author(s): Department of Neuropsychiatry, Fujita-Gakuen Health University, School of Medicine, Aichi, Japan. Source: Yamaoka, K Nanba, T Nomura, S J-Neural-Transm. 1988; 71(3): 165-75 0300-9564
•
Does higher cardiovascular response to ECT predict early antidepressant effect? Author(s): Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, 560 India. Source: Saravanan, E S Gangadhar, B N Janakiramaiah, N Pandey, R S Murthy, H S Subbakrishna, D K J-Affect-Disord. 2002 May; 69(1-3): 101-8 0165-0327
•
Does sodium valproate increase clinical effects of antidepressants? Author(s): Inst. Organic Chemistry and Biochemistry, Czechosl. Acad. Sci., Prague. Source: Vinar, O Dvorak, A Obrovska, V Kriskova, M Turcek, K Act-Nerv-Super(Praha). 1989 June; 31(2): 103-5 0001-7604
•
Effects of antidepressants on thyroid stimulating hormone release in rats under ether stress. Author(s): Department of Psychiatry, Kobe University Medical School, Japan. Source: Kadono, Y Kaneda, H Maeda, K Psychiatry-Clin-Neurosci. 1995 August; 49(4): 231-6 1323-1316
•
Effects of chronic antidepressant treatment on alpha 1- and alpha 2-adrenoceptors in the rat anococcygeus muscle. Author(s): Department de Farmacologia i Psiquiatria, Universitat Autonoma de Barcelona, Bellaterra, Spain. Source: Vila, E Salles, J Badia, A J-Neural-Transm-Gen-Sect. 1990; 82(3): 205-12 0300-9564
84
Antidepressants
•
Effects of chronic treatment with lithium and antidepressants on [3H]forskolin binding to rat cerebral cortical membranes. Author(s): Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo. Source: Odagaki, Y Koyama, T Yamashita, I Jpn-J-Psychiatry-Neurol. 1991 March; 45(1): 125-6 0912-2036
•
Effects of subchronic administration of antidepressants and anxiolytics on levels of the alpha subunits of G proteins in the rat brain. Author(s): Department of Psychiatry, College of Medicine, University of Illinois at Chicago, USA. Source: Dwivedi, Y Pandey, G N J-Neural-Transm. 1997; 104(6-7): 747-60
•
Hypericum perforatum extracts as potential antidepressants. Author(s): National Institute of Mental Health, Bethesda, MD, USA.
[email protected] Source: Vitiello, B J-Pharm-Pharmacol. 1999 May; 51(5): 513-7 0022-3573
•
Influence of antidepressant drugs on seizure susceptibility and the anticonvulsant activity of valproate in mice. Author(s): Department of Pharmacology, Medical School, Lublin, Poland. Source: Kleinrok, Z Gustaw, J Czuczwar, S J J-Neural-Transm-Suppl. 1991; 3485-90 03036995
•
Influence of changes in protein binding on the central activity of antidepressants. Author(s): Department of Pharmacology, Faculty of Medicine, Basque Country, Leioa, Vizcaya, Spain. Source: Torres, I Gomez, E Garcia, E Suarez, E Rodriguez Sasiain, J M Calvo, R J-PharmPharmacol. 1992 June; 44(6): 531-3 0022-3573
•
Influence of food intake on the bioavailability of zimeldine and its active metabolite, norzimeldine [Antidepressants]. Source: Wahlen, A. Westerlund, D. Wahlin Boll, E. Melander, A. Drug-Nutr-Interact. New York : Alan R. Liss. 1983. volume 2 (3) page 175-181. 0272-3530
•
Inhibition of acid secretion in guinea pigs by tricyclic antidepressants: comparison with ranitidine and omeprazole. Author(s): Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Source: Batzri, S Brugada, O Harmon, J W Rich, N M J-Pharmacol-Exp-Ther. 1988 August; 246(2): 493-9 0022-3565
•
Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo. Author(s): Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts. Source: von Moltke, L L Greenblatt, D J Cotreau Bibbo, M M Duan, S X Harmatz, J S Shader, R I J-Pharmacol-Exp-Ther. 1994 March; 268(3): 1278-83 0022-3565
•
Inhibitory effects of antidepressants on NMDA-induced currents in Xenopus oocytes injected with rat brain RNA. Author(s): Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. Source: Tohda, M Urushihara, H Nomura, Y Neurochem-Int. 1995 January; 26(1): 53-8 0197-0186
Nutrition
85
•
Involvement of metabolites in the inhibitory effects of 2-(4-ethyl-1-piperazinyl)-4phenylquinoline dimaleate (AD-2646), a new quinoline derivative, on gastric acid secretion. A comparison with tricyclic antidepressants. Author(s): Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan. Source: Kimura, Y Yano, S Watanabe, K J-Pharmacobiodyn. 1989 January; 12(1): 43-9 0386-846X
•
Involvement of protein kinase in the regulation of beta-adrenergic receptors by antidepressants. Author(s): Department of Neuropsychiatry, St. Marianna University School of Medicine, Kanagawa, Japan. Source: Asakura, M Tsukamoto, T Kubota, H Osada, K Imafuku, J Nishizaki, J Sato, A Nakanishi, J Shimbo, K Shibata, M et al. Int-J-Clin-Pharmacol-Res. 1989; 9(2): 123-30 0251-1649
•
Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late-life depression. Author(s): University Department of Old Age Psychiatry, Manchester Royal Infirmary. Source: Simpson, S Baldwin, R C Jackson, A Burns, A S Psychol-Med. 1998 September; 28(5): 1015-26 0033-2917
•
Isoniazid and antidepressants: is there cause for concern? Author(s): Fairfield Infectious Diseases Hospital, Australia. Source: Judd, F K Mijch, A M Cockram, A Norman, T R Int-Clin-Psychopharmacol. 1994 Summer; 9(2): 123-5 0268-1315
•
Liability in prescribing choice: the example of the antidepressants. Author(s): Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Australia. Source: Beerworth, E E Tiller, J W Aust-N-Z-J-Psychiatry. 1998 August; 32(4): 560-6 00048674
•
Lithium addition in endogenous depressions resistant to tricyclic antidepressants or related drugs: relation to the status of the pituitary-thyroid axis. Author(s): Psychiatric University Hospital, Zurich, Switzerland. Source: Schopf, J Lemarchand, T Pharmacopsychiatry. 1994 September; 27(5): 198-201 0176-3679
•
Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity. Author(s): Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Skovagervej 2, DK-8240 Risskov, Denmark.
[email protected] Source: Wegener, G Volke, V Harvey, B H Rosenberg, R Brain-Res. 2003 January 3; 959(1): 128-34 0006-8993
•
No alterations in the 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase activity in the hippocampal membranes from rats chronically treated with lithium or antidepressants. Author(s): Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan. Source: Odagaki, Y Koyama, T Yamashita, I J-Neural-Transm-Gen-Sect. 1991; 86(2): 8596 0300-9564
86
Antidepressants
•
Once daily sustained release tablets of venlafaxine, a novel antidepressant. Author(s): Pharmaceutical Division, Department of Chemical Technology (Autonomous), University of Mumbai, Nathalal Parikh Marg, Matunga, Mumbai400019, India. Source: Makhija, S N Vavia, P R Eur-J-Pharm-Biopharm. 2002 July; 54(1): 9-15 0939-6411
•
Pharmacokinetic patterns of repeated administration of antidepressants in animals. I. Implications for antinociceptive action of clomipramine in mice. Author(s): Laboratoire de Pharmacologie Medicale, INSERM U195, Faculte de Medecine, Clermont-Ferrand, France. Source: Eschalier, A Fialip, J Varoquaux, O Makambila, M C Marty, H Bastide, P JPharmacol-Exp-Ther. 1988 June; 245(3): 963-8 0022-3565
•
Pharmacokinetic patterns of repeated administration of antidepressants in animals. II. Their relevance in a study of the influence of clomipramine on morphine analgesia in mice. Author(s): Laboratoire de Pharmacologie et de Pharmacie Clinique, Faculte de Pharmacie, Clermont-Ferrand, France. Source: Fialip, J Marty, H Makambila, M C Civiale, M A Eschalier, A J-Pharmacol-ExpTher. 1989 February; 248(2): 747-51 0022-3565
•
Pharmacological effects of milnacipran, a new antidepressant, given repeatedly on the alpha1-adrenergic and serotonergic 5-HT2A systems. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow. Source: Maj, J Rogoz, Z Dlaboga, D Dziedzicka Wasylewska, M J-Neural-Transm. 2000; 107(11): 1345-59
•
Pharmacological effects of venlafaxine, a new antidepressant, given repeatedly, on the alpha 1-adrenergic, dopamine and serotonin systems. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. Source: Maj, J Rogoz, Z J-Neural-Transm. 1999; 106(2): 197-211
•
Plasma level of lithium in rats treated subchronically with lithium and tricyclic antidepressants. Author(s): P. Z. Dept. of Pharmacology and Toxicol., Faculty of Pharmacy, Charles Univ., Hradec Kralove, CSSR. Source: Zackova, P Krpalek, P Jaros, P Hajkova, L Act-Nerv-Super-(Praha). 1989 December; 31(4): 277-9 0001-7604
•
Randomized trial of opioids versus tricyclic antidepressants for radiation-induced mucositis pain in head and neck cancer. Author(s): Department of Oncology, Aarhus University Hospital, Denmark.
[email protected] Source: Ehrnrooth, E Grau, C Zachariae, R Andersen, J Acta-Oncol. 2001; 40(6): 745-50 0284-186X
•
Regular intake of non-opioid analgesics is associated with an increased risk of restless legs syndrome in patients maintained on antidepressants. Author(s): The Practice Rotmaintal for the Treatment of Affective and Anxiety Disorders, Heinersreuth, Germany.
[email protected] Source: Leutgeb, U Martus, P Eur-J-Med-Res. 2002 August 30; 7(8): 368-78 0949-2321
•
Regulation of 5-hydroxytryptamine1A receptor function in rat hippocampus by shortand long-term administration of 5-hydroxytryptamine1A agonist and antidepressants. Author(s): Ya'acov Herzog Center for Brain and Psychiatry Research, Ezrath Nashim Hospital, Jerusalem, Israel.
Nutrition
87
Source: Newman, M E Shapira, B Lerer, B J-Pharmacol-Exp-Ther. 1992 January; 260(1): 16-20 0022-3565 •
Repeated administration of antidepressants enhances agonist affinity for mesolimbic D2-receptors. Author(s): Institute of Pharmacology, Polish Academy of Science, Krakow. Source: Klimek, V Maj, J J-Pharm-Pharmacol. 1989 August; 41(8): 555-8 0022-3573
•
Repeated treatment with antidepressants does not modify the locomotor effect of dopaminergic stimulants injected into the rat hippocampus. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow. Source: Przegalinski, E Jurkowska, T Arch-Int-Pharmacodyn-Ther. 1990 May-June; 305152-62 0003-9780
•
The effect of antidepressants on rat aggressive behavior in the electric footshock and apomorphine-induced aggressiveness paradigms. Author(s): Department of Pharmacology, University of Tartu, Estonia.
[email protected] Source: Matto, V Skrebuhhova, T Allikmets, L Methods-Find-Exp-Clin-Pharmacol. 1998 May; 20(4): 329-37 0379-0355
•
The effect of antidepressants on serum melatonin levels in endogenous depression. Author(s): Department of Psychiatry, Himalayan Institute of Medical Sciences, Jolly Grant, Dehra Dun 248 140. Source: Varma, A Kaul, R K Varma, P Kalra, V Malhotra, V J-Assoc-Physicians-India. 2002 October; 50: 1262-5 0004-5772
•
The use of antidepressants among injecting drug users in Sydney, Australia. Author(s): National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia. Source: Darke, S Ross, J Addiction. 2000 March; 95(3): 407-17 0965-2140
•
The use of antidepressants in novel combination therapies. Author(s): Adult Psychiatry Division, Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN 37212-8646, USA.
[email protected] Source: Shelton, R C J-Clin-Psychiatry. 2003; 64 Suppl 2: 14-8 0160-6689
•
The utilization of antidepressants in community-dwelling and institutionalized elderly--results form a representative survey in Germany. Author(s): Department of Psychiatry, University of Leipzig, Germany.
[email protected] Source: Riedel Heller, S G Matschinger, H Schork, A Angermeyer, M C Pharmacopsychiatry. 2001 January; 34(1): 6-12 0176-3679
•
Treatment of depressions resistant to tricyclic antidepressants, related drugs or MAOinhibitors by lithium addition: review of the literature. Author(s): Psychiatrische Universitatsklinik Zurich, Switzerland. Source: Schopf, J Pharmacopsychiatry. 1989 September; 22(5): 174-82 0176-3679
•
Treatment of endogenous depressions resistant to tricyclic antidepressants or related drugs by lithium addition. Results of a placebo-controlled double-blind study. Author(s): Clinique psychiatrique universitaire, Hopital de Cery, Prilly-Lausanne, Switzerland. Source: Schopf, J Baumann, P Lemarchand, T Rey, M Pharmacopsychiatry. 1989 September; 22(5): 183-7 0176-3679
88
Antidepressants
•
Treatment of resistant depression. Review on the efficacy of various biological treatments, specifically in major depression resistant to cyclic antidepressants. Author(s): Department of Biological Psychiatry, Psychiatric Centre Bloemendaal, Hague, The Netherlands. Source: Nolen, W A Haffmans, J Int-Clin-Psychopharmacol. 1989 July; 4(3): 217-28 02681315
•
Tricyclic antidepressants block cholinergic nicotinic receptors and ATP secretion in bovine chromaffin cells. Author(s): Departamento de Farmacologia and Instituto de Neurociencias, Universidad Miguel Hernandez, Campus de San Juan, Alicante, Spain. Source: Izaguirre, V Fernandez Fernandez, J M Cena, V Gonzalez Garcia, C FEBS-Lett. 1997 November 24; 418(1-2): 39-42 0014-5793
•
Triiodothyronine augmentation for the treatment of depression in substance misusers unresponsive to tricyclic antidepressants. Author(s): Department of Psychiatry, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. Source: Kan, C K Ho, T P Hong-Kong-Med-J. 2001 September; 7(3): 299-302 1024-2708
The following information is typical of that found when using the “Full IBIDS Database” to search for “antidepressants” (or a synonym): •
A comparative analysis of standard and alternative antidepressants in the treatment of human immunodeficiency virus patients. Author(s): New York State Psychiatric Institue, NY 10032, USA. Source: Wagner, G J Rabkin, J G Rabkin, R Compr-Psychiatry. 1996 Nov-December; 37(6): 402-8 0010-440X
•
A double blind, randomized clinical trial assessing the efficacy and safety of augmenting standard antidepressant therapy with nimodipine in the treatment of 'vascular depression'. Author(s): Geriatric Neuropsychiatry Group, CEMIC University, Buenos Aires, Argentina. Source: Taragano, F E Allegri, R Vicario, A Bagnatti, P Lyketsos, C G Int-J-GeriatrPsychiatry. 2001 March; 16(3): 254-60 0885-6230
•
An open study of triiodothyronine augmentation of tricyclic antidepressants in inpatients with refractory depression. Author(s): Department of Biological Psychiatry, Psychiatric Centre Bloemendaal, The Hague, The Netherlands. Source: Birkenhager, T K Vegt, M Nolen, W A Pharmacopsychiatry. 1997 January; 30(1): 23-6 0176-3679
•
Antagonism by tricyclic antidepressants of the muscarinic receptors located on the adrenergic nerve endings in rabbit heart atrium. Author(s): Western Psychiatric Institute and Clinic, University of Pittsburgh, Pennsylvania. Source: Somogyi, G T Perel, J M J-Pharmacol-Exp-Ther. 1989 December; 251(3): 922-8 0022-3565
•
Antidepressant activity of S-adenosyl-L-methionine in mice and rats. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow. Source: Czyrak, A Rogoz, Z Skuza, G Zajaczkowski, W Maj, J J-Basic-Clin-PhysiolPharmacol. 1992 Jan-March; 3(1): 1-17 0792-6855
Nutrition
89
•
Antidepressant drug therapy: associated risks. Author(s): Department of PKF/TN, F. Hoffmann-La Roche & Co., Ltd., Basle, Switzerland. Source: Amrein, R Allen, S R Vranesic, D Stabl, M J-Neural-Transm-Suppl. 1988; 2673-86 0303-6995
•
Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction. Author(s): Department of Pharmacology, Imperial College School of Medicine, P.O. Box 8751, London W13 8WH, UK.
[email protected] Source: Montgomery, S A Baldwin, D S Riley, A J-Affect-Disord. 2002 May; 69(1-3): 11940 0165-0327
•
Antidepressants and thyroid hormone levels. Author(s): Mood Disorders Program, Clarke Institute of Psychiatry, Toronto, Ontario, Canada. Source: Joffe, R T Singer, W Acta-Med-Austriaca. 1992; 19 Suppl 196-7 0303-8173
•
Antidepressants given repeatedly increase the behavioural effect of dopamine D-2 agonist. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. Source: Maj, J Rogoz, Z Skuza, G Sowinska, H J-Neural-Transm-Gen-Sect. 1989; 78(1): 18 0300-9564
•
Antidepressants in cancer pain. Author(s): Department of Pharmacology, School of Medicine, University of Milan, Italy. Source: Panerai, A E Bianchi, M Sacerdote, P Ripamonti, C Ventafridda, V De Conno, F J-Palliat-Care. 1991 Winter; 7(4): 42-4 0825-8597
•
Association of antidepressants and other medications with mortality in the residential-care elderly. Author(s): Department of Psychiatry, University of Pennsylvania, Philadelphia Geriatric Center 19104. Source: Katz, I R Parmelee, P A Beaston Wimmer, P Smith, B D J-Geriatr-PsychiatryNeurol. 1994 Oct-December; 7(4): 221-6 0891-9887
•
Differential effects of clonidine, lithium and quinine in the forced swimming test in mice for antidepressants: possible roles of serotoninergic systems. Author(s): GIS Medicament, Department of Pharmacology, Faculty of Medicine, Nantes, France. Source: Bourin, M Hascoet, M Colombel, M C Redrobe, J P Baker, G B EurNeuropsychopharmacol. 1996 August; 6(3): 231-6 0924-977X
•
Differential regulation of neuropeptide Y mRNA expression in the arcuate nucleus and locus coeruleus by stress and antidepressants. Author(s): Clinical Neuroendocrinology Branch; Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1284, USA. Source: Makino, S Baker, R A Smith, M A Gold, P W J-Neuroendocrinol. 2000 May; 12(5): 387-95 0953-8194
•
Direct influence of antidepressants on GTP binding protein of adenylate cyclase in cell membranes of the cerebral cortex of rats. Author(s): Department of Neuropsychiatry, Fujita-Gakuen Health University, School of Medicine, Aichi, Japan. Source: Yamaoka, K Nanba, T Nomura, S J-Neural-Transm. 1988; 71(3): 165-75 0300-9564
90
Antidepressants
•
Does higher cardiovascular response to ECT predict early antidepressant effect? Author(s): Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, 560 India. Source: Saravanan, E S Gangadhar, B N Janakiramaiah, N Pandey, R S Murthy, H S Subbakrishna, D K J-Affect-Disord. 2002 May; 69(1-3): 101-8 0165-0327
•
Does sodium valproate increase clinical effects of antidepressants? Author(s): Inst. Organic Chemistry and Biochemistry, Czechosl. Acad. Sci., Prague. Source: Vinar, O Dvorak, A Obrovska, V Kriskova, M Turcek, K Act-Nerv-Super(Praha). 1989 June; 31(2): 103-5 0001-7604
•
Effects of antidepressants on thyroid stimulating hormone release in rats under ether stress. Author(s): Department of Psychiatry, Kobe University Medical School, Japan. Source: Kadono, Y Kaneda, H Maeda, K Psychiatry-Clin-Neurosci. 1995 August; 49(4): 231-6 1323-1316
•
Effects of chronic antidepressant treatment on alpha 1- and alpha 2-adrenoceptors in the rat anococcygeus muscle. Author(s): Department de Farmacologia i Psiquiatria, Universitat Autonoma de Barcelona, Bellaterra, Spain. Source: Vila, E Salles, J Badia, A J-Neural-Transm-Gen-Sect. 1990; 82(3): 205-12 0300-9564
•
Effects of chronic treatment with lithium and antidepressants on [3H]forskolin binding to rat cerebral cortical membranes. Author(s): Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo. Source: Odagaki, Y Koyama, T Yamashita, I Jpn-J-Psychiatry-Neurol. 1991 March; 45(1): 125-6 0912-2036
•
Effects of subchronic administration of antidepressants and anxiolytics on levels of the alpha subunits of G proteins in the rat brain. Author(s): Department of Psychiatry, College of Medicine, University of Illinois at Chicago, USA. Source: Dwivedi, Y Pandey, G N J-Neural-Transm. 1997; 104(6-7): 747-60
•
Hypericum perforatum extracts as potential antidepressants. Author(s): National Institute of Mental Health, Bethesda, MD, USA.
[email protected] Source: Vitiello, B J-Pharm-Pharmacol. 1999 May; 51(5): 513-7 0022-3573
•
Influence of antidepressant drugs on seizure susceptibility and the anticonvulsant activity of valproate in mice. Author(s): Department of Pharmacology, Medical School, Lublin, Poland. Source: Kleinrok, Z Gustaw, J Czuczwar, S J J-Neural-Transm-Suppl. 1991; 3485-90 03036995
•
Influence of changes in protein binding on the central activity of antidepressants. Author(s): Department of Pharmacology, Faculty of Medicine, Basque Country, Leioa, Vizcaya, Spain. Source: Torres, I Gomez, E Garcia, E Suarez, E Rodriguez Sasiain, J M Calvo, R J-PharmPharmacol. 1992 June; 44(6): 531-3 0022-3573
•
Influence of food intake on the bioavailability of zimeldine and its active metabolite, norzimeldine [Antidepressants]. Source: Wahlen, A. Westerlund, D. Wahlin Boll, E. Melander, A. Drug-Nutr-Interact. New York : Alan R. Liss. 1983. volume 2 (3) page 175-181. 0272-3530
Nutrition
91
•
Inhibition of acid secretion in guinea pigs by tricyclic antidepressants: comparison with ranitidine and omeprazole. Author(s): Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Source: Batzri, S Brugada, O Harmon, J W Rich, N M J-Pharmacol-Exp-Ther. 1988 August; 246(2): 493-9 0022-3565
•
Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo. Author(s): Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts. Source: von Moltke, L L Greenblatt, D J Cotreau Bibbo, M M Duan, S X Harmatz, J S Shader, R I J-Pharmacol-Exp-Ther. 1994 March; 268(3): 1278-83 0022-3565
•
Inhibitory effects of antidepressants on NMDA-induced currents in Xenopus oocytes injected with rat brain RNA. Author(s): Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. Source: Tohda, M Urushihara, H Nomura, Y Neurochem-Int. 1995 January; 26(1): 53-8 0197-0186
•
Involvement of metabolites in the inhibitory effects of 2-(4-ethyl-1-piperazinyl)-4phenylquinoline dimaleate (AD-2646), a new quinoline derivative, on gastric acid secretion. A comparison with tricyclic antidepressants. Author(s): Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan. Source: Kimura, Y Yano, S Watanabe, K J-Pharmacobiodyn. 1989 January; 12(1): 43-9 0386-846X
•
Involvement of protein kinase in the regulation of beta-adrenergic receptors by antidepressants. Author(s): Department of Neuropsychiatry, St. Marianna University School of Medicine, Kanagawa, Japan. Source: Asakura, M Tsukamoto, T Kubota, H Osada, K Imafuku, J Nishizaki, J Sato, A Nakanishi, J Shimbo, K Shibata, M et al. Int-J-Clin-Pharmacol-Res. 1989; 9(2): 123-30 0251-1649
•
Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late-life depression. Author(s): University Department of Old Age Psychiatry, Manchester Royal Infirmary. Source: Simpson, S Baldwin, R C Jackson, A Burns, A S Psychol-Med. 1998 September; 28(5): 1015-26 0033-2917
•
Isoniazid and antidepressants: is there cause for concern? Author(s): Fairfield Infectious Diseases Hospital, Australia. Source: Judd, F K Mijch, A M Cockram, A Norman, T R Int-Clin-Psychopharmacol. 1994 Summer; 9(2): 123-5 0268-1315
•
Liability in prescribing choice: the example of the antidepressants. Author(s): Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Australia. Source: Beerworth, E E Tiller, J W Aust-N-Z-J-Psychiatry. 1998 August; 32(4): 560-6 00048674
92
Antidepressants
•
Lithium addition in endogenous depressions resistant to tricyclic antidepressants or related drugs: relation to the status of the pituitary-thyroid axis. Author(s): Psychiatric University Hospital, Zurich, Switzerland. Source: Schopf, J Lemarchand, T Pharmacopsychiatry. 1994 September; 27(5): 198-201 0176-3679
•
Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity. Author(s): Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Skovagervej 2, DK-8240 Risskov, Denmark.
[email protected] Source: Wegener, G Volke, V Harvey, B H Rosenberg, R Brain-Res. 2003 January 3; 959(1): 128-34 0006-8993
•
No alterations in the 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase activity in the hippocampal membranes from rats chronically treated with lithium or antidepressants. Author(s): Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan. Source: Odagaki, Y Koyama, T Yamashita, I J-Neural-Transm-Gen-Sect. 1991; 86(2): 8596 0300-9564
•
Once daily sustained release tablets of venlafaxine, a novel antidepressant. Author(s): Pharmaceutical Division, Department of Chemical Technology (Autonomous), University of Mumbai, Nathalal Parikh Marg, Matunga, Mumbai400019, India. Source: Makhija, S N Vavia, P R Eur-J-Pharm-Biopharm. 2002 July; 54(1): 9-15 0939-6411
•
Pharmacokinetic patterns of repeated administration of antidepressants in animals. I. Implications for antinociceptive action of clomipramine in mice. Author(s): Laboratoire de Pharmacologie Medicale, INSERM U195, Faculte de Medecine, Clermont-Ferrand, France. Source: Eschalier, A Fialip, J Varoquaux, O Makambila, M C Marty, H Bastide, P JPharmacol-Exp-Ther. 1988 June; 245(3): 963-8 0022-3565
•
Pharmacological effects of milnacipran, a new antidepressant, given repeatedly on the alpha1-adrenergic and serotonergic 5-HT2A systems. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow. Source: Maj, J Rogoz, Z Dlaboga, D Dziedzicka Wasylewska, M J-Neural-Transm. 2000; 107(11): 1345-59
•
Plasma level of lithium in rats treated subchronically with lithium and tricyclic antidepressants. Author(s): P. Z. Dept. of Pharmacology and Toxicol., Faculty of Pharmacy, Charles Univ., Hradec Kralove, CSSR. Source: Zackova, P Krpalek, P Jaros, P Hajkova, L Act-Nerv-Super-(Praha). 1989 December; 31(4): 277-9 0001-7604
•
Randomized trial of opioids versus tricyclic antidepressants for radiation-induced mucositis pain in head and neck cancer. Author(s): Department of Oncology, Aarhus University Hospital, Denmark.
[email protected] Source: Ehrnrooth, E Grau, C Zachariae, R Andersen, J Acta-Oncol. 2001; 40(6): 745-50 0284-186X
Nutrition
93
•
Regular intake of non-opioid analgesics is associated with an increased risk of restless legs syndrome in patients maintained on antidepressants. Author(s): The Practice Rotmaintal for the Treatment of Affective and Anxiety Disorders, Heinersreuth, Germany.
[email protected] Source: Leutgeb, U Martus, P Eur-J-Med-Res. 2002 August 30; 7(8): 368-78 0949-2321
•
Regulation of 5-hydroxytryptamine1A receptor function in rat hippocampus by shortand long-term administration of 5-hydroxytryptamine1A agonist and antidepressants. Author(s): Ya'acov Herzog Center for Brain and Psychiatry Research, Ezrath Nashim Hospital, Jerusalem, Israel. Source: Newman, M E Shapira, B Lerer, B J-Pharmacol-Exp-Ther. 1992 January; 260(1): 16-20 0022-3565
•
Repeated administration of antidepressants enhances agonist affinity for mesolimbic D2-receptors. Author(s): Institute of Pharmacology, Polish Academy of Science, Krakow. Source: Klimek, V Maj, J J-Pharm-Pharmacol. 1989 August; 41(8): 555-8 0022-3573
•
Repeated treatment with antidepressants does not modify the locomotor effect of dopaminergic stimulants injected into the rat hippocampus. Author(s): Institute of Pharmacology, Polish Academy of Sciences, Krakow. Source: Przegalinski, E Jurkowska, T Arch-Int-Pharmacodyn-Ther. 1990 May-June; 305152-62 0003-9780
•
The effect of antidepressants on rat aggressive behavior in the electric footshock and apomorphine-induced aggressiveness paradigms. Author(s): Department of Pharmacology, University of Tartu, Estonia.
[email protected] Source: Matto, V Skrebuhhova, T Allikmets, L Methods-Find-Exp-Clin-Pharmacol. 1998 May; 20(4): 329-37 0379-0355
•
The use of antidepressants among injecting drug users in Sydney, Australia. Author(s): National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia. Source: Darke, S Ross, J Addiction. 2000 March; 95(3): 407-17 0965-2140
•
The utilization of antidepressants in community-dwelling and institutionalized elderly--results form a representative survey in Germany. Author(s): Department of Psychiatry, University of Leipzig, Germany.
[email protected] Source: Riedel Heller, S G Matschinger, H Schork, A Angermeyer, M C Pharmacopsychiatry. 2001 January; 34(1): 6-12 0176-3679
•
Treatment of depressions resistant to tricyclic antidepressants, related drugs or MAOinhibitors by lithium addition: review of the literature. Author(s): Psychiatrische Universitatsklinik Zurich, Switzerland. Source: Schopf, J Pharmacopsychiatry. 1989 September; 22(5): 174-82 0176-3679
•
Treatment of endogenous depressions resistant to tricyclic antidepressants or related drugs by lithium addition. Results of a placebo-controlled double-blind study. Author(s): Clinique psychiatrique universitaire, Hopital de Cery, Prilly-Lausanne, Switzerland. Source: Schopf, J Baumann, P Lemarchand, T Rey, M Pharmacopsychiatry. 1989 September; 22(5): 183-7 0176-3679
94
Antidepressants
•
Treatment of resistant depression. Review on the efficacy of various biological treatments, specifically in major depression resistant to cyclic antidepressants. Author(s): Department of Biological Psychiatry, Psychiatric Centre Bloemendaal, Hague, The Netherlands. Source: Nolen, W A Haffmans, J Int-Clin-Psychopharmacol. 1989 July; 4(3): 217-28 02681315
•
Tricyclic antidepressants block cholinergic nicotinic receptors and ATP secretion in bovine chromaffin cells. Author(s): Departamento de Farmacologia and Instituto de Neurociencias, Universidad Miguel Hernandez, Campus de San Juan, Alicante, Spain. Source: Izaguirre, V Fernandez Fernandez, J M Cena, V Gonzalez Garcia, C FEBS-Lett. 1997 November 24; 418(1-2): 39-42 0014-5793
•
Triiodothyronine augmentation for the treatment of depression in substance misusers unresponsive to tricyclic antidepressants. Author(s): Department of Psychiatry, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. Source: Kan, C K Ho, T P Hong-Kong-Med-J. 2001 September; 7(3): 299-302 1024-2708
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
•
The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
•
The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
•
The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
•
The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
•
Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
•
Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
•
Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Nutrition
95
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
•
Google: http://directory.google.com/Top/Health/Nutrition/
•
Healthnotes: http://www.healthnotes.com/
•
Open Directory Project: http://dmoz.org/Health/Nutrition/
•
Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
•
WebMDHealth: http://my.webmd.com/nutrition
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to antidepressants; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Folic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,887,00.html Pantothenic Acid Source: Healthnotes, Inc.; www.healthnotes.com Pyridoxine Alternative names: Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com Riboflavin Alternative names: Vitamin B2 (Riboflavin) Source: Integrative Medicine Communications; www.drkoop.com Thiamine Alternative names: Vitamin B1 (Thiamine) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin B1 Source: Healthnotes, Inc.; www.healthnotes.com
96
Antidepressants
Vitamin B1 (thiamine) Alternative names: Thiamine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B2 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B2 (riboflavin) Alternative names: Riboflavin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B6 (pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com •
Minerals Fluoxetine Source: Healthnotes, Inc.; www.healthnotes.com Paroxetine Source: Healthnotes, Inc.; www.healthnotes.com
•
Food and Diet Nutritional Yeast Alternative names: Brewer's Yeast Source: Integrative Medicine Communications; www.drkoop.com Tyramine-free Diet Source: Healthnotes, Inc.; www.healthnotes.com
97
CHAPTER 3. ALTERNATIVE ANTIDEPRESSANTS
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to antidepressants. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “antidepressants” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Combining Supplements and Prescription Drugs: What Your Patients Need to Know Source: Alternative and Complementary Therapies. 6(4): 177-183. August 2000. Summary: This journal article reviews what patients need to know about combining herbal supplements and prescription drugs. First, it looks at general clinical issues regarding the concomitant use of herbs and drugs. Then, it summarizes the major concerns, including the lack of knowledge about herbs, lack of quality control for herbal supplements, lack of patient communication about the use of botanicals, and lack of practitioner knowledge about potential interactions. Finally, it reviews known interactions between popular herbal supplements and commonly prescribed classes of drugs, including immunostimulant and immunosuppressive drugs, antidepressants, monoamine oxidase inhibitors, antibiotics, anticoagulants, antihypertensives and diuretics, hypoglycemics and hyperglycemics, and sedatives. The article includes a list
98
Antidepressants
of herb-drug combinations to avoid, a resources list, a summary of advice for patients, a recommended reading list, and 21 references.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to antidepressants and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “antidepressants” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to antidepressants: •
A patient with Cotard syndrome who showed an improvement in single photon emission computed tomography findings after successful treatment with antidepressants. Author(s): Hashioka S, Monji A, Sasaki M, Yoshida I, Baba K, Tashiro N. Source: Clinical Neuropharmacology. 2002 September-October; 25(5): 276-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410062&dopt=Abstract
•
A placebo-controlled, double-blind trial of Ginkgo biloba for antidepressant-induced sexual dysfunction. Author(s): Kang BJ, Lee SJ, Kim MD, Cho MJ. Source: Human Psychopharmacology. 2002 August; 17(6): 279-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404672&dopt=Abstract
•
A study of the antidepressant activity of Hypericum perforatum on animal models. Author(s): Gambarana C, Tolu PL, Masi F, Rinaldi M, Giachetti D, Morazzoni P, De Montis MG. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S42-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518074&dopt=Abstract
•
Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity. Author(s): Jensen AG, Hansen SH, Nielsen EO. Source: Life Sciences. 2001 February 23; 68(14): 1593-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263672&dopt=Abstract
•
Adverse neuropsychiatric reactions to herbal and over-the-counter “antidepressants”. Author(s): Pies R. Source: The Journal of Clinical Psychiatry. 2000 November; 61(11): 815-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105733&dopt=Abstract
Alternative Medicine 99
•
Adverse pulmonary vascular effects of high dose tricyclic antidepressants: acute and chronic animal studies. Author(s): Liu X, Emery CJ, Laude E, Herget J, Gill G, Cope G, Barer GR. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 August; 20(2): 344-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212966&dopt=Abstract
•
Antidepressant activity of aqueous extracts of Curcuma longa in mice. Author(s): Yu ZF, Kong LD, Chen Y. Source: Journal of Ethnopharmacology. 2002 November; 83(1-2): 161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413724&dopt=Abstract
•
Antidepressant activity of hyperforin conjugates of the St. John's wort, Hypericum perforatum Linn.: an experimental study. Author(s): Muruganandam AV, Bhattacharya SK, Ghosal S. Source: Indian J Exp Biol. 2001 December; 39(12): 1302-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018529&dopt=Abstract
•
Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats. Author(s): Sairam K, Dorababu M, Goel RK, Bhattacharya SK. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 April; 9(3): 207-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046860&dopt=Abstract
•
Antidepressant effects of apocynum venetum leaves in a forced swimming test. Author(s): Butterweck V, Nishibe S, Sasaki T, Uchida M. Source: Biological & Pharmaceutical Bulletin. 2001 July; 24(7): 848-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456130&dopt=Abstract
•
Antidepressant effects of Banxia Houpu decoction, a traditional Chinese medicinal empirical formula. Author(s): Luo L, Nong Wang J, Kong LD, Jiang QG, Tan RX. Source: Journal of Ethnopharmacology. 2000 November; 73(1-2): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11025166&dopt=Abstract
•
Antidepressant effects of the herb Salvia divinorum: a case report. Author(s): Hanes KR. Source: Journal of Clinical Psychopharmacology. 2001 December; 21(6): 634-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763023&dopt=Abstract
100 Antidepressants
•
Antidepressant effects of the methanol extract of several Hypericum species from the Canary Islands. Author(s): Sanchez-Mateo CC, Prado B, Rabanal RM. Source: Journal of Ethnopharmacology. 2002 January; 79(1): 119-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744305&dopt=Abstract
•
Antidepressant trials generally have methodological defects. Author(s): Even C, Friedman S, Dardennes R. Source: Bmj (Clinical Research Ed.). 2001 September 8; 323(7312): 574. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573492&dopt=Abstract
•
Antidepressants for smoking cessation: a promising new approach? Author(s): Huibers MJ, Chavannes NH, Wagena EJ, van Schayck CP. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 September; 16(3): 379-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11028646&dopt=Abstract
•
Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Author(s): Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2000 December; 7(6): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194174&dopt=Abstract
•
Clinical features of antidepressant associated manic and hypomanic switches in bipolar disorder. Author(s): Serretti A, Artioli P, Zanardi R, Rossini D. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 August; 27(5): 751-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921905&dopt=Abstract
•
Clinical trials with hypericum extracts in patients with depression--results, comparisons, conclusions for therapy with antidepressant drugs. Author(s): Schulz V. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 July; 9(5): 468-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222670&dopt=Abstract
•
Cluster analysis of symptoms during antidepressant treatment with Hypericum extract in mildly to moderately depressed out-patients. A meta-analysis of data from three randomized, placebo-controlled trials. Author(s): Kasper S, Dienel A.
Alternative Medicine 101
Source: Psychopharmacology. 2002 November; 164(3): 301-8. Epub 2002 September 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424554&dopt=Abstract •
Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Author(s): Altshuler LL, Bauer M, Frye MA, Gitlin MJ, Mintz J, Szuba MP, Leight KL, Whybrow PC. Source: The American Journal of Psychiatry. 2001 October; 158(10): 1617-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578993&dopt=Abstract
•
Effects of antidepressant pharmacotherapy after repetitive transcranial magnetic stimulation in major depression: an open follow-up study. Author(s): Schule C, Zwanzger P, Baghai T, Mikhaiel P, Thoma H, Moller HJ, Rupprecht R, Padberg F. Source: Journal of Psychiatric Research. 2003 March-April; 37(2): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842168&dopt=Abstract
•
Effects of Hypericum perforatum (St. John's wort) on passive avoidance in the rat: evaluation of potential neurochemical mechanisms underlying its antidepressant activity. Author(s): Misane I, Ogren SO. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S89-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518084&dopt=Abstract
•
Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Author(s): Drevets WC, Bogers W, Raichle ME. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2002 December; 12(6): 527-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468016&dopt=Abstract
•
Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment outcome in geriatric depression. Author(s): Smith GS, Reynolds CF 3rd, Houck PR, Dew MA, Ma Y, Mulsant BH, Pollock BG. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2002 September-October; 10(5): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213690&dopt=Abstract
•
How coil-cortex distance relates to age, motor threshold, and antidepressant response to repetitive transcranial magnetic stimulation. Author(s): Kozel FA, Nahas Z, deBrux C, Molloy M, Lorberbaum JP, Bohning D, Risch SC, George MS.
102 Antidepressants
Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2000 Summer; 12(3): 376-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10956572&dopt=Abstract •
Hyperforin--antidepressant activity by a novel mechanism of action. Author(s): Muller WE, Singer A, Wonnemann M. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S98-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518085&dopt=Abstract
•
Interleukin-6 involvement in antidepressant action of Hypericum perforatum. Author(s): Calapai G, Crupi A, Firenzuoli F, Inferrera G, Ciliberto G, Parisi A, De Sarro G, Caputi AP. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S8-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518082&dopt=Abstract
•
Involvement of monoaminergic system in the antidepressant-like effect of the hydroalcoholic extract of Siphocampylus verticillatus. Author(s): Rodrigues AL, da Silva GL, Mateussi AS, Fernandes ES, Miguel OG, Yunes RA, Calixto JB, Santos AR. Source: Life Sciences. 2002 February 8; 70(12): 1347-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885577&dopt=Abstract
•
Is there a role for hemoperfusion/hemodialysis as a treatment option in severe tricyclic antidepressant intoxication? Author(s): Frank RD, Kierdorf HP. Source: Int J Artif Organs. 2000 September; 23(9): 618-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11059884&dopt=Abstract
•
Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial. Author(s): Holroyd KA, O'Donnell FJ, Stensland M, Lipchik GL, Cordingley GE, Carlson BW. Source: Jama : the Journal of the American Medical Association. 2001 May 2; 285(17): 2208-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11325322&dopt=Abstract
•
Mimosa pudica may possess antidepressant actions in the rat. Author(s): Molina M, Contreras CM, Tellez-Alcantara P. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 1999 November; 6(5): 319-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11962537&dopt=Abstract
Alternative Medicine 103
•
Mood-enhancing antidepressant St. John's wort inhibits the activation of human immunodeficiency virus gene expression by ultraviolet light. Author(s): Taher MM, Lammering GM, Hershey CM, Valerie KC. Source: Iubmb Life. 2002 December; 54(6): 357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665247&dopt=Abstract
•
Pharmacological study on antidepressant activity of 50% ethanol extract of a formulated ayurvedic product in rats. Author(s): Bopaiah CP, Pradhan N, Venkataram BS. Source: Journal of Ethnopharmacology. 2000 October; 72(3): 411-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10996280&dopt=Abstract
•
Regional cerebral blood flow in mood disorders, V.: Effects of antidepressant medication in late-life depression. Author(s): Nobler MS, Roose SP, Prohovnik I, Moeller JR, Louie J, Van Heertum RL, Sackeim HA. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2000 Fall; 8(4): 289-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069268&dopt=Abstract
•
Researching the antidepressant actions of Hypericum perforatum (St. John's wort) in animals and man. Author(s): Franklin M, Cowen PJ. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S29-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518072&dopt=Abstract
•
Role of hyperforin in the antidepressant-like activity of Hypericum perforatum extracts. Author(s): Cervo L, Rozio M, Ekalle-Soppo CB, Guiso G, Morazzoni P, Caccia S. Source: Psychopharmacology. 2002 December; 164(4): 423-8. Epub 2002 September 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457273&dopt=Abstract
•
Rutin is essential for the antidepressant activity of Hypericum perforatum extracts in the forced swimming test. Author(s): Noldner M, Schotz K. Source: Planta Medica. 2002 July; 68(7): 577-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142988&dopt=Abstract
•
Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum. Author(s): Calapai G, Crupi A, Firenzuoli F, Inferrera G, Squadrito F, Parisi A, De Sarro G, Caputi A.
104 Antidepressants
Source: Pharmacopsychiatry. 2001 March; 34(2): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302563&dopt=Abstract •
Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation. Author(s): Eichhammer P, Kharraz A, Wiegand R, Langguth B, Frick U, Aigner JM, Hajak G. Source: Life Sciences. 2002 March 1; 70(15): 1741-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002519&dopt=Abstract
•
St John's wort, a herbal antidepressant, activates the steroid X receptor. Author(s): Wentworth JM, Agostini M, Love J, Schwabe JW, Chatterjee VK. Source: The Journal of Endocrinology. 2000 September; 166(3): R11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10974665&dopt=Abstract
•
Structural and energetic processes related to P300: LORETA findings in depression and effects of antidepressant drugs. Author(s): Anderer P, Saletu B, Semlitsch HV, Pascual-Marqui RD. Source: Methods Find Exp Clin Pharmacol. 2002; 24 Suppl D: 85-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575474&dopt=Abstract
•
Subjective effects of antidepressants: a pilot study of the varieties of antidepressantinduced experiences in meditators. Author(s): Bitner R, Hillman L, Victor B, Walsh R. Source: The Journal of Nervous and Mental Disease. 2003 October; 191(10): 660-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14555868&dopt=Abstract
•
The utilization of antidepressants in community-dwelling and institutionalized elderly--results form a representative survey in Germany. Author(s): Riedel-Heller SG, Matschinger H, Schork A, Angermeyer MC. Source: Pharmacopsychiatry. 2001 January; 34(1): 6-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229623&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
•
AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
•
Chinese Medicine: http://www.newcenturynutrition.com/
•
drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
Alternative Medicine 105
•
Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
•
Google: http://directory.google.com/Top/Health/Alternative/
•
Healthnotes: http://www.healthnotes.com/
•
MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
•
Open Directory Project: http://dmoz.org/Health/Alternative/
•
HealthGate: http://www.tnp.com/
•
WebMDHealth: http://my.webmd.com/drugs_and_herbs
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
•
Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to antidepressants; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Anxiety Source: Healthnotes, Inc.; www.healthnotes.com Anxiety Source: Integrative Medicine Communications; www.drkoop.com Anxiety and Panic Attacks Source: Prima Communications, Inc.www.personalhealthzone.com Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Attention Deficit Disorder Source: Prima Communications, Inc.www.personalhealthzone.com Attention Deficit Hyperactivity Disorder Source: Integrative Medicine Communications; www.drkoop.com Autism Source: Healthnotes, Inc.; www.healthnotes.com Bipolar Disorder Source: Healthnotes, Inc.; www.healthnotes.com
106 Antidepressants
Bladder Infection Alternative names: Urinary Tract Infection [UTI] Source: Prima Communications, Inc.www.personalhealthzone.com Bulimia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Chronic Fatigue Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Chronic Fatigue Syndrome Source: Integrative Medicine Communications; www.drkoop.com Chronic Obstructive Pulmonary Disease Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Healthnotes, Inc.; www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com Depression (mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Eating Disorders Source: Healthnotes, Inc.; www.healthnotes.com Emphysema Source: Integrative Medicine Communications; www.drkoop.com Erectile Dysfunction Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Gastroesophageal Reflux Disease Source: Integrative Medicine Communications; www.drkoop.com Heartburn Source: Integrative Medicine Communications; www.drkoop.com Heat Exhaustion Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 107
Hives Source: Healthnotes, Inc.; www.healthnotes.com Impotence Source: Prima Communications, Inc.www.personalhealthzone.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Prima Communications, Inc.www.personalhealthzone.com Irritable Bowel Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headaches Source: Prima Communications, Inc.www.personalhealthzone.com Multiple Sclerosis Source: Healthnotes, Inc.; www.healthnotes.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Prima Communications, Inc.www.personalhealthzone.com Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com Pms Source: Integrative Medicine Communications; www.drkoop.com Pms Alternative names: Premenstrual Stress Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Post Traumatic Stress Disorder Source: Integrative Medicine Communications; www.drkoop.com Premenstrual Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Premenstrual Syndrome Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com
108 Antidepressants
Ptsd Source: Integrative Medicine Communications; www.drkoop.com Seasonal Affective Disorder Source: Healthnotes, Inc.; www.healthnotes.com Sexual Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Stress Source: Integrative Medicine Communications; www.drkoop.com Temporomandibular Joint Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Tmj Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements 5-htp Alternative names: 5-Hydroxytryptophan (5-HTP) Source: Integrative Medicine Communications; www.drkoop.com 5-htp (5-hydroxytryptophan) Source: Prima Communications, Inc.www.personalhealthzone.com 5-hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com 5-hydroxytryptophan (5-htp) Alternative names: 5-HTP Source: Integrative Medicine Communications; www.drkoop.com American Ginseng Alternative names: Ginseng, American Source: Integrative Medicine Communications; www.drkoop.com Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com Asian Ginseng Alternative names: Ginseng, Asian Source: Integrative Medicine Communications; www.drkoop.com Brewer's Yeast Alternative names: Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 109
Bupropion Source: Healthnotes, Inc.; www.healthnotes.com Citalopram Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Alternative names: CoQ10 Source: Integrative Medicine Communications; www.drkoop.com Coenzyme Q10 (coq10) Source: Prima Communications, Inc.www.personalhealthzone.com Coq10 Alternative names: Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com Cranberry Source: Prima Communications, Inc.www.personalhealthzone.com Ephedra Alternative names: Ephedra sinica, Ephedra intermedia, Ephedra equisetina Source: Healthnotes, Inc.; www.healthnotes.com Ephedra Alternative names: Ephedra sinensis Source: Integrative Medicine Communications; www.drkoop.com Ephedra Sinensis Source: Integrative Medicine Communications; www.drkoop.com Fiber Source: Integrative Medicine Communications; www.drkoop.com Fluvoxamine Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Biloba Alternative names: Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Haloperidol Source: Healthnotes, Inc.; www.healthnotes.com
110 Antidepressants
Hypericum Perforatum Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com Indian Tobacco Source: Integrative Medicine Communications; www.drkoop.com Kava Alternative names: Piper methysticum Source: Healthnotes, Inc.; www.healthnotes.com Kava Source: Prima Communications, Inc.www.personalhealthzone.com Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Klamathweed Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com Lithium Source: Healthnotes, Inc.; www.healthnotes.com Lobelia Alternative names: Lobelia inflata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lobelia Alternative names: Lobelia inflata, Indian Tobacco Source: Integrative Medicine Communications; www.drkoop.com Lobelia Inflata Source: Integrative Medicine Communications; www.drkoop.com Ma Huang Alternative names: Ephedra Source: Integrative Medicine Communications; www.drkoop.com Maidenhair Tree Alternative names: Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com Mao Inhibitors Source: Prima Communications, Inc.www.personalhealthzone.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 111
Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Mirtazapine Source: Healthnotes, Inc.; www.healthnotes.com Nefazodone Source: Healthnotes, Inc.; www.healthnotes.com Panax Ginseng Alternative names: Asian Ginseng Source: Integrative Medicine Communications; www.drkoop.com Panax Quinquefolium Alternative names: American Ginseng Source: Integrative Medicine Communications; www.drkoop.com Passion Flower Alternative names: Passiflora incarnata Source: Healthnotes, Inc.; www.healthnotes.com Phenelzine Source: Healthnotes, Inc.; www.healthnotes.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Piper Alternative names: Kava; Piper methysticum Forst.f Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org S-adenosylmethionine (same) Alternative names: SAMe Source: Integrative Medicine Communications; www.drkoop.com SAMe Alternative names: S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html Selective Serotonin Reuptake Inhibitors (ssris) Source: Integrative Medicine Communications; www.drkoop.com Selegiline Source: Healthnotes, Inc.; www.healthnotes.com
112 Antidepressants
Sertraline Source: Healthnotes, Inc.; www.healthnotes.com St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc.; www.healthnotes.com St. John's Wort Alternative names: Hypericum perforatum Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Trazodone Source: Healthnotes, Inc.; www.healthnotes.com Tricyclic Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com Tricyclic Antidepressants Source: Prima Communications, Inc.www.personalhealthzone.com Tricyclic Antidepressants (tcas) Source: Integrative Medicine Communications; www.drkoop.com Tyrosine Source: Integrative Medicine Communications; www.drkoop.com Venlafaxine Source: Healthnotes, Inc.; www.healthnotes.com Yohimbe Alternative names: Pausinystalia yohimbe Source: Healthnotes, Inc.; www.healthnotes.com Yohimbe Source: Prima Communications, Inc.www.personalhealthzone.com Yohimbe Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,830,00.html Zolpidem Source: Healthnotes, Inc.; www.healthnotes.com
Alternative Medicine 113
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
115
CHAPTER 4. DISSERTATIONS ON ANTIDEPRESSANTS Overview In this chapter, we will give you a bibliography on recent dissertations relating to antidepressants. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “antidepressants” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on antidepressants, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Antidepressants ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to antidepressants. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
CRE-binding Transcription Factors Mediate Distinct Effects of Antidepressant Drugs in the Brain by Conti, Alana Caroline; Phd from University of Pennsylvania, 2003, 133 pages http://wwwlib.umi.com/dissertations/fullcit/3087387
•
Evaluation of the Role of Central Beta-1 Adrenergic Receptors in the Mechanism of Action of Antidepressant Drugs by Crissman, Alicia Marie; Phd from The University of Tennessee Center for the Health Sciences, 2002, 123 pages http://wwwlib.umi.com/dissertations/fullcit/3067789
•
Interactions between Serotonergic and Noradrenergic Systems: Their Involvement in Antidepressant Treatment of Anxiety and Affective Disorders by Szabo, Steven T.; Phd from Mcgill University (canada), 2002, 507 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78780
116 Antidepressants
•
Pricing, Advertising and Entry in the Market for Antidepressant Drugs by Currie, Gillian Ruth, Phd from Yale University, 1998, 126 pages http://wwwlib.umi.com/dissertations/fullcit/9831417
•
The Role of Price in the Demand for Antidepressants by Domino, Marisa Elena, Phd from The Johns Hopkins University, 1998, 221 pages http://wwwlib.umi.com/dissertations/fullcit/9832864
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
117
CHAPTER 5. CLINICAL TRIALS AND ANTIDEPRESSANTS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning antidepressants.
Recent Trials on Antidepressants The following is a list of recent trials dedicated to antidepressants.8 Further information on a trial is available at the Web site indicated. •
An Investigation of the Antidepressant Efficacy of the 5-HT2A Antagonist, M100907 in Combination with Escitalopram in Treatment Resistant Depression Condition(s): Depressive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Major Affective Disorders are common and often chronic life threatening illnesses. Furthermore a significant fraction of patients do not respond to treatment with serotonin reuptake inhibitors (SSRI's), have only a partial response with continued significant morbidity and functional impairment, or suffer from drug induced side effects that decrease the individuals' quality of life. Side effects from SSRI's include gastrointestinal symptoms, anxiety, sleep disturbance, and sexual dysfunction. Evidence from recent clinical trials and preclinical studies suggests that blockade of 5-HT2 receptors may have antidepressant effects when combined with reuptake blockade of serotonin at serotonin transporters. In order to better determine whether 5-HT2A receptors are responsible for this effect we propose to study the highly specific and potent 5-HT2A antagonist, M100907, in combination with escitalopram in SSRI resistant major depression. Subjects aged 18-65 will be studied who prospectively are shown to be treatment resistant to the SSRI escitalopram. Subjects will be randomized in a doubleblind fashion to receive continued open treatment with escitalopram+M100907 or continued escitalopram+placebo. Subjects will have weekly mood and safety ratings during this randomized period for four weeks. At that time subjects who were initially
8
These are listed at www.ClinicalTrials.gov.
118 Antidepressants
randomized to placebo (and are non-responders) will be switched to active drug for four weeks of randomized treatment while the active group continues an additional four weeks of combination therapy. Those meeting remission criteria will be eligible to extend therapy in open treatment with the combination therapy for an additional period of up to 6 months. Due to the potential for M100907 to improve sleep architecture in general and slow wave sleep in particular, sleep will be studied using polysomnographic methods before and after randomization. Sleep disturbance is also a well-known side effect of SSRI's, and the addition of M100907 may improve sleep disturbance related to the affective disorder itself or to iatrogenic SSRI effects on sleep. Examination of improvement in sexual side effects, gastrointestinal side effects, headache frequency, and anxiety will also be investigated in the comparison of addition of M100907 versus placebo in escitalopram treated subjects. DNA samples will be collected for neurotransmitter-related genetic polymorphisms for covariance. Finally, 5HT2A receptors on cortical apical dendrites sit in a crucial location to influence cognitive processing and excitatory transmission. Since some 5-HT2A antagonists can lead to a down-regulation of 5-HT2A receptors and their altered distribution, as well as increased prefrontal cortical monoamine levels, neuropsychological testing to compare between and within subjects treated with M100907 and placebo may increase our understanding of the importance of serotonin receptors in cognition and depression. Subjects will be studied neuropsychologically before and twice following randomization. If M100907 enhances cognition in depression this would be an important advance given the high rates of impairment in functioning and residual cognitive difficulties observed in patients with depression. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070694 •
Antidepressant Treatment for Premenstrual Syndrome and Premenstrual Dysphoric Disorder Condition(s): Premenstrual Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine whether women with moderate to severe Premenstrual Syndrome (PMS) are willing and able to adhere to drug treatment that is limited to half of their menstrual cycle. This study will also determine whether patient characteristics influence response to treatment with serotonin reuptake inhibitors (SRIs) and whether SRIs can alleviate premenstrual symptoms. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048854
•
Antidepressant Treatment in Late Life Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients.
Clinical Trials 119
Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of citalopram (Celexa) for the treatment of depressive symptoms in middle-aged and elderly patients with schizophrenia. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046098 •
Antidepressant Treatment in Older Patients with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of citalopram (Celexa) for the treatment of depressive symptoms in middle-aged and elderly patients with schizophrenia. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047450
•
Antidepressant Treatment of Melancholia in Late Life Condition(s): Depression; Melancholia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare the safety and effectiveness of a select serotonin re-uptake inhibitor (SSRI, sertraline) and a tricyclic antidepressant (TCA, nortriptyline) in outpatients over the age of 60 who have major depression. SSRIs are effective in the treatment of major depression. However, there is also evidence that SSRIs may be significantly less effective than TCAs for patients with late-life major depression with melancholia. Since SSRIs seem to be easier to take than TCAs and are more widely prescribed, it is important to determine which of these types of antidepressants works best to treat these patients. Patients will be assigned randomly to receive either sertraline (a SSRI) or nortriptyline (a TCA) for 12 weeks. Patients will be monitored for symptoms, side effects, and quality of life. If a patient responds to treatment, he/she will participate in a 6-month continuation phase in which he/she will continue to receive the same medication. An individual may be eligible for this study if he/she: Has unipolar major depression (with some exceptions) and is over 60 years old. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000378
•
Biological Aspects of Depression and Antidepressant Drugs Condition(s): Depression Study Status: This study is currently recruiting patients.
120 Antidepressants
Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This study will be measuring changes in depressive symptoms over a 7 week time period. Double-blind placebo controlled trial using the pharmacologic agents Paroxatene or Desiprimine. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018733 •
Effect of Antidepressants on Back Pain Condition(s): Back Pain; Sciatica Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The purpose of this study is to determine whether different types of antidepressant medicines relieve back pain that has lasted at least six months on a daily basis. Study participants will be assigned to treatment with either a antidepressant acting on the serotonin system in the brain (fluoxetine), one acting on the noradrenoline system (desipramine, or to a control medication not expected to relieve pain (benztropine). Each participant will be seen at least nine times during their 12 weeks on medication. This is a phase 2/3, outpatient study. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018200
•
Ethnic Variations in Antidepressant Response Condition(s): Depression; Depressive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine how genetic factors affect the way patients with major depression respond to antidepressant medication. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047671
•
Ginkgo Biloba: Antidepressant-Induced Sexual Dysfunction Condition(s): Hypoactive Sexual Desire Disorder; Sexual Dysfunctions, Psychological Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to provide the first empirical examination of the effects of Ginkgo biloba (GBE), sex therapy, and a combination of the
Clinical Trials 121
two on subjective and physiological measures of sexual function in women who are experiencing sexual disorders secondary to antidepressants. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034021 •
Improving Hispanic Retention in Antidepressant Therapy Condition(s): Depression; Depressive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to develop an intervention that will increase the retention of Hispanics with major depression in antidepressant therapy. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057642
•
Platelet Function in Patients Treated with SSRI and non-SSRI Antidepressants Condition(s): Depression Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will examine the effect of a class of antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) on platelet function. Platelets are small blood cells that help stop bleeding after injury to a blood vessel by forming a clot, or plug, in the vessel. Some medications impair platelet function, leading to increased bruising and bleeding. SSRIs decrease an important platelet component called serotonin, which may cause bleeding in some patients. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox) and citalopram (Celexa). Patients 18 years of age and older being treated for depression with a SSRI or the non-SSRI bupropion (Wellbutrin) may be eligible for this study. Subjects will be recruited from a private clinic in Washington, D.C. Participants will provide a history of their current medications and past history of bleeding. They will have about 4 tablespoons of blood drawn for tests to measure blood cell counts and platelet function. The study takes about 1 hour. The results of the SSRI-treated group and the bupropiontreated group will be analyzed and compared. This study may provide information that will help health care providers make treatment decisions to minimize possible adverse effects of medications in patients with depression. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009568
•
Sexual Functioning Study With Antidepressants Condition(s): Major Depressive Disorder
122 Antidepressants
Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: Effects of two depression medications on sexual functioning Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051259 •
Sexual Functioning Study With Antidepressants In Adults Condition(s): Major Depressive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: Effects of two antidepression medications on sexual functioning Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051272
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “antidepressants” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
•
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
•
For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
•
For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
Clinical Trials 123
•
For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
•
For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
•
For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
•
For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
•
For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
•
For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
•
For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
•
For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
•
For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
•
For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
•
For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
125
CHAPTER 6. PATENTS ON ANTIDEPRESSANTS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “antidepressants” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on antidepressants, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Antidepressants By performing a patent search focusing on antidepressants, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
126 Antidepressants
example of the type of information that you can expect to obtain from a patent search on antidepressants: •
3-Hydroxy-propanamine derived neuronal reuptake inhibitors Inventor(s): Carlier; Paul R. (Kowloon, HK), Lo; Ching Kam (North Point, HK), Lo; Man Chu (Cambride, MA), Richelson; Elliott (Ponte Vedra Beach, FL) Assignee(s): The Hong Kong University of Science and Technology (Kowloon, HK) Patent Number: 6,069,177 Date filed: July 8, 1997 Abstract: 3-Hydroxy-propanamine derivatives and acid salts thereof having chiral centers at the C.sub.1 and C.sub.2 positions exhibit synaptosomal reuptake inhibition of neurotransmitters, and as such represent a new class of psychotropic agents useful as antidepressants. Excerpt(s): The invention is a new class of antidepressant compounds which exhibit synaptosomal reuptake inhibition of neurotransmitters such as serotonin (5-HT), norepinephrine (NE), and dopamine (DA). The invention is a class of 3-hydroxypropanamine compounds having chiral centers at the C.sub.1 and C.sub.2 positions. Effexor.RTM. and Serzone.RTM. have been termed SNRI antidepressants because they inhibit 5-HT and NE reuptake with similar potency. To achieve an effective therapy for patients for whom present drugs are ineffective, it would be desirable to have drugs which possess reuptake inhibition profiles different from those currently known. Pinder and Wieringa have commented that an agent which simultaneously inhibits reuptake of 5-HT, NE, and DA could be the ultimate reuptake-inhibiting antidepressant drug (Med. Res. Rev., 13, 259-325 (1993)). The present invention provides the first examples of such drugs. R.sub.5 and R.sub.6 are independently hydrogen or C.sub.1 to C.sub.6 alkyl. Web site: http://www.delphion.com/details?pn=US06069177__
•
4-phenyl-1,3-benzodiazepines and 2-amino-.alpha.-phenylphenethylamines treating convulsions and protecting neurons
for
Inventor(s): Crichlow; Charles A. (Stockton, CA), Martin; Lawrence L. (Lebanon, NJ), Worm; Manfred (Wiesbaden-Naurod, CA) Assignee(s): Hoechst-Roussel Pharmaceuticals Incorporated (Somerville, NJ) Patent Number: 5,260,339 Date filed: October 8, 1992 Abstract: Novel 4-phenyl-1,3-benzodiazepines and 2-amino-.alpha.phenylphenethylamines, novel intermediates thereof, and methods of preparing same are described. These benzodiazepines are useful as antidepressants, analgetics and anticonvulsants. The 2-amino-.alpha.-phenylphenethylamines are useful as anticonvulsant and neuroprotective agents. Excerpt(s): Preferred compounds of the present invention are those in which R and R.sub.1 are alkyl of from 1 to 5 carbon atoms. Particularly preferred compounds are those wherein R is methyl or ethyl and R.sub.1 is methyl. In the above intermediates, anticonvulsants and neuron protectors, i.e., the phenethylamines and the corresponding acyl derivatives thereof, preferred compounds are those in which R.sub.1 is alkyl of
Patents 127
from 1 to 5 carbon atoms. Particularly preferred compounds are those in which R.sub.1 is methyl. The physiologically acceptable salts of the present invention are acid addition salts which may be prepared from inorganic acids such as hydrochloric, hydrobromic, sulfuric, nitric, phosphoric and perchloric acids, as well as from organic acids such as tartaric, citric, acetic, succinic, maleic, fumaric and oxalic. Web site: http://www.delphion.com/details?pn=US05260339__ •
Agent with an antidepressant activity Inventor(s): Bechtel; Wolf-Dietrich (Appenheim, DE), Lehr; Erich (Waldalgesheim, DE), Schuster; Astrid (Ingelheim am Rhein, DE) Assignee(s): Boehringer Ingelheim GmbH (Ingelheim am Rhein, DE) Patent Number: 5,217,967 Date filed: September 6, 1991 Abstract: An improved process for employing tricyclic antidepressants involving coadministration of a N-benzyl-pyrrolidin-2-one. Excerpt(s): The invention relates to an agent with an antidepressant activity containing a compound A and a compound B. A number of tricyclic antidepressants are known from the literature, containing as their central structural element a 10,11-dihydrodibenzo[b,f]azepine structure, a dibenzo[a,d][1,4]cycloheptadiene structure or a [10,11]dihydro-dibenzo[b,f]oxepine structure. On the one hand, these compounds have excellent antidepressant properties and have proved useful in therapy. On the other hand their therapeutic range of application is considerably limited by undesirable side effects, such as cardiotoxicity and proconvulsive activity. Web site: http://www.delphion.com/details?pn=US05217967__
•
Antidepressant 3-halophenylpiperazinylpropyl derivatives of substituted triazolones and triazoldiones Inventor(s): Luke; George M. (LaFayette, NY), Mayol; Robert F. (Durham, CT) Assignee(s): Bristol-Myers Squibb Company (New York, NY) Patent Number: 5,256,664 Date filed: April 28, 1992 Abstract: 2-(3-[4-(3-Halophenyl)-1-piperazinyl]propyl derivatives of certain 4-alkyl- or 4-phenoxyalkyl-2,4-dihydro-3H-1,2,4-triazol-3-ones and triazol-3,5-diones are psychotropic agents having promise as antidepressants by virtue of their receptor site binding affinity profiles and animal pharmacology. Excerpt(s): The present invention relates to 1,2,4-triazole heterocyclic carbon compounds, their preparation, metabolic transformations and use. More particularly, the invention relates to keto and triazoldione analogs of the antidepressant agent nefazodone. In its broadest aspect, the instant invention is concerned with structural variation at the 5-position of the 3H-1,2,4-triazol-3-one ring of nefazodone and its related analogs. The compounds of the present invention are characterized by replacement of the 5-ethyl-group by an acetyl group (Ia) or by transformation of the 5position to a carbonyl moiety (Ib). The invention also concerns the discovery that
128 Antidepressants
compounds of the present invention are psychotropic agents displaying selective central nervous system effects which are associated with useful antidepressant activity. The more preferred compounds of the present series have the structures of Formula XIb, and in the most preferred compounds of Formula XIb, Z is a phenoxy moiety. For medicinal use, the pharmaceutically acceptable acid addition salts, those salts in which the anion does not contribute significantly to toxicity or pharmacological activity of the organic cation, are preferred. The acid addition salts are obtained either by reaction of an organic base of structure I with an inorganic or organic acid, preferably by contact in solution, or by any of the standard methods detailed in the literature and available to any practitioner skilled in the art. Examples of useful organic acids are carboxylic acids such as maleic acid, acetic acid, tartaric acid, propionic acid, fumaric acid, isethionic acid, succinic acid, pamoic acid, cyclamic acid, tannic acid, and the like; useful inorganic acids are hydrohalic acids such as HCl, HBr, HI; sulfuric acid, phosphoric acid; and the like. Web site: http://www.delphion.com/details?pn=US05256664__ •
Antidepressants Inventor(s): Freedman; Jules (Cincinnati, OH) Assignee(s): Merrell Pharmaceuticals Inc. (Cincinnati, OH) Patent Number: 5,561,152 Date filed: December 6, 1994 Abstract: The present invention provides novel aryloxy indanamines which are useful as anti-depressants and as inhibitors of synaptic norepinephrine and serotonin uptake. Excerpt(s): or an acid addition salt thereof. The aryloxy moiety of compounds of formula (1) can be mono- or di-substituted at any feasible position(s) in the ring (when q is 1 or 2, respectively) or it can be unsubstituted (when q is 0). X is independently chosen each time it is taken so that when q is 2 the aryloxy moiety is di-substituted with the same or different substituents. Likewise, the fused-ring moiety can be mono- or di-substituted at any of the 4, 5, 6, or 7 position(s) (when p is 1 or 2, respectively) or it can be unsubstituted (when p is 0). Y is independently chosen each time it is taken so that when p is 2 the fused-ring moiety is di-substituted with the same or different substituents. R.sub.1 and R.sub.2 can be independent moieties or they can be taken together with the nitrogen to which they are attached to form a pyrrolidino, morpholino, piperidino, piperazino, or 4-methylpiperazino group. As used herein, the term "lower alkyl" refers to an alkyl group comprised of 1 to 6 carbon atoms in straight, branched, or cyclic configuration. The term "lower alkoxy" refers to a lower alkyl group substituted with a single oxygen atom which is attached to the appropriate aryl carbon. The term "halogeno" refers to a fluoro, chloro, bromo or iodo substituent. The term "methylenedioxy" refers to a --O--CH.sub.2 --O-- moiety attached to adjacent aryl carbon atoms. The term "aralkyl" refers to an aromatic ring attached to the nitrogen atom by a C.sub.1 to C.sub.4 alkylene bridge. For example, the term "aralkyl" includes, but is not limited to benzyl, and the like. Web site: http://www.delphion.com/details?pn=US05561152__
Patents 129
•
Bridged bicyclic imides as anxiolytics and antidepressants Inventor(s): Bright; Gene M. (Groton, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 5,242,911 Date filed: May 23, 1989 Abstract: A series of bridged bicyclic imide compounds having a 4-(4-[2-pyrimidinyl]-1piperazinyl)butyl group attached to the imide nitrogen are useful for alleviating the symptoms of anxiety and depression in human subjects. Excerpt(s): Anxiety and depression are common afflictions which adversely affect a significant portion of the human population. Both anxiety and depression can appear as either acute or chronic disease states, and in certain subjects these disease states can coexist. It has been known for many hears that the symptoms of anxiety and depression in human subjects can often be alleviated by the administration of certain chemical substances. In this regard, compounds which are used to treat anxiety are called antianxiety agents, or anxiolytics; while compounds which are used to treat depression are normally termed antidepressants. In modern medical practiace, a widely-used class of anxiolytics is the benzodiazepines, such as diazepam, and common antidepressants are the so-called "tricyclics," such as imipramine. However, benzodiazepines also have sedative properties in addition to their antianxiety properties. Moreover, tricyclic antidepressants often exhibit undesirable cardiovascular and anticholinergic sideeffects. Web site: http://www.delphion.com/details?pn=US05242911__
•
Invertebrate phenylethanolamine transporter and the use thereof Inventor(s): Nathanson; James A. (Wellesley, MA) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 5,366,975 Date filed: December 28, 1992 Abstract: A method of controlling an invertebrate pest, comprising contacting the pest with a pest-controlling amount of an agent having substantial inhibitory activity toward a phenylethanolamine reuptake transporter as determined by radioactive octopamine reuptake inhibition assay is disclosed. Compositions comprising compounds capable of inhibiting the octopamine reuptake transporter include chloroethylphenylamines, aryl1,4-dialkyl piperazines, tricyclic antidepressants, and cocaine derivatives. A process for inhibiting the feeding of an invertebrate pest comprising contacting said pest with a pest-controlling amount of an agent having substantial inhibitory activity toward a phenylethanolamine reuptake transporter as determined by radioactive octopamine reuptake inhibition assay, with the proviso that said agent is not cocaine. A process for delaying the maturation of a juvenile invertebrate by contacting it with an inhibitory amount of a phenylethanolamine reuptake transporter blocker is also disclosed. A radioactive phenylethanolamine reuptake inhibition assay for determining whether a given compound is an inhibitor of octopamine neuronal transport is also disclosed. Excerpt(s): The present invention is in the field of pest-controlling agents. In particular, the invention relates to a method for inhibiting an invertebrate-specific membrane transporter protein, compounds having binding specificity therefor, and
130 Antidepressants
pesticidal/pestistatic compositions. This invention also relates to an in vitro assay used to determine whether a given compound is an inhibitor of octopamine neuronal transport. Octopamine (OA) was first discovered over 35 years ago in the posterior salivary gland of the octopus (V. Erspamer and G. Boretti, Arch. Int. Pharmaco. Ther. 88: 926-322 (1951)). Although similar to norepinephrine (NE) in structure, OA has very little activity as a sympathomimetic when injected into mammals (A. Lands and J. Grant, J. Pharm. Exptl. Therap. 106: 341-345 (1952)) and, compared with NE, is present in very low concentrations in vertebrate tissues (Y. Kakimoto and M;. Armstrong, J. Biol. Chem. 237: 422-427 (1962)). Relatively little attention was paid to OA until early 1970's, when Molinoff and Axelrod reported that OA was present in much higher concentrations in invertebrates, particularly in invertebrate nerve tissue (P. B. Molinoff and J. Axelrod, J. Neurochem. 19: 157-163 (1972)). In 1973, the first identification of an OA receptor was reported (J. A. Nathanson "Cyclic AMP: A Possible Role in Insect Nervous System Function", (Ph.D. Thesis) (1973); J. A. Nathanson and P. Greengard, Science, 19: 308-310 (1973)). Because this receptor was present in highest concentrations in insect nerve cord, it was postulated that OA might function as a neurotransmitter. Furthermore, because these receptors were undetectable in mammalian tissues, it was also postulated that the neurotransmitter function of OA might be largely restricted to invertebrates (J. A. Nathanson "Cyclic AMP: A Possible Role in Insect Nervous System Function", (Ph.D. Thesis) (1973); J. A. Nathanson and P. Greengard, Science, 19: 308-310 (1973); J. A. Nathanson, Trace Amines and the Brain: Eds. Marcel Dekker, pp. 161-190 (1976)). At about the same time, Kravitz and coworkers (B. Wallace et al., Brain Res. 349-55 (1974)) independently reported the presence of OA-containing neurons in crustacea, and, somewhat later, Hoyle reported evidence suggesting the presence of large OA neurons in insect ganglia (G. Hoyle, J. Exp. Zool 193: 425-31 (1975)). Subsequent work by a number of investigators has established the role of OA, not only as a neurotransmitter, but also as a neuromodulator and circulating neurohormone in insects and acarines (for review see I. Orchard, Can. J. Zool, 60: 659-69 (1982); H. A. Robertson and A. V. Juorio, Int. Rev. Neurobiol. 19: 173-224 (1976)). Indeed, OA plays a pervasive role in regulating many areas of insect physiology, including carbohydrate metabolism, lipid mobilization, hematocyte function, heart rate, peripheral muscle tension and excitability, and behavior. The functions that OA carries out in insects appear analogous to those carried out by norepinephrine (NE) and epinephrine (EPI) in vertebrates. This has led to the suggestion that, during evolution, there may have been a divergence in the use of these amines between the two arms of the animal kingdom (H. A. Robertson and A. V. Juorio, Int. Rev. Neurobiol. 19: 173-224 (1976); A. V. Robertson and A. V. Juorio, J. Neurochem. 28: 573-79 (1977); J. A. Nathanson, Physiological Reviews 57: 158-256 (1977)). Web site: http://www.delphion.com/details?pn=US05366975__ •
Method for the preparation of aryl ethers Inventor(s): Henegar; Kevin E. (Portage, MI), Maisto; Keith D. (Portage, MI), Mancini; Sarah E. (Kalamazoo, MI) Assignee(s): Pharmacia and Upjohn Company (Kalamazoo, MI) Patent Number: 6,376,711 Date filed: December 23, 1999 Abstract: The invention relates to a method for preparing aryl ethers that are useful as antidepressants. The invention also relates to intermediates useful in the method and to methods for preparing such intermediates.
Patents 131
Excerpt(s): The present invention relates to an improved method for preparing certain aryl ethers that are useful as antidepressants. The invention also relates to intermediates useful in the method, and to methods for preparing such intermediates. or a pharmaceutically acceptable salt thereof. The compounds are disclosed to possess antidepressant activity. Web site: http://www.delphion.com/details?pn=US06376711__ •
Method of modifying angiotensin receptor activity for mediation of pain Inventor(s): dePadova; Anthony S. (49 Dexter Dr. North, Basking Ridge, NJ 07920) Assignee(s): none reported Patent Number: 5,753,651 Date filed: October 25, 1996 Abstract: The present invention relates to a method of modifying Angiotensin II subtype 1 (AT.sub.1) receptor activity for the treatment of premenstrual syndrome (PMS) and the symptoms associated therewith, and further relates to a method for the treatment of acute or chronic pain mediated by the sympathetic nervous system. The treatment includes the administration of an effective amount of an AT.sub.1 antagonist. AT.sub.1 antagonists are drugs that are capable of blocking AT.sub.1 receptors present within the body throughout the central nervous system including the hypothalamus. By blocking the AT.sub.1 receptor activity, hypothalamic nerve activity, and therefore, sympathetic nerve activity are modulated. Thus, an effective method for treating sympathetically mediated pain is provided, as well as an effective method for treating PMS. The AT.sub.1 antagonist can be used alone or in combination with other drug therapies, for instance, non-steroidal anti-inflammatory drugs, antidepressants, opiod drugs, angiotensin converting enzyme inhibitors, and diuretics. Excerpt(s): The present invention relates to a method of modifying Angiotensin II subtype 1 (AT.sub.1) receptor activity for the treatment of premenstrual syndrome (PMS) and for the mediation and alleviation of pain. More specifically, the present invention relates to the use of AT.sub.1 antagonists to modulate sympathetic nerve activity as treatment for pain and as treatment for PMS. The nervous system of the human body carries information in the form of nerve impulses to and from all parts of the body in order to regulate body activity. The nervous system consists of the central nervous system (CNS), including the brain and the spinal cord, which is responsible for integrating all activities of the nervous system; and the peripheral nervous system, including the cranial nerves and the spinal nerves, which link the receptors and the effector organs with the brain and spinal cord. The autonomic nervous system controls many bodily functions that are not consciously directed. The autonomic nervous system is subdivided into the sympathetic and the parasympathetic nervous systems, which individually control and coordinate various functions of body organs. It is well known that the hypothalamus is an area of the brain which integrates hormonal and autonomic activity within the body, and coordinates physiological, behavioral and mood responses. The hypothalamus is the major central controller of the autonomic nervous system. Nearly every region of the brain sends signals to the hypothalamus. Pathways of nerve fibers descend from the brain and connect through synapses with areas on the brain stem, and then descend to the spinal cord where they synapse with neurons in the lateral columns of white matter which represent collections of nerve cells. There is an intimate interconnection between the nerve pathways involved in pain transmission and the sympathetic nervous system. (Basic Neurochemistry, Raven Press, 1994).
132 Antidepressants
Web site: http://www.delphion.com/details?pn=US05753651__ •
Optically active aminopentane derivatives Inventor(s): Ando; Takashi (Matsubara, JP), Knoll; Joseph (Budapest, HU), Moto; Toshiaki (Matsubara, JP), Ohde; Hironori (Matsubara, JP), Sakae; Masatoshi (Matsubara, JP), Shimazu; Seiichiro (Matsubara, JP), Takahata; Kazue (Matsubara, JP), Yoneda; Fumio (Matsubara, JP) Assignee(s): Fujimoto Brothers Co., Ltd. (Osaka, JP) Patent Number: 6,391,914 Date filed: June 16, 2000 Abstract: A novel optically pure (-)-1-(Benzofuran-2-yl)-2-propylaminopentane as represented by the following formula, which contains no (+)-isomer, and the pharmaceutically acceptable acid salt thereof. These compounds have excellent CAE effect (catecholaminergic activity enhancer effect) which is the enhancing action of neurotransmitter catecholamine release, and are useful as psychotropic composition, antidepressants, composition for treating Parkinson's disease and/or Alzheimer's disease. Excerpt(s): The invention relates to a novel optically active aminopentane derivative, (-)1-(benzofuran-2-yl)-2-propylaminopentane, which contains substantially no (+)-isomer, and to the pharmaceutically acceptable acid salts thereof. These are promising as active compounds of a pharmaceutical composition, especially, psychotropic composition, antidepressant, composition for treating Parkinson's disease and/or Alzheimer's disease. The ethylamine derivatives are known to have various biological actions. Particularly, aromatic ethylamine derivatives are thought to be hopeful as psychotropic composition, because they have the releasing action of displacing catecholamines from their storage places in the central nervous system. However, it is pointed out that these compositions have stimulant-like side effects such as neurotoxicity and abnormal behavior, because they easily cause excess catecholamine release from storage places, i.e. synaptic vesicles and so on. The continuous administration of these compositions, which enhance the excess catecholamine release, induces the decrease of catecholamine receptors. Consequently, the response of patients to these compositions is gradually reduced and no sufficient therapeutic effect can be obtained. On the other hand, novel phenethylamine derivatives had been disclosed in WO 88/2254 as a psychotropic composition and so on. Considerable attention has been paid to these phenethylamine derivatives, because these showed the catecholaminergic activity enhancer effect (CAE effect), which is a newly discovered action to enhance the catecholamine release due to amplification of the membrane potential dependent exocytosis, and which is different from the above releasing action by displacing catecholamine from their storage [Life Sci., 58, 945-952 (1996)]. However, these compounds did not settle the increase of the intersignal reaction that is an indicator of abnormal behavior in the conditioned avoidance task. Therefore, the development of highly selective CAE drug has been required. Then, we had developed novel compounds enhancing catecholamine release by CAE effect, and found them useful as a psychotropic composition, antidepressants, composition for the treatment of Parkinsons's disease and/or of Alzheimer's disease (patent application No. JP 9/247445). Web site: http://www.delphion.com/details?pn=US06391914__
Patents 133
•
Smoking cessation treatments using naltrexone and related compounds Inventor(s): Krishnan-Sarin; Suchitra (Durham, CT), Meandzija; Boris (Hamden, CT), O'Connor; Patrick G. (Woodbridge, CT), O'Malley; Stephanie (New Haven, CT) Assignee(s): Yale University (New Haven, CT) Patent Number: 6,004,970 Date filed: November 12, 1997 Abstract: Nicotine dependency is treated by administration of an opioid antagonist. In some embodiments, rapid or ultra rapid detoxification techniques include using a combination of an effective amount of an opioid antagonist such as nalmefene, naloxone or naltrexone or a mixture of any one of these, and either clonidine or related compounds either while awake, or while under sedation or anesthesia, followed by continued administration of an effective amount of an opioid antagonist with or without agents that enhance nicotine dependency treatment. Persons are also treated for nicotine dependency with more gradual detoxification methods using administration of a combination of an effective amount of an opioid antagonist such as nalmefene, naloxone, naltrexone, or a mixture of any of these, and an effective amount of agents used to treat nicotine withdrawal including nicotine, such as that delivered by a nicotine patch, nicotine chewing gum, nicotine inhaler or other methods for delivering nicotine, antidepressants and antianxiety agents, and/or clonidine and related compounds. Administration of an effective amount of an opioid antagonist to prevent relapse, attenuate craving, and reduce weight gain during and after treatment for nicotine dependency is continued in some embodiments. Excerpt(s): This invention relates to the use of opioid antagonists such as naltrexone, naloxone or nalmephene alone or with either nicotine replacement therapy or with other withdrawal attenuating agents, to increase smoking abstinence rates, to decrease craving for cigarettes, reduce relapse to heavy smoking during detoxification or once smoking abstinence has been achieved, and to reduce weight gain associated with smoking cessation. Tobacco dependence continues to be a major health hazard for millions of Americans, and because smoking may pose a health risk for non-smokers as well, smoking cessation treatments are of great public interest. Dependence is an adaptive biological state induced by chronic drug exposure which manifests itself in various behavioral and physiological responses when drug exposure ceases. Withdrawal from nicotine following chronic use of tobacco products results in the emergence of an abstinence syndrome which reaches its peak intensity within the first day. Cessation of smoking has been shown to result in a number of signs and symptoms of withdrawal such as increases in irritability, anxiety, restlessness, impatience, somatic complaints, cigarette craving, hunger, insomnia, tremulousness and heart rate as well as difficulty concentrating, all of which are collectively called the tobacco withdrawal syndrome. Web site: http://www.delphion.com/details?pn=US06004970__
134 Antidepressants
•
Stabilized solutions of psychotropic agents Inventor(s): Mentink; Maria M. F. (Oss, NL), Van Den Oetelaar; Petrus J. M. (Heesch, NL) Assignee(s): Akzo N.V. (Arnhem, NL) Patent Number: 5,208,261 Date filed: October 1, 1991 Abstract: Disclosed are stabilized aqueous preparations containing an antidepressant in admixture with a stabilizing compound such as L-methionine, D-methionine, DLmethionine, or mixtures thereof. The stabilized preparations display better stability when exposed to light, relatively high temperatures, time, and peroxides resulting in longer shelf-lives. Antidepressants which are stabilized include mirtazapine, mianserin, septiline, and amitriptyline. Excerpt(s): This invention relates to pharmaceutical compositions generally, and to stabilized aqueous solutions of certain antidepressant drugs specifically. Solutions of certain antidepressants (e.g., amitriptyline) are not very stable. They discolor, form particles, and/or suffer a decrease in concentration under certain conditions. For example, they may discolor or show a decrease in concentration upon exposure to light; upon the formation of peroxides in, or addition of peroxides to, the solutions; or when such solutions are stored at elevated temperatures. Particles may also form in such solutions under these conditions. Discoloration, development of opalescence, a decrease in concentration, and particle formation are all tokens of instability. These tokens of instability may occur rather rapidly, sometimes within days, forcing the dispensing pharmacist to mix new solutions frequently. An attempt to stabilize dry pharmaceutical preparations containing amitriptyline oxide dihydrate is described in German Patent Application DE 3247676 A1, published on Jun. 28, 1984 (corresponding to U.S. Pat. No. 4,567,202). That patent application describes a composition containing amitriptyline oxide dihydrate and an organic acid including certain listed amino acids. The organic acid, especially citric acid, is used to stabilize the amitriptyline. Web site: http://www.delphion.com/details?pn=US05208261__
•
Use of antidepressants for local analgesia Inventor(s): Esser; Mike (Nova Scotia, CA), Reid; Allison (Nova Scotia, CA), Sawynok; Jana (Nova Scotia, CA) Assignee(s): Dalhousie University (Nova Scotia, CA) Patent Number: 6,211,171 Date filed: May 19, 1998 Abstract: When administered locally, tricyclic, second generation and third generation antidepressants, such as amitriptyline and desipramine, have been shown to produce analgesia in a subject having a site of local discomfort. The analgesic effect of such antidepressants, when administered locally is equal to that achieved by systemic administration and lasts longer. The invention provides compositions containing tricyclic, second generation, and third generation antidepressants for local administration, such as those formulated for topical application, or for injection in slow release delivery vehicles, and methods for their use for producing local analgesia.
Patents 135
Excerpt(s): The present invention relates to therapeutic compositions and methods for their use. In a particular aspect, the present invention relates to compositions for producing pain relief and methods of their use. Neuropathic pain is a form of chronic pain that can persist for months, years or decades following an injury, and results from damage to peripheral nerves, nerve roots, the spinal cord or certain brain regions. It differs from nociceptive pain in terms of duration, characteristics, underlying mechanisms and treatment (Bennett G. J. (1994a) In: Textbook of Pain (Ed. Wall P D, Melzack R) Churchill Livingstone, London 3rd edn, 201). Neuropathic pain can consist of spontaneous pain (e.g., burning, cutting, tingling), evoked pain (e.g., allodynia evoked by stimulation of non-nociceptive afferents, and hyperalgesia evoked by stimulation of nociceptive afferents) and paroxysmal pain (e.g., originating from a trigger point, described as stabbing, lancinating, shocklike) (Bennett G. J. (1994a) In: Textbook of Pain (Ed. Wall P D, Melzack R) Churchill Livingstone, London 3rd edn, 201). Neuropathic pain can accompany nociceptive pain, and multiple treatment strategies may be required for optimal alleviation of pain (Portenoy R. K. (1991) In: Towards a New Pharmacology of Pain (Ed. Basbaum A I, Besson J. M.) John Wiley & Sons Ltd, New York, 393; Devor M, Basbaum A. I., Bennett., Blumeberg H, Campbell et al (1991) In: Towards a New Pharmacotherapy of Pain (Ed. Basbaum A I, Besson J. M.) John Wiley & Sons, New York, 417). Neuropathic syndromes are traditionally classified according to the disease or event that precipitated them (e.g., postherpetic neuralgia following shingles, causalgia following partial damage to a major nerve, central pain following a thalamic infarct) (Portenoy R. K. (1991) In: Towards a New Pharmacology of Pain (Ed. Basbaum A. I., Besson J. M.) John Wiley & Sons Ltd, New York, 393; Merskey H, Bogaduk N (1994) In: Classification of Chronic Pain. Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms, 2nd edn, IASP Press, Seattle, page 40). The involvement of the sympathetic nervous system in a number of these conditions has been appreciated for some time. Pain syndromes with a sympathetic component are considered as sympathetically maintained pain (reflect sympathetic dystrophy, causalgia) (Bonica J. J. (1990) In: The Management of Pain (Ed. Bonica J. J.) Lea & Fibiger, Philadelphia 2nd edn. Bonica (1990, 220; Blumeberg H., Janig W. (1994) In: Textbook of Pain (Ed. Wall P D, Melzack R) Churchill Livingstone, London 3rd edn, 685). Neuropathic pain is particularly difficult to treat clinically. The use of opioids is controversial, with issues of contention being the relative refractoriness of neuropathic pain compared to nociceptive pain, the need for higher doses with an increased incidence of side effects to achieve partial effects, and concerns over the long term use of opioids in a non-malignant context (Arner S, Meyerson B A (1988) Pain 22: 11; Kuypers H., Konig H., Adriaenson H., Gybels J. M. (1991) Pain 47: 5; Portenoy R. K., Foley K. M., Inturrisi C. E. (1990) Pain 43: 273; Portenoy R. K. (1994) In: Progress in Pain Research and Management (Ed. Fields H. L., Liebskind J. C.) IASP Press, Seattle, 247). The major classes of agents currently used to treat neuropathic pain include systemically delivered antidepressants, anticonvulsants, local anesthetics, and specialized agents such as muscle relaxants, and sympatholytic drugs (reviewed Portenoy R. K. (1991) In: Towards a New Pharmacology of Pain (Ed. Basbaum A I, Besson J. M.) John Wiley & Sons Ltd, New York, 393; Portenoy R. K. (1993) Drug Therapy 23: 41; Max M B (1994) In: Progress in Pain Research and Management (Ed. Fields H. L., Liebskind J. C.) IASP Press, Seattle, 229). However, many of these treatments show limited effectiveness (complete pain relief is rarely achieved), and there is a high incidence of debilitative side effects (Portenoy R. K. (1993) Drug Therapy 23: 41; Bennett G. J. (1994a) In: Textbook of Pain (Ed. Wall P D, Melzack R) Churchill Livingstone, London 3rd edn, 201; Mac Farlane et al., (1997) Pharmacol. Ther. 75:1). Web site: http://www.delphion.com/details?pn=US06211171__
136 Antidepressants
•
Use of certain affinity NMDA antagonists as antidepressants Inventor(s): McCarthy; Dennis J. (Shrewsbury, MA) Assignee(s): AstraZeneca AB (Sodertalje, SE) Patent Number: 6,479,553 Date filed: May 12, 2000 Abstract: The invention relates to the use of certain pharmaceutical compounds as antidepressant agents. Excerpt(s): The present invention relates to the use of certain pharmaceutical compounds as antidepressants. Compounds having NMDA (N-methyl-D-aspartate) antagonist activity are known in the art, for example see Watkins et al., Trends in Pharmacological Science, 11:25, 1990. In particular, certain compounds are disclosed in EP 279 937 and EP 633 879 as having NMDA antagonist activity and as being useful for treating various CNS disorders such as epilepsy. It has now surprisingly been found that the low affinity NMDA antagonist compounds of EP 633 879 as exemplified by (S)1-phenyl-2-(2-pyridyl)ethanamine, have activity in the mouse forced swim test, indicating that such compounds are potentially useful as antidepressant agents. In particular, low affinity NMDA antagonists such as (S)-1-phenyl-2-(2pyridyl)ethanamine are expected to be useful in the treatment of depression associated with neurodegenerative disorders such as Alzheimer's disease. The compound (S)-1phenyl-2-(2-pyridyl)ethanamine is particularly advantageous in that neither stimulation nor sedation are observed as side effects. Web site: http://www.delphion.com/details?pn=US06479553__
Patent Applications on Antidepressants As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to antidepressants: •
Antidepressant Inventor(s): Butterweck, Veronika; (Muenster, DE), Nishibe, Sansei; (Hokkaido, JP), Sasaki, Tsutomu; (Chiba, JP), Seo, Shujiro; (Chiba, JP) Correspondence: BIRCH STEWART KOLASCH & BIRCH; PO BOX 747; FALLS CHURCH; VA; 22040-0747; US Patent Application Number: 20020090403 Date filed: November 1, 2001 Abstract: The present invention provides (1) an Apocynum extract containing not less than 4% of flavonoid compounds, (2) an antidepressant composition (in the form of a food, dietary supplement or medicine) containing the Apocynum extract, and (3) a method for treating depression using the Apocynum extract.
10
This has been a common practice outside the United States prior to December 2000.
Patents 137
Excerpt(s): The present invention relates to novel Apocynum extracts, antidepressant compositions containing the Apocynum extracts in the form of foods, dietary supplements, medicines and the like, and methods for treating depression using the Apocynum extracts. The etiology of depression has been extensively discussed by many works, but has not been sufficiently explained yet. Various factors seem to be involved in the etiology and complicated with each other. Possible factors include biological factors such as neurochemical and genetic findings as well as situational or psychosociological factors such as previous personality or life stress. Clinical features of depression include depressive state, anhedonia (the inability to enjoy themselves), psychomotor inhibition, incoherence of thought/cognition, anxiety and agitation, physical (autonomic) symptoms, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Antidepressant effect of norepinephrine uptake 2 inhibitors and combined medications including them Inventor(s): Mooney, John J.; (Belmont, MA), Schildkraut, Joseph J.; (Chestnut Hill, MA) Correspondence: JOHN W. FREEMAN, ESQ.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020013312 Date filed: March 16, 2001 Abstract: Norepinephrine uptake 2 inhibitors (or their precursors) are administered to enhance the effect of norepinephrine reuptake inhibitors and other antidepressants. The uptake 2 inhibitor may be combined in a single medication with a norepinephrine reuptake inhibitor, such as imipramine, desipramine, or reboxetine, in order to inhibit both uptake mechanisms. The norepinephrine uptake 2 inhibitors may also be combined with MAO inhibitors or with selective serotonin reuptake inhibitors. Alternatively, the norepinephrine uptake 2 inhibitors may be useful antidepressants in their own right, without the need for co-administration of other antidepressants. One class of norepinephrine uptake 2 inhibitors is normetanephrine (the O-methylated metabolite of norepinephrine) and normetanephrine precursors [such as 3-(4-hydroxy-3methoxyphenyl)-serine (4H-3MePS ), particularly L-threo-3-(4-H-3MePS)]that are transported to the brain where they are converted into normethanephrine, thereby enhancing the effect of other antidepressants. For example, the invention enhances the antidepressant effect of norepinephrine reuptake inhibitors. Excerpt(s): This invention is in the general field of central nervous system medications, particularly antidepressants. Norepinephrine is released from presynaptic noradrenergic neurons into the synapse. One therapy for clinical depression is administration of drugs known as norepinephrine reuptake inhibitors, such as imipramine, desipramine, or reboxetine, which inhibit the reuptake of norepinephrine into the presynaptic neuron ("uptake 1"), the main mechanism of inactivating norepinephrine at the synapse. Reuptake inhibition thus increases synaptic norepinephrine levels. [Bolden-Watson and Richelson, Life Sciences, 52:1023-1029 (1993), hereby incorporated by reference, discloses a method for determining reuptake inhibition.]Typically these drugs are administered chronically and there may be a significant delay, e.g. 4-6 weeks, between the onset of therapy and clinical improvement. Other therapies feature the administration of other classes of drugs, such as monoamine oxidase (MAO) inhibitors or selective serotonin reuptake inhibitors.
138 Antidepressants
Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Antidepressant therapy Inventor(s): Ayer, Atul D.; (Palo Alto, CA), Seroff, Sylvia; (Mountain View, CA), Wong, Patrick S.-L.; (Burlingame, CA) Correspondence: ALZA CORPORATION; P O BOX 7210; INTELLECTUAL PROPERTY DEPARTMENT; MOUNTAIN VIEW; CA; 940397210 Patent Application Number: 20010055614 Date filed: August 15, 2001 Abstract: An osmotic dosage from is disclosed for delivering an antidepressant for treating depression in a patient in need of antidepressant therapy. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/085,432, filed on May 14, 1998. This invention pertains to an improvement in a dosage form comprising an antidepressant drug. The invention concerns also a pharmaceutical composition comprising an antidepressant drug and a pharmaceutical carrier for the antidepressant drug. The invention relates further to a method for the treatment of depressive affective disorders in a patient. Antidepressant drugs are a recognized therapeutically accepted class of drugs used for the treatment of depression, particularly endogenous depression and sometimes reactive depression. One class of antidepressant drug used for these therapies is the tricyclic antidepressant drugs. The tricyclic antidepressant's efficacy in alleviating depression is clinically established in the management of health. Also, there is clinical support for the use of the tricyclic antidepressants in psychiatric disorders, such as in the management of depression accompanied by anxiety or agitation and panic attacks. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Antidepressants and their analogues as long-acting local anesthetics and analgesics Inventor(s): Gerner, Peter; (Weston, MA), Verrecchia, Donald K.; (Winchester, MA), Wang, Ging Kuo; (Westwood, MA) Correspondence: Edward R. Gates, Esq.; Chantal Morgan D'Apuzzo, Ph.D.; Wolf, Greenfield & Sacks, P.C.; 600 Atlantic Avenue; Boston; MA; 02210; US Patent Application Number: 20030096805 Date filed: April 4, 2002 Abstract: Methods and compositions of antidepressants and analogs thereof for inducing local long-lasting anesthesia and analgesia are provided. The methods and compositions are useful for alleviating acute and chronic pain, particularly useful for treating a localized pain. Excerpt(s): This application claims priority to and is a continuation in part of co-pending U.S. application Ser. No. 09/965,138 filed on Sep. 26, 2001, which claims priority to U.S. application Serial No. 60/235,432 filed on Sep. 26, 2000. This invention relates to the use of antidepressants and analogs thereof to produce local long-acting relief of different varieties of pain. To provide a better understanding of the invention it is necessary to distinguish between the two terms analgesia and anesthesia. Analgesia is defined as a condition in which nociceptive stimuli are sensed but are not interpreted as pain.
Patents 139
Anesthesia is a state characterized by total loss of sensation, the result of pharmacologic depression of nerve function. Thus, analgesia does not produce anesthesia whereas anesthesia produces analgesia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
As-needed administration of tricyclic and other non-SRI antidepressant drugs to treat premature ejaculation Inventor(s): Gesundheit, Neil; (Los Altos, CA), Tam, Peter; (Redwood City, CA), Wilson, Leland F.; (Menlo Park, CA) Correspondence: REED & ASSOCIATES; 800 MENLO AVENUE; SUITE 210; MENLO PARK; CA; 94025; US Patent Application Number: 20020161016 Date filed: November 21, 2001 Abstract: A method is provided for treatment of premature ejaculation by administration of an antidepressant drug selected from tricyclic antidepressants, tetracyclic antidepressants, MAO inhibitors, azaspirone antidepressants, and atypical non-SRI antidepressants. In a preferred embodiment, administration is on as "asneeded" basis, i.e., the drug is administered immediately or at most several hours prior to sexual activity. Pharmaceutical formulations and packaged kits are also provided. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/721,412, filed Nov. 21, 2001, the disclosure of which is hereby incorporated by reference. This invention relates generally to methods and pharmaceutical compositions for the treatment of premature ejaculation. More particularly, the invention relates to the use of tricyclic, tetracyclic, and other antidepressant drugs in such methods and compositions. Premature ejaculation is a debilitating yet common sexual dysfunction, and has been estimated to affect at least 30 to 40 percent of men at some point in their lives (Derogatis (1980) Med. Aspects Hum. Sexuality 14:1168-76; Frank et al. (1978) New Engl. J. Med. 299:111-115; Schein et al. (1988) Fam. Pract. Res. J. 7(3):122-134). The condition can lead to an inability to enter into or sustain relationships, can cause psychological damage to sufferers, and can also impair reproductive success. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Combination of growth hormone secretagogues and antidepressants Inventor(s): Busch, Frank Robert; (Gales Ferry, CT), Welch, Willard McKowan JR.; (Mystic, CT) Correspondence: Gregg C. Benson; Pfizer Inc.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020002137 Date filed: May 18, 2001 Abstract: This invention is directed to combinations comprising a growth hormone secretagogue, a prodrug thereof or a pharmaceutically acceptable salt of said growth hormone secretagogue or said prodrug and an antidepressant, a prodrug thereof or a pharmaceutically acceptable salt of said antidepressant or said prodrug and to pharmaceutical compositions and kits comprising such combinations. Antidepressants
140 Antidepressants
within the scope of this invention include norepinephrine reuptake inhibitors (e.g., secondary and tertiary amine tricyclics), selective sertraline reuptake inhibitors, agents which are combined norepinephrine/sertraline reuptake inhibitors, monoamine oxidase inhibitors and atypical antidepressants. This invention is also directed to methods of improving the physical and/or psychological condition of a patient undergoing a medical procedure, to methods of treating musculoskeletal frailty, to methods of treating congestive heart failure and to methods of attenuating protein catabolic response after a major operation comprising administering such a combination. In particular, this invention relates to such compositions and kits that improve the cardiac function, metabolism, muscle tone and/or mental state of patients undergoing a medical procedure. The compositions and kits of this invention are also useful in treating central nervous system disorders of patients undergoing a medical procedure. Excerpt(s): This application claims priority from the provisional application U.S. serial No. 60/207,017, filed on May 25, 2000, the benefit of which is hereby claimed under 37 C.F.R.sctn.1.78(a)(3). 3. Increased mobilization of free fatty acids and use of fatty acids for energy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Composition and method combining an antidepressant with an NMDA receptor antagonist, for treating neuropathic pain Inventor(s): Caruso, Frank S.; (Colts Neck, NJ) Correspondence: Peter G. Dilworth, Esq.; DILWORTH & BARRESE, LLP; 333 Earle Ovington Blvd.; Uniondale; NY; 11553; US Patent Application Number: 20020035105 Date filed: September 28, 2001 Abstract: The neuropathic pain alleviating effectiveness of an antidepressant is significantly potentiated by administering the antidepressant prior to, with or following the administration of a nontoxic NMDA receptor antagonist. Excerpt(s): This invention relates to a composition and method for alleviating neuropathic pain. More particularly, this invention is directed to such a composition and method in which an antidepressant is combined with a nontoxic antagonist, or blocker, for the N-methyl-D-aspartate (NMDA) receptor. Neuropathic pain is pain that is due to functional abnormalities of the nervous system. Fields, "Pain", McGraw-Hill, Inc. (1987), pp. 133 et seq. There are a variety of possible mechanisms by which nerve dysfunction can cause neuropathic pain: hyperactivity in primary afferent or central nervous system (CNS) nociceptive neurons, loss of central inhibitory connections, and increased activity in sympathetic efferents. Neuropathic pain typically occurs following injury to elements of the nervous system involved in nociception, such as peripheral nerve injury, in which the lesions deafferent the nociceptive pathway, the resultant pain sometimes being referred to deafferentation pain. Neuropathic pain is much more likely to occur with peripheral than with central nervous system damage. Examples of causes of painful nerve injury are: accidental trauma, tumors, cerval or lumbar spine disease, and surgical procedures. These injuries usually involve one or two peripheral nerves or nerve roots, and the pain is felt in the body region normally innervated by the damaged nerves. Additionally, there are also toxic, metabolic, and hereditary causes of painful polyneuropathies, erg., alcohol abuse, diabetes mellitus and toxicity due to cancer chemotherapy. These tend to be symmetrical and are most severe on the distal limbs.
Patents 141
U.S. Pat. No. 5,352,683 discloses a method for the treatment of chronic pain, inclusive of neuropathic pain, by administration of a nontoxic N-methyl-D-aspartate receptor antagonist such as dextromethorphan. However, there is no mention in this patent of combining a nontoxic NMDA receptor antagonist with an antidepressant for the treatment of neuropathic pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
COMPOSITIONS FOR THE TREATMENT OF PERIPHERAL NEUROPATHIES CONTAINING ANTIDEPRESSANTS AND/OR MONOAMINE OXIDASE INHIBITORS AND/OR VITAMIN B12 AND/OR PRECURSORS OR INDUCERS OF A NEUROTRANSMITTER Inventor(s): WORSLEY, ANDREW PETER; (FARNBOROUGH, GB) Correspondence: LARSON & TAYLOR; TRANSPOTOMAC PLAZA; 1199 NORTH FAIRFAX STREET; SUITE 900; ALEXANDRIA; VA; 22314 Patent Application Number: 20010008884 Date filed: March 4, 1999 Abstract: Methods and compositions for treatment of a patient suffering from a form of peripheral neuropathy are disclosed. The method comprises administering to the patient any one of the following combinations of components: I. A, B and C; II. A and B; III. B and C; IV. A and C, wherein A is an antidepressant or a monoamine oxidase inhibitor, B is vitamin B.sub.12, and C is a precursor or inducer of a neurotransmitter, e.g. Lphenylalanine. Excerpt(s): The present invention relates to the use of a combined medicament in the treatment of various forms of peripheral neuropathy, especially painful neuropathies and diabetic neuropathy, including diabetic amyotrophy, mononeuritis, mononeuritis multiplex, cranial nerve palsies and autonomic neuropathy. The invention also relates to the preparation of medicaments for such treatments. Diabetes mellitus is a metabolic disorder resulting in hyperglycaemia (raised blood sugar), polyuria (increased output of urine) and glycosuria (appearance of sugars (e.g. glucose) in the urine). Diabetes has been recognised as a major disease for centuries. In addition to defective carbohydrate metabolism, it can also lead to altered metabolism of lipids and proteins and patients are at risk of complications from microvascular and macrovascular diseases which are serious and may be fatal. Insulin dependent diabetes results from failure of the islets of Langerhans (.beta.) cells of the pancreas to produce sufficient insulin. This often arises as a result of auto-immunity directed against islet tissue. Non-insulin-dependent diabetes may in part arise from altered efficiency of insulin receptor signalling (insulin resistance) or from a relative deficiency of insulin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
142 Antidepressants
•
Controlled delivery of antidepressants Inventor(s): Ayer, Atul Devdatt; (Palo Alto, CA), Bhatt, Padmanabh; (Saratoga, CA), Cruz, Evangeline; (Hayward, CA), Yam, Noymi; (Sunnyvale, CA), Zhong, Adam; (Milpitas, CA) Correspondence: Robert R. Neller; ALZA Corporation; 1900 Charleston Road; P.O. Box 7210, M10-3; Mountain View; CA; 94039-7210; US Patent Application Number: 20010031279 Date filed: May 25, 2001 Abstract: Dosage forms and methods for the controlled release of antidepressives, such as exemplified by phenoxyethyl substituted-1,2,4-triazolones, over a prolonged period of time are described. Excerpt(s): This application claims the priority of provisional application No. 60/106,758, filed Nov. 2, 1998. This invention pertains to the controlled delivery of pharmaceutical agents and methods, dosage forms and devices therefor. In particular, the invention is directed to methods, dosage forms and devices for the controlled delivery of phenoxyethyl-substituted 1,2,4-triazolones that are useful as pharmaceutical agents, such as antidepressants, for example, nefazodone and nefazodone hydrochloride. Phenoxyethyl substituted-1,2,4-triazolones have been described as potent antidepressants in U.S. Pat. No. 4,338,317, which is incorporated herein by reference in its entirety. One of the most effective antidepressants in that group of compounds is nefazodone hydrochloride, sold under the trademark Serzone.RTM. by Bristol-Myers Squibb Co., and having the chemical name 2-[3-[4-(3-chlorophenyl)piperazinyl]propyl]-5-ethyl-4-(2-phenoxyethyl)-2H-1,2,4-triazol-3(4H)-one hydrochloride. Nefazodone hydrochloride and related compounds in the foregoing class of compounds, while rapidly absorbed, may be subject to extensive metabolism, resulting in low and variable bioavailability. For example, peak plasma concentrations for nefazodone hydrochloride occur at about one hour after dosing using conventional immediate release formulations and the half-life of nefazodone hydrochloride is on the order of 2-4 hours. The low bioavailability and short half-life of the aforementioned compounds results in the need for multiple daily dosing or dosing at drug levels that are high enough to obtain the desired anti-depressive effect, both of which may result in the occurrence of undesirable side effects in particular individuals under certain circumstances. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Gene expression profiling of antidepressant action in the brain Inventor(s): Bakker, Margot H.M.; ( Breda, NL), Bonaventure, Pascal; (San Diego, CA), Kamme, Fredrik; (San Diego, CA), Leysen, Josepha E.M.F.; (Oud-Turnhout, BE), Liu, Xuejun; (San Diego, CA), Meurers, Bernhard; (La Jolla, CA), Quo, Hongqing; (San Diego, CA) Correspondence: Philip S. Johnson, Esq.; Johnson & Johnson; One Johnson & Johnson Plaza; New Burnswick; NJ; 08933-7003; US Patent Application Number: 20020156038 Date filed: October 4, 2001
Patents 143
Abstract: Implementing gene expression to study drug action in the central nervous system is complicated by functional heterogeneity because of the existence of many different neuronal subtypes within the mammalian brain. The integration of laser capture microdissection (LCM) and RNA amplification with cDNA microarray technology allows for large-scale gene expression analysis at cellular level. Using this approach, we have generated gene expression profiles of imipramine, a reference antidepressant, and a new putative antidepressant, novelR1 in several laser-captured brain nuclei (locus coeruleus, dorsal raphe, hypothalamic paraventricular nucleus and hippocampus) of rats subjected to the chronic mild stress model (CMS) of depression. Excerpt(s): This application claims the benefit of United States Provisional Application Ser. No. 60/238,374, filed on Oct. 6, 2000, and U.S. Provisional Application Ser. No. 60/295,782, filed on Jun. 4, 2001. Microarray technology represents a potentially powerful approach to identifying genes specifically expressed in different cell of tissue type [P. O. Brown and D. Botstein, "Exploring the new world of the genome with DNA Microarrays" (1999) Nat Genet, 21:33-7; D. Shalon, "Gene expression micro-arrays: a new tool for genomic research", (1998) Pathol. Biol. (Paris), 46;107-9; S. M. Welford, J. Gregg, E. Chen, D. Garrison, P. H. Sorensen, C. T. Denny and S. F. Nelson, "Detection of differentially expressed genes in primary tumor tissues using representational differences analysis coupled to microarray hybridization" (1998) Nucleic Acids Res, 26:3059-65]. The application of microarray to the study of gene expression patterns in the central nervous system is complicated by functional heterogeneity because of the existence of many different neuronal subtypes within the mammalian brain [D. H. Geschwind, "Mice, microarrays, and the genetic diversity of the brain [In Process Citation]" (2000) Proc. Natl. Acad. Sci. USA, 97:10676-8; S. J. Watson, F. Meng, R. C. Thompson and H. Akil, "The `chip` as a specific genetic tool" (2000) Biol Psychiatry, 48:1147-56]. This heterogeneity consists of literally hundreds of brain nuclei that are in close proximity to each other as well as many different neuronal subtypes in cortical layers of different brain regions. We have demonstrated in a previous study that the integration of laser capture microdissection (LCM), T7 based RNA amplification and cDNA microarrays allows to profile gene expression at cellular level [L. Luo, R. C. Salunga, H. Guo, A. Bittner, K. C. Joy, J. E. Galindo, H. Xiao, K. E. Rogers, J. Wan, M. R. Jackson and M. G. Erlander, "Gene expression profiles of laser-captured adjacent neuronal subtypes" (1999) [published erratum appears in Nat Med 1999 Mar; 5(3):355], Nat Med, 5:117-22.; R. C. Salunga, H. Guo, L. Luo, A. Bittner, K. C. Joy, J. Chambers, J. Wan, M. R. Jackson and M. G. Erlander, "Gene expression analysis via cDNA microarrays of laser capture microdissected cells from fixed tissue" (1999) In M. Schena (Ed.), "DNA microarrays a practical approach", Oxford University Press, Oxford]. Panel B: hippocampus after capture of CA1 cells (c) CA1 captured cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Individualization of therapy with antidepressants Inventor(s): Leyland-Jones, Brian; (Miami, FL) Correspondence: HAMILTON, BROOK, SMITH & REYNOLDS, P.C.; 530 VIRGINIA ROAD; P.O. BOX 9133; CONCORD; MA; 01742-9133; US Patent Application Number: 20030072710 Date filed: March 14, 2002 Abstract: The invention relates to the individualization of therapy on the basis of a phenotypic profile of an individual. More specifically, the present invention relates to
144 Antidepressants
the use of metabolic phenotyping for the individualization of treatment with antidepressants. Excerpt(s): This application is a new application which claims the benefit of U.S. Provisional Application No. 60/275,490, filed on Mar. 14, 2001. The entire teachings of the above application is incorporated herein by reference. The invention relates to a system and method for individualization of therapy with antidepressants. More specifically, the present invention relates to the use of metabolic phenotyping in individualizing treatment with antidepressants. For the majority of drugs (or xenobiotics) administered to humans, their fate is to be metabolized in the liver, into a form less toxic and lipophilic with their subsequent excretion in the urine. Their metabolism involves two systems (Phase I and Phase II) which act consecutively: Phase I enzymes include the cytochrome P450 system which includes at least 20 enzymes catalyzing oxidation reactions as well as carboxylesterase, amindases, epoxide hydrolase, quinine reductase, alcohol and aldehyde dehydrogenase, xanthine oxidase and flavin-containing monooxygenase. These enzymes are localized in the microsomal fraction. Phase II enzymes include the conjugation system which involves at least 5 enzymes including, N-acetyltransferases (NAT), UDP-glucoronyltransferases (UGT), sulfotransferases (SUT), and glutathione-S-transferases (GST). A detailed description of the complex human drug metabolizing systems is provided in Kumar and Surapaneni (Medicinal Res. Rev. (2001) 21(5):397-411) and patent application WO 01/59127 A2. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Long acting antidepressant microparticles Inventor(s): Mulchahey, Jeffrey; (Hamilton, OH), Zemlan, Frank P.; (Cincinnati, OH) Correspondence: Frost Brown Todd LLC; 2200 PNC Center; 201 East Fifth Street; Cincinnati; OH; 45202; US Patent Application Number: 20020132854 Date filed: August 30, 2001 Abstract: Pharmaceutically-active materials comprising specific antidepressant compounds, such as sertraline, contained in microparticles formulated so as to release the antidepressant compounds over an extended period of time are disclosed. The materials, when administered, particularly by injection, release the active agent over time allowing the patient to be effectively treated without requiring multiple dosing of the pharmaceutical material. Pharmaceutical compositions containing the microparticles and methods of treating depression-related conditions utilizing the microparticles are also disclosed. Excerpt(s): This application is based on and claims priority from U.S. Provisional Application Serial No. 60/234,434, filed Sep. 21, 2000. The present invention relates to pharmaceutically-active compositions, particularly injectable compositions, which provide long-acting antidepressant activity. Mood and anxiety disorders, in their various forms and combinations, constitute a major source of personal suffering and impaired ability to engage in productive work and interpersonal relationships in the United States today. Between five and nine percent of women, and between two and three percent of men meet the diagnostic criteria for major depression at any time; ten to twenty-five percent of all women suffer major depression at some point in their lives, while five to ten percent of men will develop a major depressive disorder (American Psychiatric Association, 1994). Anxiety disorders, e.g., obsessive-compulsive disorder
Patents 145
(OCD), post-traumatic stress disorder (PTSD), panic disorder and generalized anxiety disorder (GAD), show lifetime prevalence rates of approximately 2.5%, 7%, 2.5% and 5%, respectively. Between 3% and 13% of individuals in community samples are regarded as meeting the diagnostic criteria for social phobia. Mood and anxiety disorders are common co-morbidities (American Psychiatric Association, 1994), and the most common antidepressant medications, including serotonin re-uptake inhibitors, mixed serotonin-catecholamine re-uptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors--are all effective treatments for anxiety and panic attacks. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Marker for antidepressant therapy and methods related thereto Inventor(s): Donati, Robert J.; (Chicago, IL), Rasenick, Mark M.; (Glenview, IL), Toki, Sadamu; (Sapporo, JP) Correspondence: MARSHALL, O'TOOLE, GERSTEIN, MURRAY & BORUN; 6300 SEARS TOWER; 233 SOUTH WACKER DRIVE; CHICAGO; IL; 60606-6402; US Patent Application Number: 20020039752 Date filed: July 30, 2001 Abstract: The present invention relates generally to methods for determining the effectiveness of ongoing antidepressant therapy via analysis of the association of G.sub.s.alpha. with components of the plasma membrane or cytoskeleton of cells from peripheral tissues of the depressed individual as well as to methods involved in screening for effective antidepressant agents via their ability to cause a difference in the association of G.sub.s.alpha. with components of the plasma membrane or cytoskeleton of cells. Excerpt(s): Priority is claimed to U.S. Provisional Appl. No. 60/221,874, filed Jul. 29, 2000, which is incorporated herein by reference in its entirety. This invention relates generally to methods for determining the effectiveness of antidepressant therapy in a depressed individual as well as methods for detecting agents that possess antidepressant activity. Affective disorders are characterized by changes in mood as the primary clinical manifestation. Major depression is one of the most common mental illnesses and is often under diagnosed and frequently undertreated, or treated inappropriately. Major depression is characterized by feelings of intense sadness and despair, mental slowing and loss of concentration, pessimistic worry, agitation, and selfdeprecation. Physical changes usually occur that include insomnia, anorexia and weight loss (or overeating) decreased energy and libido, and disruption of the normal circadian rhythms of activity, body temperature, and many endocrine functions. As many as 1015% of individuals with this disorder display suicidal behavior during their lifetime. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
146 Antidepressants
•
Method of controlling weight gain associated with therapeutic drugs Inventor(s): Mendel, Carl M.; (Short Hills, NJ), Seaton, Timothy B.; (Far Hills, NJ), Weinstein, Steve P.; (Hartsdale, NY) Correspondence: JOHN D. CONWAY; ABBOTT BIORESEARCH CENTER; 100 RESEARCH DRIVE; WORCESTER; MA; 01605-4314; US Patent Application Number: 20030008897 Date filed: March 17, 2000 Abstract: A compound of formula I 1or a pharmaceutically acceptable salt thereof in which R.sub.1 and R.sub.2 are independently H or methyl (for example N,N-dimethyl-1[1-(4-chlorophe- nyl)cyclobutyl]-3-methylbutyl amine hydrochloride optionally in the form of its monohydrate) is used for treating weight gain associated with treatment with certain drug therapy, including the use of tricyclic antidepressants, lithium, sulphonylureas, beta-adrenergic blockers, certain steroid contraceptives, corticosteroids, insulin, cyproheptadine, sodium valproate, neuroleptics, phenothiazine or piztifen. Excerpt(s): This invention relates to a method of controlling weight gain associated with treatment with medicines. including enantiomers and pharmaceutically acceptable salts thereof, in which R.sub.1 and R.sub.2 are independently H or methyl, is administered in conjunction with a pharmaceutically acceptable diluent or carrier to a human in need thereof. The use of certain therapeutic drugs can promote weight gain. These drugs include tricyclic antidepressants, lithium, sulphonylureas, beta-adrenergic blockers, certain steroid contraceptives, corticosteroids, insulin, cyproheptadine, sodium valproate, piztifen, neuroleptics including typical neuroleptics for example phenothiazine and phenothiazine derivatives such as chlorpromazine, thioridazine, fluphenazine and trifluoperazine; butyrophenones such as haloperidol; thioxanthenes such as flupentixol and substituted benzamides such as sulpiride, atypical neuroleptics including clozapine, olanzapine, zotepine, risperidone, quetiapine and ziprasidone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Novel compounds for use as antidepressants, aphrodisiacs and adjunctive therapies in humans Inventor(s): Berger, Patricia J.; (Cora, WY), Negus, Norman C.; (Cora, WY), Rosenfeld, Mark J.; (Salt Lake City, UT) Correspondence: MALLINCKRODT & MALLINCKRODT; 10 EXCHANGE PLACE, SUITE 510; SALT LAKE CITY; UT; 84111; US Patent Application Number: 20010053789 Date filed: April 13, 2001 Abstract: Phenolic compounds with a phenolic molecule to which are covalently linked an oxygen-containing group, a nitrogen- or another oxygen containing group, and a C.sub.1-C.sub.4 alkoxy group, obtainable from monocotyledonous plants, animals that eat such plants, or chemical synthesis, have been found to act as an antidepressant or otherwise a treatment for bettering mood, a therapy for improving sexual desire or performance, an adjunctive therapy for achieving weight loss, and an adjunctive therapy for substance abuse and addiction. These compounds, at concentrations suitable for human therapeutic use, may be obtained from plants such as corn in their early growth stages and from parts of animals such as the velvet antler tips of deer and elk.
Patents 147
Excerpt(s): The invention is in the field of treating depression, sexual dysfunction, substance abuse or addiction, and in inducing weight loss, compounds used in such treatments, and the making of such compounds. An estimated 35-40 million living Americans will suffer major depressive episodes, and many more will experience lesser bouts. Of the approximately 17.5 million Americans with ongoing depressions, about 9.2 million are at a clinically debilitating level. Clinical depression is characterized by a list of symptoms that last over a long time span. It is a serious problem that is usually or initially caused by outside stressors. As stresses escalate or persist, a chemical imbalance can result. Clinical depression can be very debilitating both physically and mentally and even lead to death by means of suicide. However, lost productivity and relationship problems are also consequences of lesser depressions. At present, antidepressant medications are the cornerstones of treating depression, especially those that are at least moderately severe. Although depressed people tend to improve when treated with antidepressants, many do not respond to the first one. Such individuals may eventually benefit from a different antidepressant or a combination of antidepressants. Sexual dysfunction is a pervasive disorder. In the overall population, 43 percent of women and 31 percent of men between the ages of 18 and 59 repeatedly experience it. Sexual dysfunction includes lacking interest in sex, problems with arousal, not enjoying sex, and anxiety about sexual performance. Indeed, feeling good in general has significant impact on sexual function, with those people unhappy or depressed more likely to experience difficulties. Arousal problems affect over 20 million American males, about two in 10 adult men, with such difficulties often associated with or accompanied by some sort of depression. Meanwhile, prescription antidepressants actually exacerbate the situation, since a frequent side effect of their use is sexual dysfunction. In fact, sexual response diminishes in up to 75% of prescription antidepressant users. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical composition for treatment of acute, chronic pain and/or neuropathic pain and migraines Inventor(s): Coe, Jotham W.; (Niantic, CT), Harrigan, Edmund P.; (Old Lyme, CT), O'Neill, Brian T.; (Old Saybrook, CT), Sands, Steven B.; (Stonington, CT), Watsky, Eric J.; (Stonington, CT) Correspondence: Paul H. Ginsburg; Pfizer Inc; 20th Floor; 235 East 42nd Street; New York; NY; 10017-5755; US Patent Application Number: 20010036943 Date filed: December 18, 2000 Abstract: Pharmaceutical compositions are disclosed for the treatment of acute, chronic and/or neuropathic pain. The pharmaceutical compositions are comprised of a therapeutically effective combination of a nicotine receptor partial agonist and an analgesic agent and a pharmaceutically acceptable carrier. The analgesic agent is selected from opioid analgesics, NMDA antagonists, substance P antagonists, COX 1 and COX 2 inhibitors , tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), capsaicin receptor agonists, anesthetic agents, benzodiazepines, skeletal muscle relaxants, migraine therapeutic agents, anti-convulsants, antihypertensives, anti-arrythmics, antihistamines, steroids, caffeine, and botulinum toxin. The method of using these compounds and a method of treating acute, chronic and/or neuropathic pain and migraine in a mammal including a human is also disclosed.
148 Antidepressants
Excerpt(s): The present invention relates to pharmaceutical compositions for the treatment of acute, chronic and/or neuropathic pain and migraine in a mammal (e.g. human) comprising a nicotine receptor partial agonist (NRPA) and analgesic agents, including opioid analgesics, NMDA antagonists, substance P antagonists, COX 1 and COX 2 inhibitors , tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), capsaicin receptor agonists, anesthetic agents, benzodiazepines, skeletal muscle relaxants, migraine therapeutic agents, anti-convulsants, antihypertensives, anti-arrythmics, antihistamines, steroids, caffeine, N-type calcium channel antagonists and botulinum toxin. The term NRPA refers to all chemical compounds which bind at neuronal nicotinic acetylcholine specific receptor sites in mammalian tissue and elicit a partial agonist response. A partial agonist response is defined here to mean a partial, or incomplete functional effect in a given functional assay. Additionally, a partial agonist will also exhibit some degree of antagonist activity by its ability to block the action of a full agonist (Feldman, R. S., Meyer, J. S. & Quenzer, L. F. Principles of Neuropsychopharmacology, 1997; Sinauer Assoc. Inc.). The present invention may be used to treat mammals (e.g. humans) for acute, chronic and/or neuropathic pain with a decrease in the severity of unwanted side effects such as causing nausea and/or stomach upset. The invention also relates to aryl fused azapolycylic compounds that bind to neuronal nicotinic acetylcholine specific receptor sites and are useful in modulating cholinergic function and are referred to in WO 9818798-A1, WO 9935131-A1 and WO 9955680-A1. The foregoing applications are owned in common with the present application and are incorporated herein by reference in their entireties. Analgesic agents decrease pain perception. In animal models of pain states, the above compounds inhibit acute pain perception. These compounds also inhibit pain sensitization processes in which the perception of the painfulness of a given stimulus is increased without any change in stimulus intensity. In humans, analgesic agents have also been found to decrease both acute pain perception and sensitization. Opioid analgesic agents, in particular, remain the most effective means of alleviating severe pain across a broad spectrum, including inflammatory as well as neuropathic pain states. However, even though analgesic agents have therapeutic utility in the treatment of pain, there are significant liabilities to the use of analgesic compounds. Specifically, many of these compounds that have been tested in humans can cause potentially serious side effects such as gastrointestinal complications including nausea, emesis, ulcers, and constipation, respiratory depression, and psychological and physical dependence. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Phenoxypropylamine compounds Inventor(s): Bougauchi, Masahiro; (Tokyo, JP), Kanzaki, Kouji; (Tokyo, JP), Kuroita, Takanobu; (Tokyo, JP), Minoguchi, Masanori; (Tokyo, JP), Morio, Yasunori; (Tokyo, JP), Nishiyama, Akira; (Tokyo, JP) Correspondence: WENDEROTH, LIND & PONACK, L.L.P.; 2033 K STREET N. W.; SUITE 800; WASHINGTON; DC; 20006-1021; US Patent Application Number: 20020111358 Date filed: November 23, 2001 Abstract: The present invention relates to a phenoxypropylamine compound of the formula (I) 1wherein each symbol is as defined in the specification, an optically active compound thereof or a pharmaceutically acceptable salt thereof and hydrates thereof,
Patents 149
which simultaneously show selective affinity for and antagonistic activity against 5HT.sub.1A receptor, as well as 5-HT reuptake inhibitory activity, and can be used as antidepressants quick in expressing an anti-depressive effect. Excerpt(s): This is a continuation in part of PCT/JP00/03279 filed on May 22, 2000. The present invention relates to a compound that acts on 5-hydroxytryptamine (5-HT) neurotransmission. More particularly, the present invention relates to a novel phenoxypropylamine compound having selective affinity for and simultaneous antagonistic activity against a 5-hydroxytryptamine 1A (5-HT.sub.1A) receptor in the central nervous system, as well as a 5-HT reuptake inhibitory activity, which is useful as a pharmaceutical agent, and to a therapeutic agent for depression and the like, which contains this compound. 5-Hydroxytryptamine (5-HT) is also known as "serotonin". As a compound having an antagonistic activity against 5-HT.sub.1A receptor as well as an inhibitory activity on the reuptake of 5-HT, there are known, for example, 1-(4indolyloxy)-3-(4-(3,4-methylenedioxyphenyl)p- iperidino)-2-propanol derivative (EP 0722941), 4-(4-fluorophenyl)-1-((6-(methylamino)indan-1-yl)methyl)piperidine derivative (WO 95/33721), 3,6-dihydro-N-methyl-N-(5-chloro-2-pyridyl)-4--(1naphthalenyl)-1-(2H)pyr- idine propanamine derivative (U.S. Pat. No. 5472966), 3-(5chlorobenzo[b]thiophen-3-yl)-5,6-dihydroimidazo[2,1-b]thiazol derivative (WO 97/02269), S-(-)-N-(2-(3-(2-naphthyl)-pyrrolidino)ethyl)-N-(2pyridyl)cyclohexanecarboxamide derivative (WO 97/40038), (R)-3-(N-cyclopentyl-N-npropylamino)-8-fluoro-5-(N-methylcarbamoyl)-3,4-dihydro-2H-1-benzopyran derivative (WO 96/33710), 3-(2-(4-methylpiperazin-1-yl)benzylidene)-1,3dihydroindol-2-one derivative (WO 97/36867), (S)-1-(4-indolyloxy)-3-[4-hydroxy-4-(2naphthyl)piperidino]-propan-2-ol derivative (WO 97/48698) and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for preparing a piperidine derivative Inventor(s): Igi, Masami; (Osaka, JP), Ishibashi, Taro; (Osaka, JP), Itaya, Nobushige; (Osaka, JP), Katsura, Tadashi; (Osaka, JP), Kawada, Yoshihiro; (Osaka, JP), Sugi, Kiyoshi; (Osaka, JP), Tagami, Yayoi; (Osaka, JP), Yamaoka, Teiji; (Osaka, JP), Yamazaki, Shigeya; (Osaka, JP) Correspondence: BIRCH STEWART KOLASCH & BIRCH; PO BOX 747; FALLS CHURCH; VA; 22040-0747; US Patent Application Number: 20030144519 Date filed: January 6, 2003 Abstract: A piperidine derivative, which can be used as an intermediate for pharmaceuticals such as paroxetine useful as antidepressants, represented by the general formula (I): 1wherein R.sup.1 is hydrogen atom, benzyloxycarbonyl group or tert-butoxycarbonyl group; R.sup.2 is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position, (3,4-methylenedioxyphenyl)oxymethyl group, carboxyl group or --CO.sub.2R.sup.7 group in which R.sup.7 is an alkyl group having 1 to 5 carbon atoms, and Z is methylene group or carbonyl group, with proviso that, (A) when R.sup.1 is benzyloxycarbonyl group or tert-butoxycarbonyl group, then R.sup.2 is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position or (3,4-methylenedioxyphenyl)oxymethyl group, and Z is methylene group; or (B) when R.sup.1 is hydrogen atom and Z is carbonyl group, then
150 Antidepressants
R.sup.2 is carboxyl group or --CO.sub.2R.sup.7 group (R.sup.7 is as defined above); or (C) when R.sup.1 is hydrogen atom and Z is methylene group, then R.sup.2 is hydroxymethyl group Excerpt(s): The present invention relates to a piperidine derivative and a process for preparing the same More particularly, the present invention relates to a piperidine derivative useful as an intermediate for pharmaceuticals such as paroxetine and the like which are useful, for example, as an antidepressant. In general, paroxetine useful as an antidepressant is prepared by the processes described, for example, in Japanese Unexamined Patent Publication No. 7-138228 and Japanese Examined Patent Publication No. 59-46216. However, these processes have the drawback that, upon deprotection of N-methyl group, complicated procedures such as hydrolysis after the transformation of N-methyl group to carbamate group are required. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Transdermal and topical administration of antidepressant drugs using basic enhancers Inventor(s): Hickey, Alan T. J.; (San Diego, CA), Hsu, Tsung-Min; (San Diego, CA), Luo, Eric C.; (Plano, TX), Obara, Jane; (San Diego, CA) Correspondence: REED & ASSOCIATES; 800 MENLO AVENUE; SUITE 210; MENLO PARK; CA; 94025; US Patent Application Number: 20020192302 Date filed: June 19, 2002 Abstract: Methods are provided for enhancing the permeability of skin or mucosal tissue to topical or transdermal application of antidepressant drugs. The methods entail the use of a base in order to increase the flux of the drug through a body surface while minimizing the likelihood of skin damage, irritation or sensitization. The permeation enhancer can be an inorganic or organic base. Compositions and transdermal systems are also described. Excerpt(s): This application is a continuation in part of U.S. Ser. No. 09/972,008 filed on Oct. 4, 2001, which is a continuation in part of U.S. Ser. No. 09/738,410 filed on Dec. 14, 2000, which is a continuation in part of U.S. Ser. No. 09/569,889 filed on May 11, 2000, which is a continuation in part of U.S. Ser. No. 09/465,098 filed on Dec. 16, 1999; and is a continuation in part of U.S. Ser. No. 09/738,395 filed on Dec. 14, 2000, which is a continuation in part of U.S. Ser. No. 09/607,892 filed on Jun. 30, 2000, now abandoned. This invention relates generally to the topical and transdermal administration of antidepressant drugs, and more particularly relates to methods and compositions for enhancing the flux of antidepressant drugs through a body surface utilizing a basic permeation enhancer. The delivery of drugs through the skin provides many advantages; primarily, such a means of delivery is a comfortable, convenient and noninvasive way of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences, e.g., gastrointestinal irritation and the like, are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 151
•
Tricyclic antidepressants and their analogues as long-acting local anesthetics and analgesics Inventor(s): Gerner, Peter; (Weston, MA), Wang, Ging Kuo; (Westwood, MA) Correspondence: Edward R. Gates, Esq.; Wolf, Greenfield & Sacks, P.C.; 600 Atlantic Avenue; Boston; MA; 02210; US Patent Application Number: 20020094975 Date filed: September 26, 2001 Abstract: Methods and compositions of tricyclic antidepressants for inducing local longlasting anesthesia and analgesia are provided. The methods and compositions are useful for alleviating acute and chronic pain, particularly useful for treating a localized pain. Excerpt(s): This invention relates to the use of the tricyclic antidepressants to produce local long-acting relief of different varieties of pain. To provide a better understanding of the invention it is necessary to distinguish between the two terms analgesia and anesthesia. Analgesia is defined as a condition in which nociceptive stimuli are sensed but are not interpreted as pain. Anesthesia is a state characterized by total loss of sensation, the result of pharmacologic depression of nerve function. Thus, analgesia does not produce anesthesia whereas anesthesia produces analgesia. In general, pain is associated with a known tissue pathology (e.g., cancer pain, arthritic pain), inflammation, or injury to a body tissue (e.g., surgery). Neuropathic pain is thought to be a consequence of damage to peripheral nerves or to regions of the central nervous system. Neuropathic pain can present as an acute pain but frequently occurs as a form of chronic pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Use of a NK-1 receptor antagonist and an antidepressant and/or an anti-anxiety agent Inventor(s): Carlson, Emma Joanne; (Puckeridge, GB), Rupniak, Nadia Melanie; (Bishops Stortford, GB) Correspondence: MERCK AND CO INC; P O BOX 2000; RAHWAY; NJ; 070650907 Patent Application Number: 20020042361 Date filed: October 16, 2001 Abstract: The present invention relates to the treatment or prevention of depression and/or anxiety by the administration of a combination of a specific class of NK-1 receptor antagonists and an antidepressant or anti-anxiety agent. The present invention also provides preclinical screens for anxiolytic and antidepressant activity of NK-1 receptor antagonists. Excerpt(s): This invention relates to the treatment or prevention of depression and/or anxiety by the administration of a combination of a specific class of NK-1 receptor antagonists and an antidepressant or anti-anxiety agent. The present invention also provides preclinical screens for anxiolytic and antidepressant activity of NK-1 receptor antagonists. Major depression is characterised by feelings of intense sadness and despair, mental slowing and loss of concentration, pessimistic worry, agitation, and selfdeprecation. Physical changes also occur, especially in severe or "melancholic" depression. These include insomnia or hypersomnia, anorexia and weight loss (or sometimes overeating), decreased energy and libido, and disruption of normal circadian rhythms of activity, body temperature, and many endocrine functions. Treatment
152 Antidepressants
regimens commonly include the use of tricyclic antidepressants, monoamine oxidase inhibitors, some psychotropic drugs, lithium carbonate, and electroconvulsive therapy (ECT) (see R. J. Baldessarini in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Edition, Chapter 19, McGraw-Hill, 1996 for a review). More recently, new classes of antidepressant drugs are being developed including selective serotonin reuptake inhibitors (SSRIs), specific monoamine reuptake inhibitors and 5-HT.sub.1A receptor agonists, antagonists and partial agonists. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of sulodexide for the treatment of inflammatory bowel disease Inventor(s): Laster, Morris; (Jerusalem, IL), Shelach, Noa; (Jerusalem, IL), Spero, Michael; (Jerusalem, IL) Correspondence: PENNIE AND EDMONDS; 1155 AVENUE OF THE AMERICAS; NEW YORK; NY; 100362711 Patent Application Number: 20030008844 Date filed: May 16, 2002 Abstract: The present invention is directed to methods for preventing or treating inflammatory bowel disease by administering a composition comprising a therapeutically or prophylactically effective amount of a composition comprising between about 60% to 90% iduronylglycosaminoglycan sulfate and between about 10% to 40% dermatan sulfate, or a pharmaceutically acceptable salt, solvate, hydrate, or clathrate thereof. In a particular embodiment, a therapeutically or prophylactically effective amount of a composition comprising sulodexide, or a pharmaceutically acceptable salt, solvate, hydrate, or clathrate thereof is administered. The composition to be administered may also comprise one or more additional active ingredients selected from the group consisting of steroids, aminosalicylates, short-chain fatty acids, thioguanine derivatives, antibiotics, biological agents, antidepressants, and painrelievers. Excerpt(s): The present invention claims priority benefits of U.S. Provisional Application Serial No. 60/291,667 filed May 17, 2001, the disclosure of which is incorporated herein by reference in its entirety. The present invention relates to methods of preventing and treating inflammatory bowel disease. Inflammatory Bowel Disease (IBD) is a chronic recurrent inflammatory disease that affects either or both the small intestine and the colon. IBD comprises two major groups: Crohn's disease and ulcerative colitis. The disease affects the small intestine, colon, or both. IBD's cause(s) are not known, but a number of theories have been put forward. Genetic, infectious, immunologic, and even psychological factors have been implicated in a number of studies. For example, 15 to 30 percent of patients have at least one relative that also has IBD. Also, the immune system of patients with IBD have been shown to undergo many changes. Research are being done to determine if a specific gene or group of genes make a person more susceptible to the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 153
•
Utilization of an egg-based preparation as an antidepressant Inventor(s): Eskeland, Bjodne; (Oslo, NO) Correspondence: YOUNG & THOMPSON; 745 SOUTH 23RD STREET 2ND FLOOR; ARLINGTON; VA; 22202 Patent Application Number: 20010033869 Date filed: May 29, 2001 Abstract: The utilization of an egg-based preparation as an antidepressant. Excerpt(s): The present invention relates to the use of an egg-based preparation as an antidepressant. More specifically, the invention relates to the utilization of a preparation corresponding to the one described in NO 922988 and the WO 94/03192 based thereon, as an antidepressant. In NO application 922988 there is described a potency enhancing agent based on a powder produced from fertilized avian eggs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with antidepressants, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “antidepressants” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on antidepressants. You can also use this procedure to view pending patent applications concerning antidepressants. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
155
CHAPTER 7. BOOKS ON ANTIDEPRESSANTS Overview This chapter provides bibliographic book references relating to antidepressants. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on antidepressants include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “antidepressants” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on antidepressants: •
101 Medication Tips for People with Diabetes Source: Alexandria, VA: American Diabetes Association. 1999. 122 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $14.95 plus shipping and handling. ISBN: 1580400329. Order number 483301. Summary: This book answers 101 of the most commonly asked questions about diabetes and medications to help readers become active members of their health care team, maximize their diabetes management, and stay well. Questions in chapter one provide general information on medications used to treat diabetes. Chapter two focuses on how to get the most out of oral medications. The third chapter deals with common side effects of oral medications, including gastrointestinal and liver problems, weight gain,
156 Antidepressants
lactic acidosis, and hypoglycemia. Questions in chapter four provide general information on the use of insulin in type 2 diabetes. This is followed by a chapter that explains how to get the most out of insulin therapy. Chapter six identifies the common side effects of insulin, including weight gain. Questions in the next chapter deal with the meditations used to treat complications, including nonprescription analgesics, tricyclic antidepressants, capsaicin cream, angiotensin converting enzyme inhibitors, laxatives, and calcium channel blockers. This is followed by chapters that answer questions about the effect of medications on diabetes; the use of nonprescription medications such as aspirin, cold and allergy medications, herbal supplements, weight loss products, and vitamin and mineral supplements; and common drug interactions that occur with diabetes medications. The final chapter answers miscellaneous questions. The book also includes a glossary and an index. •
Interface Between Dementia and Depression Source: London, England: Martin Dunitz, Ltd. 1999. 58 p. Contact: Available from Martin Dunitz, Ltd. The Livery House, 7-9 Pratt Street, London NW1 0AE, ENGLAND. +44 020 7482 2202; FAX: +44 020 7267 0159. Internet: http://www.dunitz.co.uk. PRICE: 9.95 British pounds. ISBN: 1853176583. Summary: This book discusses the diagnosis and treatment of elderly patients with symptoms of both depression and dementia. The first section reviews the epidemiology of late-life depression and dementia. The second section addresses the clinical assessment of mixed depressive and cognitive states. It reviews tools and diagnotic criteria used to assess depression and dementia. The third section focuses on the depressed patient with cognitive impairment. It reviews research findings on the effectiveness of selected treatments for depression. The fourth section looks at treatment of depression in patients with dementia, including antidepressants and cognitive enhancers. The final section reviews the neurobiology of late-life depression and dementia, and examines theoretical models of the interface between the two disorders. Includes references.
•
Oral Disease: Colour Guide. 2nd ed Source: Edinburgh, Scotland: Churchill Livingstone. 1999. 174 p. Contact: Available from W.B. Saunders Company, A Harcourt Health Sciences Company. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St Louis, MO 63146-9988. (800) 545-2522. Fax (800) 568-5136. E-mail:
[email protected]. Website: www.wbsaunders.com. PRICE: $19.95 plus shipping and handling. ISBN: 044306170X. Summary: This book is intended as an aid to oral medicine and the diagnosis and treatment of oral disease. The format describes diseases initially by site, as this is how patients present. The text and illustrations (full color photographs) cover the common conditions seen in oral medicine, and some of the less common and exotic. Photographs and descriptions are offered in 12 chapters: lip lesions, intraoral lesions (mucosal ulcers), intraoral white lesions, intraoral colored or pigmented lesions, intraoral lumps, tongue lesions, gingival lesions, major salivary gland disease, cervical lymph node swellings, neurological disorders, teeth disorders, and HIV disease. An appendix lists common drug therapies used for oral diseases, including dosages and contraindications for analgesics, anxiolytics, corticosteroids, systemic immunosuppressants, antifungals, antivirals, antidepressants. The handbook concludes with a subject index.
Books
•
157
Chronic Fatigue and Related Immune Deficiency Syndromes Contact: American Psychiatric Press, Inc., 1400 K St NW, Washington, DC, 20005, (800) 368-5777. Summary: This book presents a synthesis of the research into disorders of chronic fatigue. The contributing authors examine the relationship between chronic fatigue and immune deficiency syndromes and major biological depression. This includes a discussion of their cause, psychopathology, neuroendocrinology, neurochemistry, and treatment. The papers consider the immunological correlates, viral etiology, neuroendocrine research, and psychological and cognitive aspects of chronic fatigue syndrome. The chapters on treatment review current treatment approaches and set the scene for future developments in antivirals and antidepressants.
•
Psychopharmacological Treatment Complications in the Elderly Source: Washington, DC: American Psychiatric Press, Inc. 1992. 126 p. Contact: Available from American Psychiatric Press, Inc. 1400 K Street, NW, Washington, DC 20005. (202) 682-6262. PRICE: $23.00. Summary: This book presents research findings on side effects and other complications associated with psychotropic drug treatment in the elderly, including persons with Alzheimer's disease. The book is intended to help mental health clinicians evaluate riskbenefit ratios for psychotropic drug use and select appropriate alternative treatment approaches. The clinical situations described are those frequently encountered in the treatment of mental illness in older patients who concomitantly experience other medical problems. Six chapters address the following topics: adverse cognitive effects of tricyclic antidepressants in the treatment of geriatric depression; cardiac risks of antidepressants in the elderly; neurological side effects of psychotropic medications in the elderly; neuroleptic malignant syndrome in the elderly; problems associated with long term benzodiazepine use in the elderly; and efficacy and side effects of cholinergic drugs used in the treatment of Alzheimer's disease. References are included at the end of each chapter.
•
Mayo Clinic on Arthritis Source: Rochester, MN: Mayo Clinic. 1999. 202 p. Contact: Available from Mayo Clinic, Health Information Division, 200 First Street SW, 5th Floor Centerplace Building, Rochester, MN 55905. (800) 291-1128 ext. 250. PRICE: $14.95 plus shipping and handling. ISBN 1893005003. Summary: This book provides people who have arthritis with practical, easy to understand information on osteoarthritis and rheumatoid arthritis. The contents are based on the self-help approach that Mayo Clinic practitioners take with those seeking health care at this facility. The book begins with a chapter describing common forms of arthritis, other arthritic disorders, and related musculoskeletal conditions. This is followed by a chapter that explains the fundamental principles of joint protection and offers tips on using various assistive devices. Other chapters provide guidelines on exercising properly, controlling pain, eating for better health, and gaining control over arthritis and enhancing quality of life. The book continues with a chapter on the effectiveness and side effects of nonsteroidal anti-inflammatory drugs, corticosteroids, disease-modifying antirheumatic drugs, immunosuppressants, pain reducers, antidepressants, muscle relaxants, tranquilizers, and hyaluronate injections. The next chapter explains how surgery can help hand and wrist joints, shoulders, hips, knees,
158 Antidepressants
and ankles and feet. This is followed by a chapter on alternative treatments. Topics include types of treatment available and the evaluation of alternative methods. Another chapter reports on promising trends in arthritis research and new diagnostic tools, medications, lifestyle approaches, operations, and other treatments under study. The remaining chapters offer suggestions on traveling with arthritis, discuss job-related issues, and identify sources of help. 59 figures. •
Behavioral Disorders in Dementia: Agitation, Aggression, and Psychosis: What the Clinician Needs to Know Source: Bethesda, MD: American Association for Geriatric Psychiatry. 1998. 20 p. Contact: Available from American Association for Geriatric Psychiatry. 7910 Woodmont Avenue, Suite 1050, Bethesda, MD 20814. (301) 654-7850; FAX: (301) 654-4137. Internet: http://www.aagpgpa.org. PRICE: $2.50. Summary: This booklet provides information about diagnosing and treating people with dementia who have related behavioral disorders. It describes the nosology (classification) and prevalence, pathophysiology, and evaluation and treatment, including antipsychotics, anxiolytics, anticonvulsants, and antidepressants. Behavioral disturbances in people with dementia are common and a cause of impaired quality of life for both the patient and caregiver. Though the pathophysiology of these behavioral manifestations is not certain, various theories have been proposed. A recommended approach to treatment should involve conducting a thorough patient assessment, treating all relevant medical and psychiatric disorders, beginning treatment with nonpharmacologic techniques, using metaphor clusters to guide therapy, initially using non-antipsychotics, and following established guidelines. 6 figures, 6 tables, 52 references.
•
Diagnosis and Treatment Source: in Scully, C. Handbook of Oral Disease: Diagnosis and Management. New York, NY: Thieme New York. 2001. p.385-406. Contact: Available from Thieme New York. 333 Seventh Avenue, New York, NY 10001. (212) 760-0888, ext 110. PRICE: $35.00 plus shipping and handling. ISBN: 1841840874. Summary: This chapter on diagnosis and treatment is the final chapter in a handbook of oral disease that is intended to be used by all members of the dental team who need a ready office reference. The handbook covers the more common and important soft tissue orofacial disorders and gives clinically relevant aspects of the etiology, diagnosis, treatment, and prevention. In this chapter, the authors review certain management procedures that are commonplace. The purpose of making a diagnosis is to be able to offer the most effective treatment, safest treatment, and most accurate prognosis. Diagnosis most importantly involves a careful history. Dental staff should inquire about extraoral lesions; observe the patient's affect, behavior, movements, and gait; and inspect and examine the hands, fingers, nails, wrists, face, and neck and cervical lymph nodes. A careful inspection and examination of the oral and perioral structures is mandatory. The authors also discuss diagnostic tests, biopsy, biopsy technique, histology, lymph nodes, the use of frozen sections for rapid diagnosis, and oral smears for cytology. Management issues discussed include oral hygiene, diet, treatment of oral lesions, analgesia (painkillers), immunosuppressive agents, retinoids, antimicrobials, antifungals, antivirals, antidepressants, and when to refer to a specialist. Much of the information is provided in table or outline format for ease of reference. Full color photographs illustrate some conditions. 4 figures. 11 tables. 57 references.
Books
•
159
Geriatrics at Your Fingertips Source: New York, NY: American Geriatrics Society. 2000. 190 p. Contact: Available from Kendall Hunt Publishing Company. 4050 Westmark Drive, PO Box 1840, Dubuque, IA 52004-1840. (800) 338-8290, (319) 589- 1000. Internet: http://www.kendallhunt.com. PRICE: $10.95 plus $2.50 shipping and handling. ISBN: 444019480. LC number: 99-75691. Summary: This pocket-sized geriatrics reference book has chapters on dementia, delirium, and depression in older adults. The chapter on dementia includes information about the definition of dementia, estimated frequencies of different types of dementia, the diagnosis of Alzheimer's disease (AD), the different stages of AD, noncognitive symptoms, risk and protective factors for AD, evaluation, nonpharmacologic and pharmacologic treatment approaches, and caregiver issues. The chapter on delirium discusses diagnosis, potential causes, and management strategies. The chapter on depression focuses on evaluation and treatment with nonpharmacologic and pharmacologic approaches and electroconvulsant therapy; it includes tables listing antidepressants used for older adults and antidepressants to avoid in older adults. Includes index.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “antidepressants” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “antidepressants” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “antidepressants” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A handbook of psychoactive medicines : tranquillizers, antidepressants, sedatives, stimulants, narcotics, psychedelics by Terence DuQuesne; ISBN: 0704333937; http://www.amazon.com/exec/obidos/ASIN/0704333937/icongroupinterna
•
Antidepressant Therapy: At the Dawn of the Third Millennium by Mike Briley, Stuart A. Montgomery; ISBN: 185317517X; http://www.amazon.com/exec/obidos/ASIN/185317517X/icongroupinterna
•
Antidepressant Treatment-The Essentials by John H. Greist, Thomas H. Greist (1979); ISBN: 0683035916; http://www.amazon.com/exec/obidos/ASIN/0683035916/icongroupinterna
•
Antidepressants by Graham Burrows; ISBN: 0444804749; http://www.amazon.com/exec/obidos/ASIN/0444804749/icongroupinterna
•
Antidepressants (Drug Abuse Prevention Library) by Holly Cefrey (2000); ISBN: 0823932834; http://www.amazon.com/exec/obidos/ASIN/0823932834/icongroupinterna
•
Antidepressants (Drug Library) by Judy Monroe; ISBN: 0894908480; http://www.amazon.com/exec/obidos/ASIN/0894908480/icongroupinterna
160 Antidepressants
•
Antidepressants (Drugs: The Straight Facts) by E. Siobhan Mitchell, David J., Ph.d Triggle (Editor) (2003); ISBN: 0791076350; http://www.amazon.com/exec/obidos/ASIN/0791076350/icongroupinterna
•
Antidepressants (Milestones in Drug Therapy) by B. E. Leonard (Editor); ISBN: 3764359331; http://www.amazon.com/exec/obidos/ASIN/3764359331/icongroupinterna
•
Antidepressants : neurochemical, behavioral, and clinical perspectives; ISBN: 0890045348; http://www.amazon.com/exec/obidos/ASIN/0890045348/icongroupinterna
•
Antidepressants and Lithium: Their Uses and Side Effects by Edgar A. Monton; ISBN: 1857081919; http://www.amazon.com/exec/obidos/ASIN/1857081919/icongroupinterna
•
Antidepressants and Receptor Function - Symposium No. 123 by CIBA Foundation Symposium (Author); ISBN: 0471910899; http://www.amazon.com/exec/obidos/ASIN/0471910899/icongroupinterna
•
Antidepressants for Elderly People by Karabi Ghose (Editor) (1990); ISBN: 0412324601; http://www.amazon.com/exec/obidos/ASIN/0412324601/icongroupinterna
•
Antidepressants: New Pharmacological Strategies by Phil Skolnick (Editor); ISBN: 0896034690; http://www.amazon.com/exec/obidos/ASIN/0896034690/icongroupinterna
•
Antidepressants: Past, Present and Future (Handbook of Experimental Pharmacology, 157) by Renato D. Alarcon (Editor), Sheldon Preskorn (Editor) (2004); ISBN: 3540430547; http://www.amazon.com/exec/obidos/ASIN/3540430547/icongroupinterna
•
Beyond Prozac: Brain-Toxic Lifestyles, Natural Antidotes & New Generation Antidepressants by Michael J., M.D. Norden; ISBN: 0060391510; http://www.amazon.com/exec/obidos/ASIN/0060391510/icongroupinterna
•
Clinical Pharmacology in Psychiatry: Neuroleptic and Antidepressant Research by Earl Usdin (Editor); ISBN: 0333310888; http://www.amazon.com/exec/obidos/ASIN/0333310888/icongroupinterna
•
Depression and Antidepressants by Friedman (1988); ISBN: 0890045739; http://www.amazon.com/exec/obidos/ASIN/0890045739/icongroupinterna
•
Depression and Antidepressants: A Guide by James W. Jefferson, et al (1999); ISBN: 1890802190; http://www.amazon.com/exec/obidos/ASIN/1890802190/icongroupinterna
•
Differential Effects of Antidepressants by Brian E. Leonard, David Healy; ISBN: 1853176575; http://www.amazon.com/exec/obidos/ASIN/1853176575/icongroupinterna
•
Duloxetine - The Next Blockbuster Antidepressant? [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B0000AUH5S; http://www.amazon.com/exec/obidos/ASIN/B0000AUH5S/icongroupinterna
•
Handbook of Pharmacology of Antidepressants by L. Thakore (1998); ISBN: 185873309X; http://www.amazon.com/exec/obidos/ASIN/185873309X/icongroupinterna
Books
161
•
Listening to Prozac : A Psychiatrist Explores Antidepressant Drugs and the Remaking of the Self by Peter D. Kramer (Author); ISBN: 0788155245; http://www.amazon.com/exec/obidos/ASIN/0788155245/icongroupinterna
•
Listening to Prozac/a Psychiatrist Explores Antidepressant Drugs and the Remaking of the Self by Peter D. Kramer; ISBN: 0670841838; http://www.amazon.com/exec/obidos/ASIN/0670841838/icongroupinterna
•
Living With Tricyclic Antidepressants: Personal Accounts of Life on Tofranil (Imipramine, Pamelor) by Debra Elfenbein (Editor), Peter D. Kramer; ISBN: 0062512099; http://www.amazon.com/exec/obidos/ASIN/0062512099/icongroupinterna
•
Making The Antidepressant Decision, Revised Edition by Carol Turkington, Eliot F., MD Kaplan; ISBN: 0737304170; http://www.amazon.com/exec/obidos/ASIN/0737304170/icongroupinterna
•
Making the Prozac Decision: A Guide to Antidepressants by Carol Ann Turkington, et al; ISBN: 1565658035; http://www.amazon.com/exec/obidos/ASIN/1565658035/icongroupinterna
•
Natural Antidepressants by Syd Baumel; ISBN: 0879839007; http://www.amazon.com/exec/obidos/ASIN/0879839007/icongroupinterna
•
New Directions in Antidepressant Therapy (Royal Society of Medicine International Congress and Symposia Series, No 46) by S. Gershon, et al; ISBN: 0808914057; http://www.amazon.com/exec/obidos/ASIN/0808914057/icongroupinterna
•
New Therapeutic Indications of Antidepressants (International Academy for Biomedical and Drug Research (Series), Vol 12) by J. Mendlewicz (Editor), et al (1997); ISBN: 3805564368; http://www.amazon.com/exec/obidos/ASIN/3805564368/icongroupinterna
•
Prozac and Other Antidepressants (Junior Drug Awareness) by Stephen Bird, et al (2000); ISBN: 0791052044; http://www.amazon.com/exec/obidos/ASIN/0791052044/icongroupinterna
•
Prozac and the New Antidepressants: What You Need to Know About Prozac, Zoloft, Paxil, Luvox, Wellbutrin, Effexor, Serzone, Vestra, Celexa, St. John's Wort, and Others by William S. Appleton (2000); ISBN: 0452281644; http://www.amazon.com/exec/obidos/ASIN/0452281644/icongroupinterna
•
Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants with Safe, Effective Alternatives by Joseph Glenmullen (Author); ISBN: 0743200624; http://www.amazon.com/exec/obidos/ASIN/0743200624/icongroupinterna
•
Prozac: Panacea or Pandora? the Rest of the Story on the New Class of Ssri Antidepressants Prozac, Zoloft, Paxil, Lovan, Luvox & More. by Chase Shephard (Illustrator), et al (1994); ISBN: 0916095592; http://www.amazon.com/exec/obidos/ASIN/0916095592/icongroupinterna
•
Psychopharmacology of Antidepressants by J.H. Thakore (1999); ISBN: 1858732875; http://www.amazon.com/exec/obidos/ASIN/1858732875/icongroupinterna
•
Psychopharmacology of Antidepressants by Stephen M. Stahl, Stephen M Stahl; ISBN: 1853175137; http://www.amazon.com/exec/obidos/ASIN/1853175137/icongroupinterna
162 Antidepressants
•
Psychopharmacology of Anxiolytics and Antidepressants by Sandra E. File (Editor); ISBN: 008040698X; http://www.amazon.com/exec/obidos/ASIN/008040698X/icongroupinterna
•
Psychosocial Aspects of Nonresponse to Antidepressant Drugs by Uriel Halbreich (Editor); ISBN: 0880481293; http://www.amazon.com/exec/obidos/ASIN/0880481293/icongroupinterna
•
Psychotropic Agents Part I: Antipsychotics and Antidepressants by F. Hoffmeister, G. Stille; ISBN: 0387098585; http://www.amazon.com/exec/obidos/ASIN/0387098585/icongroupinterna
•
Reversible Mao a Inhibitors As Antidepressants: Basic Advances and Clinical Perspectives (Journal of Neural Transmission, Supplementum 28) by M. Da Prada (Editor), Graham D. Burrows; ISBN: 0387821333; http://www.amazon.com/exec/obidos/ASIN/0387821333/icongroupinterna
•
The Antidepressant Era by David Healy (1999); ISBN: 0674039580; http://www.amazon.com/exec/obidos/ASIN/0674039580/icongroupinterna
•
The Antidepressant Sourcebook: A User's Guide for Patients and Families by Andrew L., Md. Morrison; ISBN: 0385496656; http://www.amazon.com/exec/obidos/ASIN/0385496656/icongroupinterna
•
The Antidepressant Survival Guide: The Clinically Proven Program to Enhance the Benefits and Beat the Side Effects of Your Medication by Robert J. Hedaya (2001); ISBN: 060980541X; http://www.amazon.com/exec/obidos/ASIN/060980541X/icongroupinterna
•
The Antidepressant Survival Program: How to Beat the Side Effects and Enhance the Benefits of Your Medication by Robert J. Hedaya, Deborah Kotz (Contributor); ISBN: 0609604651; http://www.amazon.com/exec/obidos/ASIN/0609604651/icongroupinterna
•
The Cardiovascular Effects of Antidepressants by S J Warrington (Author), et al; ISBN: 0521388228; http://www.amazon.com/exec/obidos/ASIN/0521388228/icongroupinterna
•
The Hypericum Handbook: Nature's Antidepressant by Carol Turkington (1998); ISBN: 0871318571; http://www.amazon.com/exec/obidos/ASIN/0871318571/icongroupinterna
•
The Natural Prozac Program: How to Use St. John's Wort, the Antidepressant Herb by Jonathan Zuess; ISBN: 060980152X; http://www.amazon.com/exec/obidos/ASIN/060980152X/icongroupinterna
•
The New Antidepressants and Antianxieties by William S., MD Appleton (2004); ISBN: 0452285151; http://www.amazon.com/exec/obidos/ASIN/0452285151/icongroupinterna
•
The Omega-3 Connection: The Groundbreaking Omega-3 Antidepressant Diet and Brain Program [DOWNLOAD: MICROSOFT READER] by Andrew L. Stoll (2001); ISBN: B00005ORDR; http://www.amazon.com/exec/obidos/ASIN/B00005ORDR/icongroupinterna
•
The spectrum of antidepressant effect : proceedings of a symposium; ISBN: 9021915340; http://www.amazon.com/exec/obidos/ASIN/9021915340/icongroupinterna
Books
163
•
TREATING A DEPRESSED PATIENT WITH TRICYCLIC ANTIDEPRESSANTS Ruzyla-Smith (1994); ISBN: 0683156977; http://www.amazon.com/exec/obidos/ASIN/0683156977/icongroupinterna
•
Tricyclic antidepressants; ISBN: 0842241140; http://www.amazon.com/exec/obidos/ASIN/0842241140/icongroupinterna
•
Typical and Atypical Antidepressants: Clinical Practice (Advances in Biochemical Psychopharmacology: Vol 32) by Erminio Costa (Editor) (1982); ISBN: 0890048304; http://www.amazon.com/exec/obidos/ASIN/0890048304/icongroupinterna
•
Understanding Antidepressants by Mike Briley (2000); ISBN: 1853179558; http://www.amazon.com/exec/obidos/ASIN/1853179558/icongroupinterna
•
Zoloft, Paxil, Luvox and Prozac: All New Information to Help You Choose the Right Antidepressant by Donald L. Sullivan, Craig Williams (Introduction); ISBN: 0380795183; http://www.amazon.com/exec/obidos/ASIN/0380795183/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “antidepressants” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
A handbook of psychoactive medicines: tranquillizers, antidepressants, sedatives, stimulants, narcotics, psychedelics Author: DuQuesne, Terence,; Year: 1982; London; New York: Quartet Books, 1982; ISBN: 0704322706 http://www.amazon.com/exec/obidos/ASIN/0704322706/icongroupinterna
•
Acute cardiotoxicity of tricyclic antidepressants in rabbits and mice Author: Elonen, Erkki.; Year: 1975; Helsinki: [s.n.], 1975; ISBN: 951990638X
•
Antidepressants: thirty years on: proceedings of the Conference of the British Association for Psychopharmacology, held in University College, Galway, Ireland, in September 1988, and dedicated to Professor Max Hamilton, who died shortly before the conference Author: British Association for Psychopharmacology. Conference; Year: 1990; London: CNS (Clinical Neuroscience) Publishers, 1990; ISBN: 1869868749
•
Antidepressants. Edited by Stuart Fielding and Harbans Lal. Author: Fielding, Stuart.; Year: 1975; [Mount Kisco, N. Y.] Futura Pub. Co., 1975; ISBN: 0879930616 http://www.amazon.com/exec/obidos/ASIN/0879930616/icongroupinterna
•
Datis review of antidepressants in practice Author: Edwards, Sue.; Year: 1996; Daw Park, S. Aust.: Drug and Therapeutics Information Service, 1996; ISBN: 0958759812
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
164 Antidepressants
•
Effect of antidepressants and alcohol on psychomotor skills Author: Seppälä, Timo.; Year: 1978; Helsinki: [s.n.], 1978
•
New developments in the treatment of depressive illness: an update of the tetracyclics and other new generation antidepressants.; Year: 1984; Memphis, TN: Physicians Postgraduate Press, c1984
•
Suicide prevention and antidepressants Author: Leonard, B. E.; Year: 1989; Copenhagen: Munksgaard, [1989]; ISBN: 8716148304
•
The choice of antidepressants for depression in primary care: evidence-based clinical practice guideline Author: North of England Evidence-Based Guideline Development Project.; Year: 1998; [ Newcastle upon Tyne?]: Centre for Health Services Research University of Newcastle upon Tyne: Centre for Health Economics, University of York, c1998; ISBN: 1870399862
•
The use of antidepressants among injecting drug users Author: Darke, Shane.; Year: 1999; [Sydney]: National Drug and Alcohol Research Centre, University of New South Wales, Australia, c1999; ISBN: 0733404790
•
Toxicity and adverse reaction studies with neuroleptics and antidepressants. Skin-eye syndrome and electrocardiographic changes, edited by H. E. Lehmann and T. A. Ban. Author: Quebec Psychopharmacological Research Association.; Year: 1967; [Verdun, 1967?]
•
Update on the use of antidepressants in general practice: proceedings of the European CNS Advisory Board Seventh Plenary Meeting held in Prague, Czech Republic, on 24 January 1998. Author: European CNS Advisory Board. Plenary Meeting; Year: 1998; London; New York, NY: Royal Society of Medicine Press, c1998; ISBN: 1853153656
Chapters on Antidepressants In order to find chapters that specifically relate to antidepressants, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and antidepressants using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “antidepressants” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on antidepressants: •
Behavioral and Psychiatric Disorders Source: in Little, J.W., et al. Dental Management of the Medically Compromised Patient. 5th ed. St. Louis, MO: Mosby, Inc. 1997. p. 546-575. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $48.00 plus shipping and handling. ISBN: 0815156340. Summary: A working knowledge of the multitude of compromised health states is essential for dental professionals, as the majority of medically compromised patients need or want oral health care. This chapter on behavioral and psychiatric disorders is from a text that provides the dental practitioner with an up to date reference work describing the dental management of patients with selected medical problems. In this chapter, the authors discuss problems encountered in dental practice that stem from a
Books
165
patient's behavioral patterns rather than from physical conditions. The authors stress that both patients with emotional factors that contribute to oral or systemic problems and patients with more serious mental disorders can be managed in an understanding, safe, and empathetic manner. The authors discuss incidence and prevalence of anxiety disorders, mood disorders, and somatoform disorders; psychologic factors affecting physical conditions, including substance abuse, schizophrenia, and organic mental syndromes (dementia, Alzheimer's disease, delirium); etiology; pathophysiology and complications; signs and symptoms (clinical presentation and laboratory findings); drugs used to treat psychiatric disorders; and the dental management of this population, including patient attitude toward the dentist, the psychologic significance of the oral cavity, and behavior toward illness; and management of specific patients, including those with depression bipolar disorder, somatoform disorder, psychophysiologic disorder, a cocaine habit, schizophrenia, Alzheimer's disease, and suicidal patients. The chapter concludes with a section on drug interactions and side effects in patients with mental disorders, including tricyclic antidepressants, monoamine oxidase inhibitors, antianxiety drugs, and antipsychotic drugs. 3 figures. 25 tables. 40 references. •
Pain Management Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 593-597. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Although pain frequently is considered only a symptom of disease, it can be extremely debilitating, and is a major reason patients seek physicians' services. This chapter on pain management is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). To provide comprehensive pain management, it is important to understand the disease process, the biologic basis of pain, and the emotional state of the patient. The first goal in pain management is to establish an accurate diagnosis; then, an attempt is made to cure the disease, and thus eliminate sources of pain whenever possible; finally, strategies to minimize the suffering associated with pain are developed and implemented. When it is not possible to cure the disease, the management of pain becomes paramount. A thorough understanding of pain, its neural substrate, and the options available for its treatment currently are considered part of good medical practice. This chapter focuses on chronic abdominal, visceral pain that persists beyond either the course of an acute disease or a reasonable time for an injury to heal, is associated with a chronic pathologic process that causes continuous pain, or that recurs at intervals of months or years. The authors review medical therapies, including opioids, the risks of opioid therapy, nonsteroidal antiinflammatory drugs (NSAIDs), tricyclic antidepressants, anticonvulsants, intraspinal opioids, and neurolytic blocks. The authors emphasize that the risks of treating patients with pain are minimal, while the benefits can be life altering for the patients. 1 figure. 2 references.
•
Other Medicines for ADHD Source: in Barkley, R.A. Taking Charge of ADHD: The Complete, Authoritative Guide for Parents. New York, NY: Guilford Press. 2000. p. 288-293.
166 Antidepressants
Contact: Available from Guilford Publications. 72 Spring Street, New York, NY 10012. (800) 365-7006. Fax (212) 966-6708. E-mail:
[email protected]. Website: www.guilford.com. PRICE: $18.95 plus shipping and handling. ISBN: 1572305606. Summary: Children whose problems with attention, overactivity, and lack of inhibition reach a certain level have a developmental disability known as attention deficit hyperactivity disorder (ADHD). This chapter on medications (drug therapy) is from a book intended to help parents who are raising a child with ADHD and for others who wish to know more about the disorder and its management. The author's main goal is to empower parents to take charge of the care of these often demanding children in a way that ensures the health of the entire family, collectively and individually. In this chapter, the author focuses on drugs other than stimulants, the drugs most commonly used. Although they are not as effective as the stimulants, several drugs called antidepressants and a drug called clonidine, used to treat high blood pressure, can be of some benefit to those with ADHD. The author reviews the tricyclic antidepressants, including Norpramin or Pertofrane (desipramine), Tofranil (imipramine), and Elavil (amitriptyline), covering side effects, drug interactions, and how these drugs are used with children. The author then discusses Wellbutrin (buproprion hydrochloride), and clonidine (usually marketed under its generic name), including side effects and how these drugs are used with children. •
Detrusor Instability Source: in Ostergard, D.R. and Bent, A.E., eds. Urogynecology and Urodynamics: Theory and Practice. Baltimore, MD: Williams and Wilkins. 1996. p. 465-475. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. E-mail:
[email protected]. PRICE: $112.00. ISBN: 068306648X. Summary: Detrusor instability (DI, also called unstable bladder) describes the occurrence of uncontrolled bladder activity resulting in lower urinary tract symptoms. This chapter on DI is from a textbook on urogynecology and urodynamics that is designed to promote a more active role for the obstetrician, gynecologist, urologist, and other physicians in the evaluation of the female lower urinary tract. The author discusses the incidence of DI, its clinical presentation, differential diagnosis, etiology, disorders of the bladder ganglia, disorder of pacemaker cells, generalized smooth muscle disorder, increased sensory nerve activity, deficiency of prostacyclin production, local bladder irritation, outflow obstruction, anti-incontinence surgery, psychological treatments, diagnosis, management issues, bladder training (timed voiding), electrical stimulation, and medications (anticholinergics, tricyclic antidepressants, nonsteroidal anti-inflammatory agents, calcium channel blockers). The author concludes that surgery should be considered only after behavioral or medical therapy has failed because the surgery is associated with advanced morbidity. The two procedures most commonly performed are augmentation intestinocystoplasty and bladder denervation. The risks of the cystoplasty surgery include voiding difficulties, mucus or stone formation, and metabolic problems. Complications of bladder denervation can include perineal hypethesia, wound infection, and intraoperative bleeding. Long term followup revealed that after bladder denervation, 50 percent had persistent or recurrent incontinence and an additional 20 percent were dry only with the addition of anticholinergic agents. 3 figures. 3 tables. 56 references.
Books
•
167
Dyspepsia Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume One. Philadelphia, PA: Current Medicine. 1999. p. 226-235. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: Dyspepsia (heartburn or indigestion) is a poorly defined symptom complex of major importance because it affects a large proportion of the population. This chapter on dyspepsia is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. The author examines the pathophysiology, clinical presentation, and approach to management of patients with functional or nonulcer dyspepsia. The mechanisms that produce symptoms in these patients are not well understood, but can include acid hypersecretion, motor disorders, abnormalities in visceral perception, psychological factors, gastritis, and environmental agents (such as foods or alcohol). The typical presentation of patients with dyspepsia is epigastric (in the middle part of the abdomen) pain, usually occurring in relation to meals. Differential diagnosis should include peptic ulcer disease (PUD), biliary tract disease, pancreatic disease, gastroesophageal reflux, and other conditions such as cardiovascular disease. Treatment strategies for dyspepsia are directed at the various potential mechanisms of the syndrome: antisecretory agents to stem possible acid hypersecretion, prokinetics to counteract potential motility abnormalities, antidepressants to block afferent proprioceptive fibers, antibiotics to combat Helicobacter pylori gastritis, and other agents to treat irritable bowel like symptoms. The author offers an algorithm for the management of nonulcer dyspepsia. 4 figures. 3 tables. 32 references.
•
Functional Abdominal Pain Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 61-70. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: Functional abdominal pain is one of the most common reasons for consulting a physician, accounting for approximately 40 percent of visits to gastroenterologists. This chapter, from a gastroenterology text, examines the pathophysiology, diagnosis, and treatment of functional abdominal pain. Topics include the classification of subtypes of functional abdominal pain; the physiologic mechanisms for symptoms; the related psychologic factors; the differential diagnosis of functional abdominal pain; the role of education and reassurance in treating abdominal pain; dietary management; drug therapy, including the use of anticholinergic compounds, opiate analogs, antidepressants, and tranquilizers; and the role of psychotherapy, hypnotherapy, cognitive behavior therapy, progressive muscle relaxation training, and problems with ascertainment bias and placebo effects. The diagnostic assessment of these patients is guided by exclusion of alternative disease explanations for the symptoms; determining that the patient satisfies positive diagnostic criteria for a functional disorder, and testing for comorbid psychiatric disorders. The first line of treatment for functional abdominal pain is conservative treatment based on establishing a trusting relationship with the patient; providing education about the natural history of the disorder and factors such
168 Antidepressants
as diet and stress that are likely to influence it; and reassuring the patient that they do not have cancer or other life threatening conditions. Such conservative management is all that is required for 68 percent of patients with functional abdominal pain. In patients who fail to respond to conservative management, tricyclic antidepressants may provide the most cost effective second line of treatment. 3 tables. 67 references. (AA-M). •
Hiccups: Reasons and Remedies Source: in Lewis, J.H., ed. Pharmacologic Approach to Gastrointestinal Disorders. Baltimore, MD: Williams and Wilkins. 1994. p. 209-227. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4000. Fax (410) 528-4414. PRICE: $85 (as of 1995). ISBN: 0683049704. Summary: In this chapter, from a book on the pharmacologic approach to gastrointestinal disorders, the author explains the pathophysiology of hiccups. The author describes nonpharmacologic treatments first because most individuals attempt a physical or mechanical maneuver to stop hiccups before drug therapy. Specific topics include hiccup frequency; conditions associated with hiccups; hiccups due to anesthesia and surgery; hiccup epidemics; gastrointestinal causes of hiccups; historical cures; the physical and mechanical means of treating hiccups; and drug therapy for hiccups, including the use of major tranquilizers, anticonvulsants, central nervous system stimulants, sedatives, hypnotics, muscle relaxants or antispasticity agents, narcotic analgesics, tricyclic antidepressants, calcium channel blocking agents, dopamine antagonists, dopamine agonists, parasympathomimetics, serotonin antagonists, and lidocaine; and guidelines for treating transient and persistent hiccups. 5 tables. 126 references.
•
Oral Medications Source: in Moldwin, R.M. Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies. Oakland, CA: New Harbinger Publications, Inc. 2000. p. 81-112. Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Fax (301) 610-5308. E-mail:
[email protected]. Website: www.ichelp.org. PRICE: $12.00 plus shipping and handling. ISBN: 1572242108. Summary: More than 700,000 Americans have interstitial cystitis (IC), a condition that includes symptoms of recurring bladder pain and discomfort on urination. This chapter on oral medications used to treat IC is from a self care book designed to empower readers by simplifying the diagnostic and treatment process for IC. The primary object of the book is to build a framework for delivering proper care to the IC patient. Oral medications, used alone or in combination with other medications, will improve symptoms in most patients with IC. Patients may still have some symptoms while on oral medications, but they may be improved to the point where they wish to wait before undergoing more invasive therapy. Most of the medications used cause few significant side effects. The author notes that most of the medications discussed in this chapter have been used for many years but for other purposes. Medications and dosages may need to be changed due to side effects or poor responses. The author first discusses medications thought to coat the bladder's surface, including pentosan polysulfate sodium (Elmiron), chondroitin sulfate, and glucosamine. The author then discusses the use of antidepressants (primarily to reduce pain), including amitriptyline (Elavil); selective
Books
169
serotonin reuptake inhibitors (SSRIs); antihistamines, including hydroxyzine (Atarax, Vistaril); cromolyn sodium (Gastrocrom); cimetidine (Tagamet); antiseizure medications, including gabapentin (Neurontin), and carbamazepine (Tegretol); nonsteroidal antiinflammatory drugs (NSAIDs); immunosuppressants, including steroids; muscle relaxants, notably diazepam (Valium); narcotic therapy; urinary anesthetics, including phenazopyridine hydrochloride (Pyridium), atropine sulfate, benzoic acid, hyoscyamine, methenamine, methylene blue, and phenyl salicylate (Urised); anticholinergic therapy; L arginine; calcium channel blockers, including nifedipine (Procardia); and alpha blockers. The author reviews the use of each of these drugs, along with the hypothesis about why they may be of use in IC. •
Chronic Abdominal Pain: The Functional Gastrointestinal Disorders Source: in Edmundowicz, S.A., ed. 20 Common Problems in Gastroenterology. New York, NY: McGraw-Hill, Inc. 2002. p. 81-91. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $45.00;plus shipping and handling. ISBN: 0070220557. Summary: The term, functional gastrointestinal disorders, covers a variable combination of chronic, recurrent upper gastrointestinal disorders (dyspepsia) or lower gastrointestinal irritable bowel syndrome (IBS) symptoms, where an organic pathologic process or structural abnormality is absent. This chapter on chronic abdominal pain (the functional gastrointestinal disorders) is from a book that focuses on the most common gastroenterological problems encountered in a primary practice setting. The chapter is organized to support rapid access to the information necessary to evaluate and treat most patients with this problems. Topics include the prevalence of these disorders; principal diagnoses; the typical presentation of functional dyspepsia and IBS; key elements to the patient history; the physical examination; diagnostic tests; treatment options including antacids, acid suppression, prokinetics, and psychotherapy for functional dyspepsia, and diet, antispasmodics, anticholinergics, prokinetics, antidepressants, and psychotherapy for IBS; patient education issues; clinical controversies; and emerging concepts. The chapter includes an outline for quick reference, the text itself, a diagnostic and treatment algorithm, and selected references. 2 figures. 2 tables. 32 references.
•
Antidiarrheals, Antibiotics, Psychotropics, and Potential New Drug Therapies Source: in Peppercorn, M.A., ed. Therapy of Inflammatory Bowel Disease: New Medical and Surgical Approaches. New York, NY: Marcel Dekker, Inc. 1990. p. 135-144. Contact: Available from Marcel Dekker, Inc. P.O. Box 5005, Monticello, NY 12701-5185. (800) 228-1160 or (212) 696-9000. Fax (914) 796-1772. E-mail:
[email protected]. PRICE: $190.00. ISBN: 0824781694. Summary: There are a number of drugs that can be of great use for the individual patient with inflammatory bowel disease (IBD), but whose action is not thought of as directed against IBD itself. There is also an increasing list of agents which appear to have some promise as first-line agents in IBD treatment. This chapter, from a book about the medical and surgical approaches in the management of IBD, discusses antidiarrheals, antibiotics, psychotropics, and potential new drug therapies, and their uses in IBD therapy. The author discusses antidiarrheals, including opiates, cholestyramine, and bulk agents; antibiotics, including sulfasalazine and metronidazole; and psychotropics, including minor tranquilizers and antidepressants. Potential new
170 Antidepressants
drug therapies, using agents including sodium cromoglycate, sucralfate, chloroquine, methotrexate, antituberculous agents, lipoxygenase inhibitors, and immune adjuvants, are discussed. 43 references. •
Medications Used To Treat Complications of Diabetes Source: in Carlisle, B.A.; Kroon, L.A.; Koda-Kimble, M.A. 101 Medication Tips for People with Diabetes. Alexandria, VA: American Diabetes Association. 1999. p. 66-75. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $14.95 plus shipping and handling. ISBN: 1580400329. Order number 483301. Summary: This chapter answers questions about the meditations used to treat diabetes complications, including nonprescription analgesics, tricyclic antidepressants, capsaicin cream, angiotensin converting enzyme (ACE) inhibitors, laxatives, and calcium channel blockers. Nonprescription analgesics, antidepressants, and narcotic analgesics can be used to treat the pain associated with diabetic neuropathy. Capsaicin cream, a chemical found in hot chili peppers, can be applied to the feet to relieve pain. ACE inhibitors can be used to treat microalbuminuria, an early sign of kidney damage. The symptoms of gastroparesis, a condition that affects the nerves of the stomach, can be treated with metoclopramide, cisapride, and erythromycin. These medications increase the stomach's ability to contract and aid in digestion. Constipation can be treated by increasing the amount of fluid and fiber in a person's diet. Laxatives may also be useful in treating constipation. Men who have diabetes and experience impotence can use the medications alprostadil and sildenafil to maintain an erection. People who have diabetes and high blood pressure can be treated with ACE inhibitors, diuretics, and calcium channel blockers. Angiotensin receptor II antagonists and calcium channel blockers can be used to treat kidney disease. People who have diabetes should take any medications their doctor prescribes for other conditions, such as high blood pressure, heart disease, high cholesterol or triglycerides, obesity, and insulin resistance.
•
Drugs Used for Vertigo and Vomiting Source: in Bennett, D.R., ed. Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, Division of Toxicology. 1994. p. 439-464. Contact: Available from American Medical Association. Division of Drugs and Toxicology, 515 North State Street, Chicago, IL 64610. (312) 464-500. ISBN: 0899706029. PRICE: $78.00 for AMA members, $98.00 for nonmembers. Summary: This chapter discusses drugs that are effective in combating vertigo or nausea and vomiting. The vertigo section includes a description of vertigo; its causes; subjective vertigo; drug-induced vertigo; and Meniere's disease. The section also includes a discussion of drug selection for antivertigo drugs. Drugs discussed include scopolamine; antihistaminic drugs; antianxiety agents and antidepressants; diazepam (Valium); droperidol (Innovar); and fentanyl citrate (Sublimaze). The chapter concludes with the chemical formation, and a discussion of uses, adverse reactions and precautions, and dosage and preparations for each of the pharmaceuticals discussed. 1 table. 101 references.
Books
•
171
Irritable Bowel Syndrome and Diarrhea Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 502-510. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: This chapter from a gastroenterology text covers irritable bowel syndrome (IBS) and diarrhea. The IBS is a heterogeneous group of functional gastrointestinal tract disorders involving the small intestine and colon; central to the definition of IBS is abdominal pain. The authors first provide some background regarding aspects of the history, physical examination, and initial laboratory evaluation that supports the diagnosis of this common presentation. The authors caution against performing excessive diagnostic tests, which can undermine the patient's confidence in both the physician and the diagnosis, as well as play into the tendency of patients with IBS to seek opinions from multiple physicians. The authors also discuss the psychosocial support that is an important component in the management of a chronic disorder such as IBS. They recommend establishing early in the treatment plan a realistic goal of reducing and not eradicating symptoms, emphasizing that the physician and patient share responsibility for management decisions. Treatment options discussed include diet and bulking agents, opiates, anticholinergics, antispasmodics, peppermint oil, calcium channel blockers, allergy medicine, anxiolytics and antidepressants, and peptides and biogenic amines. 1 figure. 2 tables. 49 references.
•
Effective Therapies Source: in Manu, P. Pharmacotherapy of Common Functional Syndromes: EvidenceBased Guidelines for Primary Care Practice. Binghamton, NY: Haworth Medical Press. 2000. p. 125-130. Contact: Available from Haworth Medical Press, an imprint of Haworth Press, Inc. 10 Alice Street, Binghamton, New York 13904-1580. (800) HAWORTH or (800) 429-6784. Outside United States and Canada (607) 722-5857. Fax (800) 895-0582. E-mail:
[email protected]. Website: www.haworthpressinc.com. PRICE: $69.95 plus shipping and handling. ISBN: 0789005883. Summary: This chapter is from a book that evaluates drug therapies for each of the four major functional disorders: chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome (IBS), and premenstrual syndrome. In this chapter, the second of six short chapters that focus on IBS, the author introduces and reviews the effective therapies for the condition. The author focuses on the tricyclic antidepressants, notably amitriptyline, trimipramine, and desipramine. The author discusses some of the basic research on each drug's use in patients with IBS. Amitriptyline improved the symptoms of 79 percent of the patients studied. The improvement reached a highly significant level when baseline symptoms were compared to the status immediately following the administration of the tricyclic drug. Amitriptyline induced improvement was more frequently observed among patients whose IBS was of moderate severity and among those whose baseline evaluation indicated high depression and anxiety scores. Compared with placebo, treatment with trimipramine significantly reduced the severity of vomiting, sleeplessness, and depression, as well as the presence of mucus in stool. However, for the other six target symptoms, including the main complaint of abdominal pain, the frequency and severity was reduced to a similar degree in both the placebo and trimipramine groups. Closely related to trimipramine, desipramine resulted in
172 Antidepressants
improvement in 54 percent of the patients in one study reported. The diarrhea predominant cases were more likely to respond to desipramine (68 percent) than the constipation predominant subgroup (22 percent). •
Medical Treatments Source: in Saunders, J. Tinnitus: What is That Noise in My Head? Auckland, New Zealand: Sandalwood Enterprises. 1994. p. 31-42. Contact: Available from American Tinnitus Association (ATA). P.O. Box 5, Portland, OR 97207-0005. (800) 634-8978 or (503) 248-9985. Fax (503) 248-0024. E-mail:
[email protected]. Website: www.ata.org. PRICE: $14.50 for members; $18.00 for nonmembers. ISBN: 0473015625. Summary: This chapter is from a book that familiarizes readers with the common causes and symptoms of tinnitus and explains how people with tinnitus can take steps toward relieving the condition. Written in non-technical language, the chapter outlines medical treatments for tinnitus. Topics covered include drug therapy with Tegretol (carbamazepine), Serc (betahistine hydrochloride), sleeping tablets, antidepressants, aspirin products (salicylates), quinine, and caffeine; the adverse effects of smoking; drug research; surgery; otosclerosis; Meniere's disease; acoustic neuromas; pulsatile tinnitus; temporomandibular jaw dysfunction (TMJ); and the role of jaw exercises.
•
Medical, Dietetic, and Surgical Treatments Source: in Blakley, B.W.; Siegel, M.E. Feeling Dizzy: Understanding and Treating Dizziness, Vertigo, and Other Balancing Disorders. New York, NY: Macmillan Publishing. 1995. p. 153-176. Contact: Available from Macmillan Publishing. 201 West 103rd Street, Indianapolis, IN 46290. (800) 428-5331; Fax (800) 882-8583. PRICE: $21.95 plus shipping and handling. ISBN: 0028600096. Summary: This chapter is from a layperson's guide to vertigo, imbalance, fainting, and other balance disorders. This chapter describes medical, dietetic, and surgical treatments for vestibular disorders. Topics covered include drug therapy such as vestibular suppressants, scopolamine, stimulants, antidepressants and antianxiety drugs, diuretics, and aminoglycosides; diet therapy, including lower dietary salt, the role of caffeine, and suggestions for dietary management; considering surgery, including choosing a surgeon, deciding on the hospital; and surgical techniques of endolymphatic sac surgery, the tack operation, cochleosacculotomy, perilymph fistula surgery, labyrinthectomy, vestibular nerve section, vascular loop surgery, surgery for BPPV, myringotomy and tympanostomy tubes, and stapedectomy. 1 figure. 1 table.
•
Irritable Bowel Syndrome Source: in King, J.E., ed. Mayo Clinic on Digestive Health. Rochester, MN: Mayo Clinic. 2000. p. 89-98. Contact: Available from Mayo Clinic Health Information. 5505 36th Street, SE, Grand Rapids, MI 49512. (800) 291-1128. Website: www.mayoclinic.com. PRICE: $14.95 plus shipping and handling. ISBN: 1893005046. Summary: This chapter on irritable bowel syndrome (IBS) is from a comprehensive guidebook from the Mayo Clinic that focuses on a variety of digestive symptoms, including heartburn, abdominal pain, constipation, and diarrhea, and the common
Books
173
conditions that are often responsible for these symptoms. Written in nontechnical language, the book includes practical information on how the digestive system works, factors that can interfere with its normal functioning, and how to prevent digestive problems. This chapter first reviews the key signs and symptoms of IBS, including abdominal pain or discomfort, bloating or gas, diarrhea, constipation, and mucus in stool (feces). The authors explain that IBS is a functional disorder, which means that the intestines look normal, but they function abnormally. As there is no cure for IBS, the focus of treatment is on managing the patient's symptoms so that they can participate in normal activities and fully enjoy life. Treatment is usually twofold: identify factors that trigger the symptoms, and develop strategies to minimize symptoms. The authors then review some of these strategies, including eat low fat foods, experiment with fiber, drink plenty of liquids, avoid problem foods, eat at regular times, include exercise daily, and learn to manage stress. Another section of the chapter reviews the medical treatment that can be used for more severe symptoms of IBS, including prescription medications, such as alosetron (Lotronex), smooth muscle relaxants, and antidepressants, and counseling. Sidebars review drugs currently in development, a stress reduction relaxation exercise, and a discussion of the differences between lactose or sorbitol intolerance and IBS. 1 figure. •
Medical Therapy for Detrusor Incontinence Source: in Kursh, E.D. and McGuire, E.J. Female Urology. Philadelphia, PA: LippincottRaven Publishers. 1994. p. 103-118. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. PRICE: $108.00 plus shipping. ISBN: 039751154X. Summary: This chapter on medical therapy for detrusor incontinence is from a textbook of female urology, designed to enhance the education of urologists, gynecologists, or any other physicians caring for women. The author covers decreasing bladder contractility, with anticholinergic agents, musculotropic relaxants, calcium antagonists, alpha-adrenergic blocking agents, potassium channel openers, prostaglandin inhibitors, beta-adrenergic agonists, tricyclic antidepressants, dimethyl sulfoxide (DMSO), and polysynaptic inhibitors; increasing bladder capacity by decreasing sensory (afferent) input; and circumventing the problem with the use of antidiuretic hormonelike agents. 1 table. 92 references.
•
Treatment Source: in Palmer, M.H. Urinary Continence: Assessment and Promotion. Gaithersburg, MD: Aspen Publishers, Inc. 1996. p. 79-110. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, Frederick, MD 21704. (800) 234-1660 or (800) 638-8437. PRICE: $35.00. ISBN: 0834207478. Summary: This chapter on treatment options is from a text that provides nurses and other health care providers with a practical guide to urinary continence promotion in older adults. The author discusses the behavioral, pharmacological, and surgical treatment options available for the most common causes of urinary incontinence (UI) in older adults. The author also briefly discusses treatment for UI in long-term care, home care, and acute care settings. The author emphasizes that treatment for UI must be established only after a thorough assessment of the causes and factors related to the incontinence. A basic understanding of the pathophysiology of incontinence is needed by all individuals involved in the treatment and care plan. The affected older adult
174 Antidepressants
should be included in the decision-making process for treatment. Treatment options discussed include pelvic floor training, behavioral modification, bladder training, scheduled toileting, habit training, prompted voiding, electrical stimulation, surgery for men with overflow and stress UI, surgery for women with stress UI, anticholinergic medications, smooth muscle relaxants, tricyclic antidepressants, alpha-adrenergic agonists, estrogens, and voiding maneuvers. The chapter concludes with a discussion of the treatment of functional incontinence and a section on the treatment of transient incontinence due to urinary tract infections, fecal impaction, delirium, and medications. The author concludes that the cornerstone of the best approach to treatment is the realistic optimism of the health care team and the committed determination to alleviate the physical and emotional distress of UI. 1 figure. 4 tables. 44 references. (AA-M). •
Chapter 67: Movement Disorders Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 13 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides information on the symptoms, diagnosis, and treatment of various movement disorders, including tremors, cramps, myoclonus, hiccups, Tourette's syndrome, chorea, athetosis, Huntington's disease, dystonia, Parkinson's disease, progressive supranuclear palsy, Shy-Drager syndrome, and coordination disorders. Damage to or an abnormality of an area of the nervous system that regulates movement may cause a person to experience a movement disorder. A tremor is an involuntary, rhythmic, shaking movement that occurs when muscles repeatedly contract and relax. Types of tremors include action, resting, intention, essential, senile, and familial tremors. Although treatment is usually not needed for movement disorders, drugs may be helpful for some people. A cramp is a sudden, brief, usually painful contraction of a shortened muscle or group of muscles. Cramps are common in healthy people and do not need to be treated. Myoclonus causes a synchronous quick jerk of affected muscles. Antiseizure drugs may be used to treat severe cases of myoclonic jerks. Hiccups are repeated spasms of the diaphragm followed by quick, noisy closings of the glottis. They are caused when a stimulus triggers the nerves that contract the diaphragm. Most cures for hiccups require holding the breath to increase the amount of carbon dioxide in the blood. Stimulating the vagus nerve may also help. Tourette's syndrome is a hereditary disorder characterized by motor and vocal tics. Antipsychotic drugs may help suppress them. Chorea and athetosis are symptoms that can result from several different diseases, including Huntington's disease and Sydenham's disease. Drugs that block the action of dopamine may help control abnormal movements. Huntington's disease is an inherited disease characterized by abnormal movements and gradual loss of brain cells. There is no cure for Huntington's disease, but drugs may help relieve symptoms and control behavior. In people who have dystonia, muscles may freeze in the middle of an action. Dystonia seems to be caused by overactivity in several areas of the brain. Types of dystonia are idiopathic torsion dystonia, blepharospasm, torticollis, and spasmodic dysphonia. Treatment is limited. Drugs with anticholinergic properties may be helpful. Parkinson's disease is a progressive, degenerative disorder of the nervous system. Although the cause of nerve cell degeneration and dopamine loss is usually not known, Parkinson's disease is sometimes a very late complication of viral encephalitis or a complication of using certain drugs. Muscle stiffness develops in Parkinson's disease, and initiating a
Books
175
movement is difficult. Various drugs are used to treat this disease, including levodopa, bromocriptine, pergolide, selegiline, anticholinergics, antihistamines, antidepressants, propranolol, and amantadine. Progressive supranuclear palsy causes muscle rigidity, inability to roll the eyes upward, and weakness of the throat muscles. The cause is unknown, and there is no completely effective treatment. Shy-Drager syndrome causes malfunction and destruction of the autonomic nervous system. Treatment is the same as for Parkinson's disease but includes the drug fludrocortisone. Coordination disorders occur when the cerebellum is damaged. •
Chapter 55: Disorders of the Muscles, Bursas, and Tendons Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 6 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have disorders of muscles, bursas, and tendons with information on their symptoms, diagnosis, and treatment. Spasmodic torticollis is a painful intermittent or continuous spasm of the neck muscles that forces the head to rotate and tilt forward, backward, or sideways. Torticollis varies from mild to severe, and it may persist for life. Diagnosis is based on the medical history, a physical examination, and imaging tests. When a cause is identified, the torticollis can usually be treated successfully. However, treatment is less likely to be effective when the cause is a nervous system disorder or is unknown. Physical therapy or massage can sometimes relieve the spasm temporarily. Drugs such as anticholinergics and benzodiazepines are commonly used. Muscle relaxants and antidepressants may also be prescribed. Fibromyalgia syndromes are a group of disorders characterized by achy pain and stiffness in soft tissues throughout the body or only in certain locations. Widespread fibromyalgia is more common in women, whereas localized fibromyalgia is more common in men. The cause is unknown. The most commonly affected areas include the fibrous tissues or muscles of the neck, shoulders, chest, rib cage, lower back, and thighs. Diagnosis is based on the pattern and location of the pain. Nondrug treatments are usually more effective than drugs. Bursitis, which may be either acute or chronic, is the painful inflammation of a bursa caused by chronic overuse, injury, gout, pseudogout, rheumatoid arthritis, or infections. General symptoms include pain and limited movement. Specific symptoms depend on the location of the inflamed bursa. Bursitis is suspected if the area around a bursa is sore when touched and specific joint movements are painful. Antibiotics are used to treat infected bursas, whereas conservative measures and nonsteroidal antiinflammatory drugs are usually used to treat noninfectious acute bursitis. Chronic bursitis is treated similarly. Tendinitis is the inflammation of a tendon, and tenosynovitis is tendinitis accompanied by an inflammation of the sheath around the tendon. Symptoms of both disorders include pain and swelling. Treatment options that may alleviate the symptoms of tendinitis include conservative measures, nonsteroidal antiinflammatory drugs, and injection of corticosteroids and local anesthetics. 1 figure.
•
Enuresis Source: in Kher, K.K.; Makker, S.P., eds. Clinical Pediatric Nephrology. New York, NY: McGraw-Hill. 1992. p. 399-419.
176 Antidepressants
Contact: Available from McGraw-Hill, Inc. P.O. Box 545, Blacklick, OH 43004. (800) 2624729. PRICE: $85.00 plus $3.00 shipping and handling. ISBN: 0070345430. Summary: This chapter, from a book on clinical pediatric nephrology, discusses enuresis, or involuntary voiding of urine beyond the age of anticipated control. Topics include attaining bladder control; the epidemiology of enuresis; its etiology, including neurophysiologic maturational lag, developmental delay, antidiuretic hormone, sleep disorders, psychological factors, and urinary tract infection; evaluation of enuresis; treatment, including behavioral modification, conditioning therapy, motivational therapy, and bladder retention training; pharmacologic therapy, including the use of tricyclic antidepressants, antidiuretic hormone desmopressin (DDAVP), and anticholinergic drugs; and miscellaneous therapies. 4 figures. 119 references. •
Pharmacologic Therapy for Incontinence Source: in O'Donnell, P.D., ed. Geriatric Urology. Waltham, MA: Little, Brown and Company. 1994. p. 285-299. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail:
[email protected]. Website: http://www.lrpub.com. PRICE: $135.00. ISBN: 0316630039. Summary: This chapter, from a medical text on geriatric urology, considers pharmacologic therapy for incontinence. The authors discuss topics including the physiology of bladder function; aging bladder function; and uropharmacology of the lower urinary tract, including clinical uropharmacology and facilitating urine storage. Pharmacologic agents covered include anticholinergic agents; musculotropic relaxants; calcium antagonists; potassium channel openers; beta-adrenergic agonists; tricyclic antidepressants; dimethyl sulfoxide (DMSO); alpha-adrenergic agonists; betaadrenergic antagonists; estrogens; and DDAVP. 1 table. 103 references.
•
Management of the Irritable Bowel Syndrome Source: in Danzi, J.T.; Scopelliti, J.A., eds. Office Management of Digestive Diseases. Malvern, PA: Lea and Febiger. 1992. p. 102-111. Contact: Available from Lea and Febiger. Box 3024, Malvern, PA 19355-9725. (215) 2512230. PRICE: $39.50. ISBN: 0812114361. Summary: This chapter, from a medical textbook about the office management of common gastrointestinal diseases, discusses the management of the irritable bowel syndrome (IBS). Topics include pathogenesis, psychosocial factors, diagnosis, treatment issues, patient education, and specific therapy, including fiber supplements, anticholinergics, tranquilizers, opioids, antidepressants, and psychotherapy. The author stresses that successful treatment requires time, energy, and empathy; the interaction of the physician and the patient constitutes the treatment. 20 references.
•
Treatment of Non-Cognitive Features of Dementia Source: in Levy, R.; Howard, R.; Burns, A.; eds. Treatment and Care in Old Age Psychiatry. Petersfield, Hampshire, UK: Wrightson Biomedical Publishing Ltd. 1993. p. 47-57. Contact: Available from Taylor and Francis. 1900 Frost Road, Suite 101, Bristol, PA 19007-1598. (800) 821-8312 or (215) 785-5515 (FAX). PRICE: $85.00.
Books
177
Summary: This chapter, in a text concerning recent advances in the psychiatry of the aged, describes the psychiatric symptoms and behavioral disturbances that occur in patients with dementia, outlines their importance, and discusses their treatment. Noncognitive features, including delusions, hallucinations, mood changes, sleep disturbances, appetite changes, sexual changes, psychomotor changes, and personality changes, may have diagnostic value and may help to indicate subgroups of Alzheimer's disease. The chapter focuses on pharmacological treatment of these symptoms, with discussion of neuroleptic agents in general and specific discussion of non-neuroleptics. The latter include antidepressants, anticonvulsants, beta blockers, benzodiazepines, and psychostimulants. General recommendations for drug treatment are given, along with discussions of the drug and behavioral treatment of specific behaviors, including depression, delusions, anxiety, insomnia, aggression, shouting, wandering, and agitation. 27 references. •
Questions and Answers Source: in Tanner, D.C. Family Guide to Surviving Stroke and Communication Disorders. Needham Heights, MA: Allyn and Bacon. 1999. p. 227-240. Contact: Available from Allyn and Bacon. 160 Gould Street, Needham Heights, MA 02194. (800) 278-3525. Website: www.abacon.com. PRICE: $20.95. ISBN: 0205285384. Summary: This final chapter is from a book that offers families practical information on stroke related communication disorders. Through nontechnical terms, a short story, case studies, questions and answers, and examples, the book engages families, stroke and rehabilitation specialists, and counselors on a journey toward understanding and healing. In this chapter, the author answers a variety of questions that may not have been covered adequately in the book. Topics include patient advocacy, hygiene, activities of daily living, dealing with embarrassing situations, social activities, interpersonal communication (and lack thereof), managing frustration, the patient therapist relationship, drooling, handling anger (the family members' and the patient's), Broca's aphasia, nonsense or jargon speech, nonverbal communication, verbal apraxia, hoarseness, emotional lability, Alzheimer's disease, auditory agnosia, comas and awakening from long lasting comas, memory, the use of antidepressants, dentures, hallucination, dry mouth, tactile agnosia, tracheotomy, hearing aids, determining if a patient can benefit from speech language therapy, and music.
179
CHAPTER 8. MULTIMEDIA ON ANTIDEPRESSANTS Overview In this chapter, we show you how to keep current on multimedia sources of information on antidepressants. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on antidepressants is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “antidepressants” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “antidepressants” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on antidepressants: •
Rational Approach to the Diagnosis, Treatment and Management of Interstitial Cystitis Source: Rockville, MD: Interstitial Cystitis Association. 1994. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail:
[email protected]. Website: www.ichelp.org. PRICE: $14.50 (as of 1995). Summary: This professional education videotape provides clinicians with an overview of the diagnosis, treatment, and management of interstitial cystitis (IC). Narrated by Dr. Phillip Hanno, the program defines IC; describes the symptoms and the chronic nature of the disease; discusses the exclusionary diseases to consider in the diagnosis of IC; demonstrates the urodynamic workup of a suspected IC patient, including the role of cystoscopy, bladder distension, and biopsy; details the treatment options for IC, including hydrodistension, DMSO therapy, oxychlorosene sodium (Chlorpactin) therapy, the use of tricyclic antidepressants, the use of sodium pentosanpolysulfate
180 Antidepressants
(Elmiron-includes availability of this not-yet-approved drug) transcutaneous electrical nerve stimulation (TENS), narcotics, fulgeration, and surgery; and outlines self-care strategies including acid restriction and urine alkalization, exercise, stress reduction, acupressure, biofeedback, products and supplies, bladder holding protocol, and patient education and support. The program concludes with a brief discussion of the role of the Interstitial Cystitis Association (ICA) in research and patient education and support.
Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “antidepressants” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on antidepressants: •
Behavior Management With Psychotropic Medications Source: Redmond, WA: Tree Farm Cassettes. 1993. (audiocassette). Contact: Available from Tree Farm Cassettes. 23703 N.E. 4th Street, Redmond, WA 98053. (800) 468-0464 or (206) 868-2495 (FAX). PRICE: $9.00. Order Number: AP34060. Complete conference on cassettes available for $225.00. Summary: This audiocassette recording session at the 11th Annual Convention of the National Association of Activity Professionals, which took place in Milwaukee, Wisconsin, on April 14-17, 1993. The speaker discusses the principles of using psychotropic medications to treat behavioral disorders secondary to dementia. He emphasizes that Alzheimer's disease is incurable but that its symptoms are treatable, and that treating behavioral symptoms can improve the quality of life for patients and caregivers. Activity professionals can be part of a team that helps make decisions about the appropriate medications for individual patients, and they need to understand the effects that medications have on a patient's behavior. The author discusses the misuse of psychotropic medications, including excessive dosing, inadequate monitoring, inadequate indications, and excess duration, and the need to balance benefits and adverse effects. Federal guidelines for prescribing psychotropic drugs are examined. Some principles for prescribing psychotropics are outlined, including the need to document and quantify target behaviors, to define therapeutic objectives, to exhaust nonpharmacologic therapies before prescribing, to screen for underlying illness and drug effects, to consider pharmacokinetic and pharmacodynamic processes and how they are influenced by aging, to simplify the drug regimen, and to make changes in treatment strategies carefully and appropriately. The effects, acceptable and unacceptable uses, and regulatory guidelines for antipsychotics, antidepressants, and benzodiazepines are covered in detail, and general side effects are listed.
Bibliography: Multimedia on Antidepressants The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the
Multimedia 181
multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in antidepressants (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on antidepressants: •
Antidepressant pharmacology [videorecording]: an update Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1998; Format: Videorecording; Marshfield, WI: The Network, c1998
•
Antidepressants and lithium [videorecording] Source: University of Washington, School of Nursing, School of Pharmacy; Year: 1977; Format: Videorecording; [Seattle]: The University: [for loan or sale by University of Washington Press, 1977]
•
Cardiovascular effects of antidepressants [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital [and] Marshfield Medical Research Foundation; Year: 1990; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1990]
•
Other uses for antidepressants [videorecording] Source: with James W. Jefferson; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986
•
Sexual dysfunction and antidepressants [videorecording] Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1997; Format: Videorecording; Marshfield, WI: The Clinic, [1997]
•
The Cardiovascular effects of antidepressants [videorecording] Source: produced by the Department of Psychiatry and Behavioral Sciences and the Health Communications Network; Year: 1991; Format: Videorecording; Charleston, S.C.: Medical University of South Carolina, c1991
•
Treating a depressed patient with tricyclic antidepressants [electronic resource] Source: MEPC Software; Year: 1987; Format: Electronic resource; New York, N.Y.: Elsevier Science Pub. Co., c1987
•
Tricyclicness [sic] antidepressants benzodiazepines [videorecording] Source: [presented by] Marshfield Clinic and St. Joseph's Hospital; Year: 1982; Format: Sic; Marshfield, WI: Marshfield Regional Video Network, 1982
183
CHAPTER 9. PERIODICALS ANTIDEPRESSANTS
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover antidepressants.
News Services and Press Releases One of the simplest ways of tracking press releases on antidepressants is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “antidepressants” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to antidepressants. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “antidepressants” (or synonyms). The following was recently listed in this archive for antidepressants: •
Recordati launches antidepressant on Italy market Source: Reuters Industry Breifing Date: October 23, 2003
184 Antidepressants
•
GSK antidepressant gets FDA nod for social phobia. Source: Reuters Industry Breifing Date: October 17, 2003
•
Drop in adolescent suicide rates in US tied to rise in antidepressant use Source: Reuters Industry Breifing Date: October 13, 2003
•
Antidepressants seem to have reduced teen suicides Source: Reuters Health eLine Date: October 13, 2003
•
Genetic variation affect antidepressant side effects Source: Reuters Industry Breifing Date: October 06, 2003
•
Lilly says antidepressant needs no new trials Source: Reuters Industry Breifing Date: October 01, 2003
•
Antidepressants may improve survival after stroke Source: Reuters Health eLine Date: October 01, 2003
•
Antidepressant therapy reduces poststroke mortality Source: Reuters Industry Breifing Date: October 01, 2003
•
Antidepressant response rates do not differ by gender Source: Reuters Medical News Date: September 25, 2003
•
Increased antidepressant use linked to fall in suicide rates Source: Reuters Industry Breifing Date: September 24, 2003
•
Increased antidepressant use link to fall in suicide rates Source: Reuters Health eLine Date: September 24, 2003
•
Forest, Lundbeck sue Ivax on antidepressant copy Source: Reuters Industry Breifing Date: September 23, 2003
•
U.S. approves once-daily Glaxo antidepressant Source: Reuters Industry Breifing Date: August 29, 2003
•
U.S. approves Glaxo once-daily antidepressant, Wellbutrin XL Source: Reuters Medical News Date: August 29, 2003
•
Bristol in talks with Canada over antidepressant Source: Reuters Health eLine Date: August 29, 2003
•
Estradiol may have antidepressant effect in perimenopausal women Source: Reuters Industry Breifing Date: August 25, 2003
Periodicals and News
•
Antidepressants too widely prescribed in UK: report Source: Reuters Industry Breifing Date: August 22, 2003
•
CORRECTION: Antidepressants may benefit heart patients: study Source: Reuters Health eLine Date: August 12, 2003
•
Forest sees no antidepressant generic before 2011 Source: Reuters Industry Breifing Date: August 11, 2003
•
SSRI antidepressants may work by stimulating neurogenesis in hippocampus Source: Reuters Industry Breifing Date: August 08, 2003
•
Antidepressant therapy may curb binge eating Source: Reuters Health eLine Date: August 08, 2003
•
Ivax might get antidepressant earlier than expected. Source: Reuters Industry Breifing Date: August 07, 2003
•
Antidepressants grow new brain cells: U.S. study Source: Reuters Health eLine Date: August 07, 2003
•
Antidepressants may protect brain from damage Source: Reuters Health eLine Date: August 01, 2003
•
Antidepressants may prevent depression-related loss of hippocampal volume Source: Reuters Industry Breifing Date: August 01, 2003
•
Early discontinuation of antidepressants increases relapse risk in some bipolar patients Source: Reuters Industry Breifing Date: July 02, 2003
•
Disadvantaged women helped by antidepressants, too Source: Reuters Health eLine Date: July 01, 2003
•
Disadvantaged women benefit from antidepressants, counseling Source: Reuters Medical News Date: July 01, 2003
•
Antidepressant regimen aids bipolar disorder: study Source: Reuters Health eLine Date: July 01, 2003
•
FDA clears generic versions of Akzo Nobel antidepressant Source: Reuters Industry Breifing Date: June 19, 2003
•
Children shouldn't use Paxil antidepressant: FDA Source: Reuters Health eLine Date: June 19, 2003
185
186 Antidepressants
•
Ivax gets tentative U.S. approval for generic antidepressant Source: Reuters Industry Breifing Date: June 18, 2003
•
No clear link between antidepressants and breast cancer risk Source: Reuters Industry Breifing Date: June 17, 2003
•
Lundbeck wins Danish court case over generic antidepressant Source: Reuters Industry Breifing Date: June 17, 2003
•
Antidepressant helps relieve hot flashes: US study Source: Reuters Health eLine Date: June 03, 2003 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “antidepressants” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “antidepressants” (or synonyms). If you know the name of a company that is relevant to antidepressants, you can go to any stock trading Web site (such as http://www.etrade.com/)
Periodicals and News
187
and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “antidepressants” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “antidepressants” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on antidepressants: •
Antidepressants and Functional Gastrointestinal Disorders Source: Participate. 9(4): 1-3. Winter 2000. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail:
[email protected]. Website: www.iffgd.org. Summary: Antidepressants are commonly prescribed for the treatment of functional gastrointestinal (GI) disorders; they are unique drugs that have a number of properties that make them particularly useful. This article reviews three factors regarding antidepressants and functional GI disorders. The first is the mechanism of action of antidepressants, or how they exert their effect. The second is the relationship between the brain and the gut, also known as the 'brain gut axis.' Finally is the role of antidepressants in treating the various symptoms of functional GI disorders. The author first offers a history of the development of antidepressant drugs and their use for GI disorders, notably irritable bowel syndrome (IBS) and noncardiac chest pain (NCCP). Patients with IBS treated with the tricyclic desipramine (Norpramin) demonstrated improvement in their GI symptoms as well as a better sense of overall well being. Patients with NCCP on imipramine (Tofranil) reported a significant improvement in their gastrointestinal symptoms as well as improvement in their overall sense of well being. The author concludes with a brief discussion of the biopsychosocial model, where multiple dimensions of the patient's life, including gut function, overall well being, overall quality of life, and emotional status, are considered in patient treatment strategies. The use of dietary modification, antispasmodics, antidiarrheals, antidepressants, and behavioral interventions such as biofeedback, psychotherapy, and relaxation therapy all play a synergistic and important role in improving outcomes in functional gastrointestinal disorders. The author also stresses the importance of adequate patient education and patients participating as active members of their own health care team. One sidebar discusses the use of drugs based on serotonin for treating IBS.
188 Antidepressants
Academic Periodicals covering Antidepressants Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to antidepressants. In addition to these sources, you can search for articles covering antidepressants that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
189
CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for antidepressants. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with antidepressants. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
190 Antidepressants
following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to antidepressants: Anticonvulsants, Hydantoin •
Systemic - U.S. Brands: Cerebyx; Dilantin; Dilantin Infatabs; Dilantin Kapseals; Dilantin-125; Mesantoin; Peganone; Phenytex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202052.html
Antidepressants, Monoamine Oxidase (Mao) Inhibitor •
Systemic - U.S. Brands: Marplan; Nardil; Parnate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202054.html
Antidepressants, Tricyclic •
Systemic - U.S. Brands: Anafranil; Asendin; Aventyl; Elavil; Endep; Norfranil; Norpramin; Pamelor; Sinequan; Surmontil; Tipramine; Tofranil; Tofranil-PM; Vivactil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202055.html
Bupropion •
Systemic - U.S. Brands: Wellbutrin; Zyban http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202098.html
Chlordiazepoxide and Amitriptyline •
Systemic - U.S. Brands: Limbitrol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202129.html
Citalopram •
Systemic - U.S. Brands: Celexa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203653.html
Fluoxetine •
Systemic - U.S. Brands: Prozac; Sarafem http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202247.html
Fluvoxamine •
Systemic - U.S. Brands: Luvox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202919.html
Lithium •
Systemic - U.S. Brands: Cibalith-S; Eskalith; Lithane; Lithobid; Lithonate; Lithotabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202330.html
Loxapine •
Systemic - U.S. Brands: Loxitane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202333.html
Researching Medications
191
Maprotiline •
Systemic - U.S. Brands: Ludiomil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202337.html
Methylphenidate •
Systemic - U.S. Brands: Concerta; Ritalin; Ritalin-SR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202361.html
Mirtazapine •
Systemic - U.S. Brands: Remeron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203490.html
Nefazodone •
Systemic - U.S. Brands: Serzone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203491.html
Paroxetine •
Systemic - U.S. Brands: Paxil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202717.html
Perphenazine and Amitriptyline •
Systemic - U.S. Brands: Etrafon; Etrafon-A; Etrafon-Forte; Triavil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202453.html
Sertraline •
Systemic - U.S. Brands: Zoloft http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202651.html
Trazodone •
Systemic - U.S. Brands: Desyrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202573.html
Venlafaxine •
Systemic - U.S. Brands: Effexor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202764.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing
192 Antidepressants
information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
193
APPENDICES
195
APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
196 Antidepressants
•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
Physician Resources
197
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
198 Antidepressants
•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “antidepressants” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “antidepressants” (or synonyms) into the “For these words:” box. The following is a sample result: •
Revisiting IBS: Perspectives for the New Millennium: Special Report Source: New York, NY: McMahon Publishing Group. 2001. 8 p. Contact: Available from Gastroenterology and Endoscopy News. McMahon Publishing Group, 545 W. 45th St., 8th floor, New York, NY 10036 (800) 526-0828. Website: www.mcmahonmed.com. PRICE: $5.00 plus shipping and handling. Summary: Recent discoveries in the field of irritable bowel syndrome (IBS) have important implications for gastroenterologists. Research is underway into functional brain imaging techniques to assess activation of brain regions during visceral stimulation, as well as clinical examinations focusing on the relationship between infection and IBS. This report brings gastroenterologists and primary care practitioners up to date on the current approaches in drug therapy for patients with IBS. The authors explain the use of brain imaging techniques to understand how patients with IBS may be more sensitive to gut stimuli, discuss the theory that an acute outbreak of gastroenteritis may lead to long term chronic IBS, and discuss the latest treatment options that can be use for both IBS and the related abdominal pain and discomfort. Treatments for IBS are targeted to symptoms including abdominal pain, diarrhea, constipation, and bloating. The main choices for patients with pain predominant symptoms include antispasmodics, tricyclic antidepressants, and selective serotonic reuptake inhibitors (SSRIs), and 5HT3 antagonists and 5HT4 agonists. Patients with constipation predominant symptoms would be treated with fiber, laxatives, or 5HT4 agonists; for patients with diarrhea predominant symptoms, opioid agonists, 5HT3 antagonists, and possibly cholestyramine will be used. Each of these treatments is discussed, with the relevant literature briefly reviewed. A posttest is appended, with which readers can qualify for continuing education credits. References are provided in the text of the report.
•
Pharmocotherapy of Urge Incontinence Reviewed Source: in InConText. Management of the Incontinent Patient. Philadelphia, PA: CoMed Communications. 1990. p. 1, 3.
Physician Resources
199
Contact: Available from CoMed Communications. 210 West Washington Square, Philadelphia, PA 19106. (215) 592-1363. PRICE: Free. Summary: This report developed from a presentation at the symposium, 'Pharmacotherapy for Urge Incontinence,' held March 17, 1990 in Miami, Florida, reviews the drugs used to treat storage failure secondary to either bladder hyperactivity or bladder hypersensitivity. The following classes of drugs are discussed: the anticholinergics; antispasmodics or musculotropic relaxants; calcium antagonists; and tricyclic antidepressants. In addition, specific drugs including oxybutynin, propantheline, dicyclomine, terodiline, and phenazopyridine, are mentioned. The article concludes that sphincter incontinence is best treated pharmacologically with alphaadrenergic agonists. Finally, estrogen is noted as a useful adjunct therapy for postmenopausal women. •
Osteoarthritis of the Knee: A Special Report Source: Physician and Sportsmedicine. Special Report. May 2000. Contact: Available from McGraw-Hill Healthcare Information. 4530 West 77th Street, Floor 3, Minneapolis, MN 55435. (800) 525-5003 or (609) 426-7070 (for subscriptions) or (952) 835-3222 (for back issues). Summary: This special report presents a series of articles that provide health professionals with information on osteoarthritis (OA) of the knee. The first article reviews the pathophysiological characteristics of OA and discusses its etiology, diagnosis, and evaluation. OA is caused by multiple factors, including genetic, metabolic, biochemical, enzymatic, biomechanical, and environmental factors. The history, physical examination, and radiographic examination help establish the diagnosis. The second article offers an overview of the nonoperative management of OA of the knee. Nonoperative techniques can be effective in relieving pain and improving functional ability. Nonpharmacologic treatment options include decreasing physical activity, exercising, losing weight, using supports and braces, and undergoing physiotherapy. Topical treatments include nonsteroidal anti-inflammatory drugs (NSAIDs) and capsaicin. Systemic therapies include nonnarcotic and narcotic analgesics, antidepressants, NSAIDs, chondroitin, and glucosamine. Intra-articular therapies include corticosteroids and viscosupplementation. The third article discusses operative treatment for the arthritic knee, focusing on the role of arthroscopy, the indications for joint replacement, and the new area of articular cartilage restoration and resurfacing. The choice of procedure is based on the patient's age, the extent of disease, and the desired level of physical activity. The fourth article presents case reports of active patients with arthritis who underwent viscosupplementation. The fifth article uses a question and answer format to provide health professionals with information on traditional and innovative treatments for OA of the knee. The final article is a continuing medical education activity. 5 tables and 95 references.
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface,
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
200 Antidepressants
providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “antidepressants” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 40653 396 1006 106 56 42217
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “antidepressants” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
19
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story.
Physician Resources
201
more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
22
After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
203
APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on antidepressants can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to antidepressants. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to antidepressants. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “antidepressants”:
204 Antidepressants
•
Other guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Child Mental Health http://www.nlm.nih.gov/medlineplus/childmentalhealth.html Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.html Mental Health http://www.nlm.nih.gov/medlineplus/mentalhealth.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on antidepressants. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Interstitial Cystitis and Tricyclic Antidepressants Source: Rockville, MD: Interstitial Cystitis Association. 2001. 1 p. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail:
[email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFA01. Summary: This fact sheet reviews the use of tricyclic antidepressants for treating patients who have interstitial cystitis (IC). IC is characterized by a number of symptoms (urinary urgency, frequency, suprapubic pain, diminished bladder capacity) which can affect IC patients in varying combinations or in varying degrees of intensity. When treating IC patients with tricyclic antidepressants, physicians are not seeking to treat depression. Instead, they are using these medications for their beneficial side effects, which have been shown to help IC as well as other chronic pain conditions. In smaller doses than those necessary to treat depression, these drugs help IC by blocking pain, calming bladder spasms, and reducing inflammation. The fact sheet outlines treatment using tricyclic antidepressants, lists the most common brand and generic names used, lists the most common side effects, and offers strategies to cope with unwanted side effects of the medications. The fact sheet includes the contact information for the Interstitial Cystitis Association (ICA). 4 references. (AA-M).
Patient Resources
•
205
Antidepressants for Cyclic Vomiting Syndrome Source: Canal Winchester, OH: Cyclic Vomiting Syndrome Association, USA/Canada. 2002. [3 p]. Contact: Available from Cyclic Vomiting Syndrome Association, USA/Canada. 3585 Cedar Hill Road, NW, Canal Winchester, OH 43110. (614) 837-2586. Fax (614) 837-2586. E-mail:
[email protected]. Website: www.cvsaonline.org. PRICE: Single copy free. Summary: This newsletter article discusses the use of antidepressants in the treatment of cyclic vomiting in mitochondrial disease. Cyclic vomiting refers to discrete and severe episodes of vomiting, nausea, and lethargy (severe tiredness). Episodes are discrete in that the sufferer is free of nausea and vomiting between episodes. Episodes can occur on a routine schedule, be triggered by physical or psychological stress, or appear to come at random. Cyclic vomiting has many known causes, including intestinal blockage, brain disorders, kidney disease, and several different metabolic disorders. Many of these causes are treatable, so a careful diagnostic work up is important. However, in the vast majority of cases, none of the above causes can be found, and these individuals are given the diagnosis of cyclic vomiting syndrome (CVS). Antidepressants are particularly useful in controlling functional symptoms in conditions including irritable bowel syndrome, functional dyspepsia, and fibromyalgia. Benefits on the physical symptoms can be independent of the drugs' psychiatric effects. The tricyclic antidepressants (TCAs), such as amitriptyline, nortriptyline, or desipramine, appear particularly useful, even in low daily dosages that would be considered subtherapeutic from the psychiatric standpoint. No single TCA has surfaced as superior to the other for CVS, although amitriptyline is most often utilized. The author offers guidelines for administration and dosage, patient selection, and coping with side effects of these drugs. 1 figure. 9 references. The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to antidepressants. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
206 Antidepressants
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to antidepressants. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with antidepressants. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about antidepressants. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “antidepressants” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “antidepressants”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For
Patient Resources
207
publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “antidepressants” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “antidepressants” (or a synonym) into the search box, and click “Submit Query.”
209
APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
23
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
210 Antidepressants
libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
24
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries
211
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
212 Antidepressants
•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
213
•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
214 Antidepressants
•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
215
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on antidepressants: •
Basic Guidelines for Antidepressants Antidepressants overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002511.htm
•
Signs & Symptoms for Antidepressants Agitation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Blurred vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm
216 Antidepressants
Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Incoordination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm Irregular heartbeat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Loss of consciousness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Muscle rigidity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Restlessness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Stupor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Urinary hesitancy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003143.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •
Diagnostics and Tests for Antidepressants Abnormal body temperature Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003400.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm
•
Background Topics for Antidepressants Breathing slow and labored Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000007.htm
Online Glossaries 217
Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Shock Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000039.htm Vital signs Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002341.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
219
ANTIDEPRESSANTS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 2-Propanol: An isomer of 1-propanol. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acyl: Chemical signal used by bacteria to communicate. [NIH]
220 Antidepressants
Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adolescent Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders in individuals 13-18 years. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic
Dictionary 221
metabolism. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agnosia: Loss of the ability to comprehend the meaning or recognize the importance of various forms of stimulation that cannot be attributed to impairment of a primary sensory modality. Tactile agnosia is characterized by an inability to perceive the shape and nature of an object by touch alone, despite unimpaired sensation to light touch, position, and other primary sensory modalities. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+
222 Antidepressants
and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]
Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alprostadil: A potent vasodilator agent that increases peripheral blood flow. It inhibits platelet aggregation and has many other biological effects such as bronchodilation, mediation of inflammation, etc. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Amenorrhea: Absence of menstruation. [NIH]
Dictionary 223
Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyotrophy: A type of diabetic neuropathy that causes muscle weakness and wasting. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but
224 Antidepressants
shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anecdotal report: An incomplete description of the medical and treatment history of one or more patients. Anecdotal reports may be published in places other than peer-reviewed, scientific journals. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms.
Dictionary 225
[NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antidiarrheals: Miscellaneous agents found useful in the symptomatic treatment of diarrhea. They have no effect on the agent(s) that cause diarrhea, but merely alleviate the condition. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH]
226 Antidepressants
Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the
Dictionary 227
diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appetitive Behavior: Animal searching behavior. The variable introductory phase of an instinctive behavior pattern or sequence, e.g., looking for food, or sequential courtship patterns prior to mating. [NIH] Apraxia: Loss of ability to perform purposeful movements, in the absence of paralysis or sensory disturbance, caused by lesions in the cortex. [NIH] Aptitude: The ability to acquire general or special types of knowledge or skill. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arcuate Nucleus: A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Argipressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, cyclic 1-6 disulfide. The usual mammalian antidiuretic hormone, it is a cyclic nonapeptide with arginine in position 8 of the chain. Argipressin is used to treat diabetes insipidus and as hemostatic because of its vasoconstrictor action. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH]
228 Antidepressants
Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Athetosis: A derangement marked by ceaseless occurrence of slow, sinuous, writhing movements, especially severe in the hands, and performed involuntarily; it may occur after hemiplegia, and is then known as posthemiplegic chorea. Called also mobile spasm. [EU] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also
Dictionary 229
called visceral neuropathy. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Avian: A plasmodial infection in birds. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the
230 Antidepressants
treatment of behavior disorders. [NIH] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzamides: Benzoic acid amides. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Benztropine: A centrally active muscarinic antagonist that has been used in the symptomatic treatment of Parkinson's disease. Benztropine also inhibits the uptake of dopamine. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Betahistine: N-Methyl-2-pyridineethanamine. A physiological histamine analog vasodilator agent that also acts as a histamine H1 receptor agonist. It is used in Meniere's disease and in vascular headaches but may exacerbate bronchial asthma and peptic ulcers. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural
Dictionary 231
amino acids. [NIH] Biological Factors: Compounds made by living organisms that contribute to or influence a phenomenon or process. They have biological or physiological activities. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blepharospasm: Excessive winking; tonic or clonic spasm of the orbicularis oculi muscle. [NIH]
Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose.
232 Antidepressants
[NIH]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulking Agents: Laxatives that make bowel movements soft and easy to pass. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU]
Dictionary 233
Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal
234 Antidepressants
seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiotonic Agents: Agents that have a tonic effect on the heart or increase cardiac output. They may be glycosidic steroids related to Digitalis products, sympathomimetics, or other drugs and are used after myocardial infarcts, cardiac surgery, in shock, or in congestive heart failure. [NIH] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship
Dictionary 235
of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Central Nervous System Stimulants: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. [NIH]
236 Antidepressants
Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Child Behavior: Any observable response or action of a child from 24 months through 12 years of age. For neonates or children younger than 24 months, infant behavior is available. [NIH]
Child Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders in children. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chloral Hydrate: A hypnotic and sedative used in the treatment of insomnia. The safety
Dictionary 237
margin is too narrow for chloral hydrate to be used as a general anesthetic in humans, but it is commonly used for that purpose in animal experiments. It is no longer considered useful as an anti-anxiety medication. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]
Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (paraganglia, chromaffin) of the sympathetic nervous system. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH]
238 Antidepressants
Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]
Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clomipramine: A tricyclic antidepressant similar to imipramine that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. [NIH]
Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with
Dictionary 239
administration of this agent. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Colitis: Inflammation of the colon. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH]
240 Antidepressants
Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine.
Dictionary 241
Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continence: The ability to hold in a bowel movement or urine. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH]
242 Antidepressants
Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance;
Dictionary 243
and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Courtship: The mutual attraction between individuals of the opposite sex. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Criterion: A standard by which something may be judged. [EU] Cromolyn Sodium: A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Cryostat: A batchwise operating apparatus in which a cryogenic liquid or solid is used to maintain by evaporation a cryotemperature which needs not be constant but may vary in a predetermined fashion. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclic Vomiting Syndrome: Sudden, repeated attacks of severe vomiting (especially in children), nausea, and physical exhaustion with no apparent cause. Can last from a few hours to 10 days. The episodes begin and end suddenly. Loss of fluids in the body and changes in chemicals in the body can require immediate medical attention. Also called abdominal migraine. [NIH] Cyproheptadine: A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom
244 Antidepressants
of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defecation: The normal process of elimination of fecal material from the rectum. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH]
Dictionary 245
Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Desmopressin: A synthetic analog of the natural hormone 8-arginine vasopressin (argipressin). Its action is mediated by the vasopressin receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating factor
246 Antidepressants
VIII and von Willebrand factor. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Dicyclomine: A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Diffusion of Innovation: The broad dissemination of new ideas, procedures, techniques, materials, and devices and the degree to which these are accepted and used. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH]
Dictionary 247
Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulfiram: A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. [NIH] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several
248 Antidepressants
systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [NIH] Dopamine Antagonists: Drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and for hiccup. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Costs: The amount that a health care institution or organization pays for its drugs. It is one component of the final price that is charged to the consumer (fees, pharmaceutical or prescription fees). [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH]
Dictionary 249
Duct: A tube through which body fluids pass. [NIH] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]
symptoms
resulting
from
an
absent
or
Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one replacement in the same or a new environment. The embryo is usually phase, i.e., a blastocyst. The process includes embryo or blastocyst transfer after in vitro fertilization and transfer of the inner cell mass of
environment and in the pre-nidation transplantation or the blastocyst. It is
250 Antidepressants
not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emetic: An agent that causes vomiting. [EU] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endolymphatic Duct: Duct connecting the endolymphatic sac with the membranous labyrinth. [NIH] Endolymphatic Sac: The blind pouch at the end of the endolymphatic duct. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH]
Dictionary 251
Endotoxin: Toxin from cell walls of bacteria. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Enhancer: Transcriptional element in the virus genome. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bed-wetting, nocturnal enuresis). [EU] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH]
252 Antidepressants
Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Euphoria: An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence
Dictionary 253
of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such
254 Antidepressants
as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fludrocortisone: A synthetic mineralocorticoid with anti-inflammatory activity. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluphenazine: A phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Formularies: Lists of drugs or collections of recipes, formulas, and prescriptions for the compounding of medicinal preparations. Formularies differ from pharmacopoeias in that they are less complete, lacking full descriptions of the drugs, their formulations, analytic composition, chemical properties, etc. In hospitals, formularies list all drugs commonly stocked in the hospital pharmacy. [NIH] Formulary: A book containing a list of pharmaceutical products with their formulas and means of preparation. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]
Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Frozen Sections: Thinly cut sections of frozen tissue specimens prepared with a cryostat or
Dictionary 255
freezing microtome. [NIH] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrectomy: An operation to remove all or part of the stomach. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
256 Antidepressants
Gastritis: Inflammation of the stomach. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids
Dictionary 257
(steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosuria: The presence of glucose in the urine; especially the excretion of an abnormally large amount of sugar (glucose) in the urine, i.e., more than 1 gm. in 24 hours. [EU] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of
258 Antidepressants
the limbic system. [NIH] Haematemesis: The vomiting of blood. [EU] Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hallucination: A sense perception without a source in the external world; a perception of an external stimulus object in the absence of such an object. [EU] Hallucinogens: Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. [NIH] Haloperidol: Butyrophenone derivative. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hearing aid: A miniature, portable sound amplifier for persons with impaired hearing, consisting of a microphone, audio amplifier, earphone, and battery. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH]
Dictionary 259
Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoperfusion: Removal of toxins or metabolites from the circulation by the passing of blood, within a suitable extracorporeal circuit, over semipermeable microcapsules containing adsorbents (e.g., activated charcoal) or enzymes, other enzyme preparations (e.g., gel-entrapped microsomes, membrane-free enzymes bound to artificial carriers), or other adsorbents (e.g., various resins, albumin-conjugated agarose). [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
260 Antidepressants
Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydroalcoholic: Of or relating to water and alcohol. [EU] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. [NIH]
Dictionary 261
Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperglycaemia: Abnormally increased content of sugar in the blood. [EU] Hyperglycemia: Abnormally high blood sugar. [NIH] Hypericum: Genus of perennial plants in the family Clusiaceae (Hypericaceae). Herbal and homeopathic preparations are used for depression, neuralgias, and a variety of other conditions. Contains flavonoids, glycosides, mucilage, tannins, and volatile oils (oils, essential). [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypnotherapy: Sleeping-cure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the
262 Antidepressants
result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]
Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impaction: The trapping of an object in a body passage. Examples are stones in the bile duct or hardened stool in the colon. [NIH]
Dictionary 263
Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant Behavior: Any observable response or action of a neonate or infant up through the age of 23 months. [NIH] Infant Care: Care of infants in the home or institution. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon
264 Antidepressants
and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interindividual: Occurring between two or more individuals. [EU] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH]
Dictionary 265
Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraindividual: Being or occurring within the individual. [EU] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction
266 Antidepressants
of a blood vessel. [EU] Isethionic Acid: A colorless, syrupy, strongly acidic liquid that can form detergents with oleic acid. [NIH] Islet: Cell producing insulin in pancreas. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Language Development Disorders: Conditions characterized by language abilities (comprehension and expression of speech and writing) that are below the expected level for a given age, generally in the absence of an intellectual impairment. These conditions may be associated with deafness; brain diseases; mental disorders; or environmental factors. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Language Therapy: Rehabilitation of persons with language disorders or training of
Dictionary 267
children with language development disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities
268 Antidepressants
of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Lithium Carbonate: A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of biogenic monoamines in the central nervous system, and affects multiple neurotransmission systems. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH]
Dictionary 269
Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH]
270 Antidepressants
Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Maternal Deprivation: Prolonged separation of the offspring from the mother. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH]
Dictionary 271
Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Health Services: Organized services to provide mental health care. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic
272 Antidepressants
cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mianserin: A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired
Dictionary 273
from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief
274 Antidepressants
constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH]
Dictionary 275
Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Neck Muscles: The neck muscles consist of the platysma, splenius cervicis, sternocleidomastoid(eus), longus colli, the anterior, medius, and posterior scalenes, digastric(us), stylohyoid(eus), mylohyoid(eus), geniohyoid(eus), sternohyoid(eus), omohyoid(eus), sternothyroid(eus), and thyrohyoid(eus). [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH]
276 Antidepressants
Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH]
Dictionary 277
Neurotrophins: A nerve growth factor. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonulcer Dyspepsia: Constant pain or discomfort in the upper GI tract. Symptoms include burning, nausea, and bloating, but no ulcer. Possibly caused by muscle spasms. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normetanephrine: A methylated metabolite of norepinephrine that is excreted in the urine and found in certain tissues. It is a marker for tumors. [NIH] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]
278 Antidepressants
Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Octopamine: An alpha-adrenergic sympathomimetic amine, biosynthesized from tyramine in the CNS and platelets and also in invertebrate nervous systems. It is used to treat hypotension and as a cardiotonic. The natural D(-) form is more potent than the L(+) form in producing cardiovascular adrenergic responses. It is also a neurotransmitter in some invertebrates. [NIH] Oculi: Globe or ball of the eye. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Management: Planning, organizing, and administering activities in an office. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the
Dictionary 279
lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossicles: The hammer, anvil and stirrup, the small bones of the middle ear, which transmit the vibrations from the tympanic membrane to the oval window. [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Otosclerosis: The formation of spongy bone in the labyrinth capsule. The ossicles can become fixed and unable to transmit sound vibrations, thereby causing deafness. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic
280 Antidepressants
metabolism. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsies: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paraganglia, Chromaffin: Small bodies containing chromaffin cells occurring outside of the adrenal medulla, most commonly near the sympathetic ganglia and in organs such as the kidney, liver, heart and gonads. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasympathetic Nervous System: The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. [NIH] Parasympathomimetics: Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (cholinesterase inhibitors). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (ganglionic stimulants) are not included here. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU]
Dictionary 281
Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]
Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentosan polysulfate: A drug used to relieve pain or discomfort associated with chronic inflammation of the bladder. It is also being evaluated for its protective effects on the gastrointestinal tract in people undergoing radiation therapy. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH]
282 Antidepressants
Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perennial: Lasting through the year of for several years. [EU] Pergolide: A long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. [NIH]
Perilymph: The fluid contained within the space separating the membranous from the osseous labyrinth of the ear. [NIH] Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Perioral: Situated or occurring around the mouth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use,
Dictionary 283
they do not fall into another group of products. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacopoeias: Authoritative treatises on drugs and preparations, their description, formulation, analytic composition, physical constants, main chemical properties used in identification, standards for strength, purity, and dosage, chemical tests for determining identity and purity, etc. They are usually published under governmental jurisdiction (e.g., USP, the United States Pharmacopoeia; BP, British Pharmacopoeia; P. Helv., the Swiss Pharmacopoeia). They differ from formularies in that they are far more complete: formularies tend to be mere listings of formulas and prescriptions. [NIH] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenazopyridine: A local anesthetic that has been used in urinary tract disorders. Its use is limited by problems with toxicity (primarily blood disorders) and potential carcinogenicity. [NIH]
Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and
284 Antidepressants
function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene
Dictionary 285
changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polyneuropathies: Diseases of multiple peripheral nerves. The various forms are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH]
286 Antidepressants
Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH]
Dictionary 287
Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prescription Fees: The charge levied on the consumer for drugs or therapy prescribed under written order of a physician or other health professional. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Health Services: Services designed for promotion of health and prevention of disease. [NIH] Primary tumor: The original tumor. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU]
288 Antidepressants
Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Propantheline: A muscarinic antagonist used as an antispasmodic, in rhinitis, in urinary incontinence, and in the treatment of ulcers. At high doses it has nicotinic effects resulting in neuromuscular blocking. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH]
Dictionary 289
Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man
290 Antidepressants
and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH]
Dictionary 291
Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that
292 Antidepressants
the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]
Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU]
Dictionary 293
Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Personnel: Those individuals engaged in research. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retrospective study: A study that looks backward in time, usually using medical records
294 Antidepressants
and interviews with patients who already have or had a disease. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rolipram: A phosphodiesterase inhibitor with antidepressant properties. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH]
Dictionary 295
Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU]
296 Antidepressants
Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotonin Agonists: Agents that have an affinity for serotonin receptors and are able to mimic the effects of serotonin by stimulating the physiologic activity at the cell receptors. These compounds are used as antidepressants, anxiolytics, and in the treatment of migraine. [NIH]
Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonin agonists. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter)
Dictionary 297
is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a
298 Antidepressants
major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH]
Dictionary 299
Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by
300 Antidepressants
clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At
Dictionary 301
classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telecommunications: Transmission of information over distances via electronic means. [NIH]
Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tendinitis: Inflammation of tendons and of tendon-muscle attachments. [EU] Tenosynovitis: Inflammation of a tendon sheath. [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used
302 Antidepressants
mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory
Dictionary 303
innervation to parts of the calf and foot. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]
Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Torticollis: Wryneck; a contracted state of the cervical muscles, producing twisting of the neck and an unnatural position of the head. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheotomy: Surgical incision of the trachea. [NIH] Traction: The act of pulling. [NIH]
304 Antidepressants
Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trifluoperazine: A phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU]
Dictionary 305
Trimipramine: Tricyclic antidepressant similar to imipramine, but with more antihistaminic and sedative properties. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Underachievement: Performance, usually in school work, poorer than that predicted from aptitude and/or intelligence testing. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urinary urgency: Inability to delay urination. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in
306 Antidepressants
the bladder, and leaves the body through the urethra. [NIH] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Urologist: A doctor who specializes in diseases of the urinary organs in females and the urinary and sex organs in males. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Headaches: A group of disorders characterized by recurrent headaches associated with abnormal dilation and constriction of cerebral blood vessels. Representative disorders from this category include migraine, cluster headache, and paroxysmal hemicrania. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the
Dictionary 307
substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibular Nerve: The vestibular part of the 8th cranial nerve (vestibulocochlear nerve). The vestibular nerve fibers arise from neurons of Scarpa's ganglion and project peripherally to vestibular hair cells and centrally to the vestibular nuclei of the brain stem. These fibers mediate the sense of balance and head position. [NIH] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and
308 Antidepressants
kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vocal cord: The vocal folds of the larynx. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Watchful waiting: Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called observation. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH]
Dictionary 309
X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
311
INDEX 2 2-Propanol, 149, 219 A Abdomen, 167, 219, 231, 232, 251, 265, 268, 299, 302, 306, 308 Abdominal, 4, 165, 167, 169, 171, 172, 198, 219, 243, 246, 256, 265, 280, 287, 305 Abdominal Pain, 4, 167, 169, 171, 172, 198, 219, 256, 265, 305 Aberrant, 32, 219 Acceptor, 219, 279, 300, 304 Acetaldehyde, 30, 219, 247 Acetaminophen, 21, 219 Acetone, 219 Acetylcholine, 148, 219, 237, 277, 280 Acetyltransferases, 144, 219 Acidosis, 156, 219 Acne, 219, 293 Acoustic, 172, 219, 307 Activities of Daily Living, 177, 219 Acute Disease, 165, 219 Acute leukemia, 219, 302 Acyl, 126, 219 Adaptation, 24, 55, 220, 237, 284 Adenine, 220, 290 Adenosine, 17, 73, 220, 233, 261, 284 Adenosine Monophosphate, 73, 220 Adenylate Cyclase, 83, 85, 89, 92, 220, 254 Adjunctive Therapy, 146, 220 Adjustment, 14, 31, 58, 220 Adjuvant, 13, 20, 37, 220 Adjuvant Therapy, 20, 220 Adolescent Psychiatry, 44, 72, 220 Adrenal Cortex, 220, 242, 287 Adrenal Medulla, 220, 235, 237, 251, 277, 280 Adrenergic Agonists, 173, 174, 176, 199, 220 Adrenergic Antagonists, 176, 220 Adverse Effect, 18, 22, 121, 172, 180, 220, 227, 238, 296 Aerobic, 220, 279 Aerobic Metabolism, 220, 221, 280 Aerobic Respiration, 220, 279 Afferent, 35, 140, 167, 173, 221, 243, 284, 286, 296 Affinity, 21, 32, 56, 71, 87, 93, 127, 136, 149, 221, 228, 238, 245, 246, 268, 296, 297
Agar, 221, 284 Agarose, 221, 259 Age of Onset, 221, 305 Aggressiveness, 87, 93, 221 Agnosia, 177, 221 Agonist, 7, 30, 82, 86, 87, 89, 93, 147, 148, 221, 226, 230, 232, 248, 274, 277, 282 Agoraphobia, 221, 262, 280, 283 Akathisia, 221, 226 Albumin, 221, 259 Aldehyde Dehydrogenase, 144, 221, 247 Aldehydes, 222, 308 Alertness, 222, 233, 235 Algorithms, 222, 231 Alimentary, 222, 266, 281 Alkaline, 219, 222, 223, 233 Alkaloid, 222, 228, 232, 233, 239, 273, 277, 291, 295 Allergen, 222, 245, 296 Allylamine, 222, 223 Alpha Particles, 222, 291 Alpha-1, 12, 222, 223 Alprostadil, 170, 222 Alternative medicine, 186, 222 Alternative Splicing, 6, 222, 289 Aluminum, 222, 300 Amantadine, 175, 222 Amebiasis, 222, 271 Amenorrhea, 222, 232 Amine, 24, 36, 47, 140, 146, 223, 230, 260, 278 Amino Acid Sequence, 223, 225, 252 Amino Acids, 36, 46, 134, 223, 230, 231, 234, 252, 276, 281, 285, 289, 296, 300, 304 Amitriptyline, 134, 166, 168, 171, 190, 191, 205, 223 Ammonia, 223 Amnestic, 223, 254 Amphetamine, 18, 46, 47, 223, 230, 246 Amplification, 132, 143, 223 Amygdala, 23, 223, 229, 268, 296, 302 Amyotrophy, 141, 223 Anaesthesia, 223, 263 Anal, 223, 254, 269, 283 Analgesic, 4, 6, 13, 66, 134, 147, 148, 219, 223, 239, 267, 273, 278, 291 Analog, 17, 25, 223, 230, 245, 246, 266 Analogous, 130, 223, 248, 304
312 Antidepressants
Anaphylatoxins, 223, 240 Anatomical, 101, 224, 228, 250, 263, 276 Androgens, 220, 224, 243 Anecdotal report, 3, 224 Anesthesia, 70, 72, 133, 138, 151, 168, 224, 243, 287 Anesthetics, 13, 56, 79, 135, 138, 151, 169, 175, 224, 229, 251 Angina, 224, 288 Angina Pectoris, 224, 288 Anginal, 224, 277 Angiotensin converting enzyme inhibitor, 131, 156, 224 Animal model, 8, 12, 13, 26, 29, 48, 98, 148, 224 Annealing, 224, 285 Anorectal, 4, 224 Anorexia, 105, 145, 151, 224, 256 Antagonism, 82, 88, 224, 233, 238 Antiallergic, 224, 243 Anti-Anxiety Agents, 224, 287, 290, 304 Antibacterial, 224, 298 Antibiotic, 73, 224, 252, 287, 298, 301 Antibodies, 7, 53, 57, 61, 225, 258, 272, 273, 284 Antibody, 221, 225, 232, 240, 258, 260, 262, 263, 265, 270, 273, 291, 296, 298, 309 Anticholinergic, 9, 64, 129, 166, 167, 169, 173, 174, 176, 223, 225, 236 Anticoagulant, 225, 289 Anticonvulsant, 84, 90, 126, 225, 233 Antidepressive Agents, 225, 290 Antidiarrheals, 4, 169, 187, 225 Antidiuretic, 173, 176, 225, 227, 245 Antiemetic, 225, 226, 237, 260, 271, 304 Antiepileptic, 16, 19, 225 Antifungal, 225, 266 Antigen, 221, 225, 240, 260, 261, 262, 263, 270, 296 Antigen-Antibody Complex, 225, 240 Antihypertensive, 225, 254, 282 Anti-inflammatory, 31, 131, 157, 166, 199, 219, 225, 228, 243, 254, 257, 294 Anti-Inflammatory Agents, 166, 225, 228, 243 Antimetabolite, 225, 302 Antineoplastic, 226, 243, 302 Antipruritic, 226, 237, 243 Antipsychotic, 9, 14, 33, 34, 69, 165, 174, 226, 237, 238, 248, 276, 294, 304 Antipsychotic Agents, 226, 248, 304 Antipyretic, 219, 226, 291
Antiseptic, 219, 226 Antispasmodic, 6, 226, 246, 278, 288, 295 Antitussive, 226, 246, 278 Antiviral, 222, 226, 275 Anus, 223, 224, 226, 232, 282 Anxiety Disorders, 34, 49, 86, 93, 144, 165, 226, 280 Anxiolytic, 33, 63, 100, 151, 226 Aorta, 226, 242, 307 Apathy, 226, 276 Aphasia, 177, 223, 226 Apomorphine, 87, 93, 226 Apoptosis, 20, 227 Appetitive Behavior, 48, 227 Apraxia, 177, 227 Aptitude, 227, 305 Aqueous, 99, 134, 227, 229, 244, 250 Arachidonate 12-Lipoxygenase, 227, 268 Arachidonate 15-Lipoxygenase, 227, 268 Arachidonate Lipoxygenases, 227, 268 Arachidonic Acid, 227, 267, 268, 288 Arcuate Nucleus, 83, 89, 227 Arginine, 55, 169, 223, 227, 245, 277 Argipressin, 227, 245 Aromatic, 128, 132, 227, 230, 234, 283 Arterial, 222, 227, 242, 261, 289, 301 Arteries, 226, 227, 231, 242, 272, 274, 290, 305 Arterioles, 227, 231 Arthroscopy, 199, 228 Articular, 199, 228, 267, 279 Aspartate, 136, 140, 228, 246 Aspergillosis, 228, 266 Aspirin, 156, 172, 228 Assay, 25, 47, 129, 130, 148, 228 Astrocytes, 228, 273 Asymptomatic, 62, 222, 228 Athetosis, 174, 228 Atrial, 228, 242, 304 Atrioventricular, 228, 242 Atrium, 82, 88, 228, 242, 304, 307 Atrophy, 43, 228 Atropine, 169, 228, 230, 295 Attenuation, 30, 228 Atypical, 5, 9, 11, 14, 33, 69, 139, 140, 146, 163, 228, 238, 277, 294 Auditory, 177, 228, 258, 270, 286, 306 Autonomic, 7, 38, 131, 137, 141, 175, 219, 226, 228, 230, 243, 277, 280, 282, 285, 298, 300 Autonomic Nervous System, 131, 175, 228, 230, 280, 282, 298, 300
Index 313
Autonomic Neuropathy, 141, 228 Autoradiography, 7, 17, 52, 61, 229 Autosuggestion, 229, 261 Avian, 153, 229 Axonal, 229, 285 Axons, 53, 229, 245, 275, 278, 282, 287, 290 B Babesiosis, 229, 291 Back Pain, 120, 229 Bacteria, 219, 224, 225, 229, 241, 245, 251, 252, 253, 255, 272, 298, 304, 305, 306 Bacterial Physiology, 220, 229 Bactericidal, 229, 252 Bacteriophage, 229, 284, 304 Bacteriostatic, 229, 252 Bacterium, 229, 241 Barbiturate, 229, 242 Basal Ganglia, 226, 229, 237, 255, 268, 278 Basal Ganglia Diseases, 229, 237 Base, 31, 128, 150, 220, 229, 244, 245, 266, 285, 290, 301 Basophils, 229, 257, 267 Behavior Therapy, 229 Behavioral Symptoms, 180, 230 Belladonna, 228, 230 Benign, 9, 48, 230, 255, 258, 291 Benzamides, 146, 230 Benzene, 230 Benzodiazepines, 75, 126, 129, 147, 148, 175, 177, 180, 181, 230 Benzoic Acid, 169, 230 Benztropine, 120, 230 Beta blocker, 177, 230 Betahistine, 172, 230 Bile, 230, 237, 255, 256, 262, 268, 299, 300 Bile Acids, 230, 256, 299, 300 Bile Ducts, 230 Biliary, 167, 230, 233, 237, 246 Biliary Tract, 167, 230, 233 Binding Sites, 36, 61, 230 Bioavailability, 84, 90, 142, 230 Biochemical, 7, 26, 33, 35, 52, 55, 98, 163, 199, 225, 230, 231, 279, 296 Biogenic Amines, 171, 230 Biogenic Monoamines, 230, 268 Biological Factors, 137, 231 Biological Transport, 231, 246 Biopsy, 158, 179, 231 Biosynthesis, 227, 231, 254, 289, 296 Biotechnology, 62, 65, 163, 186, 197, 231 Bipolar Disorder, 29, 34, 36, 39, 66, 70, 77, 100, 105, 165, 185, 204, 231
Blastocyst, 231, 241, 249, 284 Blastomycosis, 231, 266 Blepharospasm, 174, 231 Bloating, 4, 173, 198, 231, 256, 263, 265, 277 Blood Cell Count, 121, 231, 259 Blood Coagulation, 231, 233, 302 Blood Platelets, 231, 296 Blood pressure, 5, 166, 170, 216, 225, 231, 234, 236, 261, 266, 273, 277, 290, 297 Blood-Brain Barrier, 231, 267 Blot, 17, 61, 231, 262 Blotting, Western, 232, 262 Body Fluids, 232, 249, 297 Bone Marrow, 219, 230, 232, 262, 269, 273 Bone scan, 232, 294 Bowel, 4, 5, 152, 165, 167, 169, 223, 232, 241, 246, 264, 265, 267, 299, 305 Bowel Movement, 232, 241, 246, 299 Brachytherapy, 232, 264, 265, 291, 309 Bradykinin, 232, 277 Brain Stem, 62, 131, 232, 236, 242, 280, 307 Branch, 83, 89, 213, 232, 249, 256, 269, 270, 276, 281, 290, 298, 300, 302 Breakdown, 24, 232, 246, 255, 280 Bromocriptine, 175, 232 Bronchi, 232, 251, 266, 303 Bronchial, 230, 232, 260 Bronchodilator, 232, 266 Buccal, 31, 232 Bulking Agents, 171, 232 Bupivacaine, 56, 232, 267 Bupropion, 65, 73, 109, 121, 190, 232 Bursitis, 175, 232 C Caffeine, 21, 147, 148, 172, 233, 290 Calcineurin, 23, 233 Calcium, 35, 55, 56, 148, 156, 166, 168, 169, 170, 171, 173, 176, 199, 233, 238, 240, 277, 297 Calcium channel blocker, 56, 156, 166, 169, 170, 171, 233 Calcium Channel Blockers, 56, 156, 166, 169, 170, 171, 233 Calculi, 233, 257 Calmodulin, 23, 35, 55, 233 Candidiasis, 76, 233 Candidosis, 233 Capsaicin, 147, 148, 156, 170, 199, 233 Capsules, 233, 248 Carbamazepine, 169, 172, 233 Carbohydrate, 130, 141, 234, 242
314 Antidepressants
Carbon Dioxide, 32, 174, 234, 244, 254, 284, 293, 306 Carboxy, 234 Carboxylic Acids, 128, 234 Carcinogen, 234, 272 Carcinogenesis, 60, 234 Carcinogenic, 230, 234, 264, 299 Cardiac, 34, 58, 140, 157, 222, 233, 234, 238, 242, 250, 251, 252, 255, 267, 274, 280, 291, 299 Cardiac Output, 234 Cardioselective, 234, 288 Cardiotonic, 17, 234, 278 Cardiotonic Agents, 17, 234 Cardiotoxicity, 127, 163, 234 Cardiovascular disease, 167, 234 Cardiovascular System, 228, 234, 246 Case report, 5, 50, 99, 199, 234, 238 Case series, 234, 238 Case-Control Studies, 31, 234 Catalytic Domain, 17, 235 Catecholamine, 7, 132, 145, 225, 235, 247, 283 Cauda Equina, 56, 235 Caudal, 235, 246, 261, 278, 286 Caudate Nucleus, 229, 235, 278 Causal, 235, 265, 293 Cause of Death, 26, 235 Cell Death, 227, 235, 275 Cell Differentiation, 235, 297 Cell Division, 229, 235, 270, 272, 284, 288 Cell membrane, 83, 89, 231, 233, 235, 245, 252, 255, 284, 297 Cell proliferation, 64, 235, 264, 297 Cell Respiration, 220, 235, 279, 293 Cellulose, 235, 255, 284 Central Nervous System Infections, 235, 258 Central Nervous System Stimulants, 168, 235 Centrifugation, 236, 259, 272, 301 Cerebellar, 45, 236, 292, 304 Cerebellar Diseases, 236, 304 Cerebellum, 175, 236, 254, 286, 292 Cerebral hemispheres, 229, 232, 236 Cerebrovascular, 58, 59, 229, 233, 234, 236, 277 Cerebrum, 236, 284 Cervical, 156, 158, 236, 259, 303 Cervix, 236, 293 Cetirizine, 236, 260 Character, 224, 236, 244
Chemoreceptor, 226, 236 Chemotactic Factors, 236, 240 Chemotherapy, 20, 140, 220, 236 Chest Pain, 187, 236 Child Behavior, 42, 236 Child Psychiatry, 49, 236 Chimeric Proteins, 46, 236 Chloral Hydrate, 17, 236 Chlorpromazine, 146, 237, 254, 304 Cholesterol, 170, 230, 237, 242, 299 Cholestyramine, 169, 198, 237 Cholinergic, 88, 94, 148, 157, 223, 226, 237, 277, 280, 296 Cholinesterase Inhibitors, 237, 280 Chondroitin sulfate, 168, 237 Chorea, 174, 226, 228, 237 Choreatic Disorders, 237 Choroid, 237, 293 Chromaffin Cells, 88, 94, 237, 280 Chromatin, 227, 237, 251, 277 Chromic, 237 Chromosomal, 63, 223, 237 Chromosome, 237, 241, 258 Chronic Disease, 129, 237 Chronic Fatigue Syndrome, 106, 157, 171, 238 Cimetidine, 169, 238 Cinchona, 238, 291 Circadian, 145, 151, 238 Circadian Rhythm, 145, 151, 238 Citalopram, 9, 14, 39, 43, 50, 109, 119, 121, 190, 238 Citric Acid, 134, 238 Citrus, 238 Clamp, 56, 238 Clinical Medicine, 238, 286 Clinical study, 29, 57, 238 Clomipramine, 5, 86, 92, 238 Clonic, 231, 238, 242 Cloning, 35, 46, 63, 231, 238 Clozapine, 146, 238 Coagulation, 231, 239, 259, 302 Coca, 239 Cocaine, 7, 24, 30, 36, 37, 46, 47, 54, 63, 67, 129, 165, 239 Cochlear, 239, 303, 307 Cochlear Diseases, 239, 303 Codeine, 239, 246, 278 Coenzyme, 109, 219, 239 Cofactor, 45, 239, 289, 302 Cognition, 12, 50, 118, 137, 239, 266, 276
Index 315
Cognitive behavior therapy, 19, 58, 167, 239 Cognitive restructuring, 239, 299 Colitis, 239, 265 Collapse, 232, 239 Combination Therapy, 118, 239 Communication Disorders, 123, 177, 196, 239 Comorbidity, 9, 14, 44, 239 Complement, 26, 223, 240, 256, 296 Complementary and alternative medicine, 97, 98, 113, 240 Complementary medicine, 98, 240 Complete remission, 240, 293 Computational Biology, 197, 240 Computed tomography, 98, 240, 241, 294 Computerized axial tomography, 240, 241, 294 Computerized tomography, 240 Conception, 34, 241, 253, 287 Concomitant, 32, 52, 57, 97, 241 Conduction, 38, 241 Confounding, 60, 241 Confusion, 241, 247, 261, 276 Congenita, 241, 291 Congestion, 226, 241 Congestive heart failure, 140, 234, 241 Conjugated, 230, 241, 244, 259 Conjugation, 144, 241, 300 Connective Tissue, 232, 241, 255, 269, 282, 294 Consciousness, 216, 223, 224, 241, 244, 247 Constipation, 6, 148, 170, 172, 198, 226, 241, 255, 265 Constitutional, 241, 274 Consultation, 29, 38, 241 Consumption, 241, 256, 278, 293 Continence, 173, 241 Contractility, 173, 241 Contraindications, ii, 156, 241 Control group, 28, 55, 241, 291 Controlled study, 9, 14, 69, 242 Convulsants, 147, 148, 242 Convulsions, 126, 215, 225, 229, 242, 249, 261, 276 Coordination, 44, 174, 236, 242 Cor, 29, 52, 242 Coronary, 57, 58, 224, 234, 242, 272, 274 Coronary Artery Bypass, 58, 242 Coronary heart disease, 234, 242 Coronary Thrombosis, 242, 272, 274
Cortex, 53, 83, 89, 101, 227, 242, 251, 252, 253, 275, 286, 290, 292 Cortical, 6, 84, 90, 118, 143, 242, 252, 286, 290, 295 Corticosteroid, 52, 242 Courtship, 227, 243 Cranial, 48, 131, 141, 236, 243, 258, 265, 276, 278, 280, 282, 306, 307 Cranial Nerves, 131, 243 Craniocerebral Trauma, 229, 243, 258, 303 Criterion, 43, 243 Cromolyn Sodium, 169, 243 Crowns, 243, 245 Cryostat, 243, 254 Cultured cells, 24, 34, 243 Curare, 243, 274 Curative, 243, 302 Cutaneous, 231, 233, 243 Cyanide, 243, 271 Cyclic Vomiting Syndrome, 205, 243 Cyproheptadine, 146, 243 Cystitis, 168, 179, 204, 243 Cystoscopy, 179, 243 Cytochrome, 21, 144, 238, 243 Cytokine, 62, 71, 244 Cytoplasm, 227, 229, 235, 244, 251, 257, 273, 277, 301 Cytoskeleton, 145, 244 Cytotoxic, 27, 233, 244, 262, 291, 297 D Databases, Bibliographic, 197, 244 Deamination, 244, 273 Decarboxylation, 230, 244, 260 Defecation, 34, 244 Degenerative, 174, 244, 273, 279 Deletion, 227, 244 Delirium, 159, 165, 174, 226, 244 Delusions, 177, 244, 258, 290 Dementia, 78, 156, 158, 159, 165, 176, 177, 180, 226, 244 Denaturation, 245, 285 Dendrites, 118, 245, 276, 290 Density, 60, 61, 236, 245, 278, 298 Dental Abutments, 245 Dental Caries, 5, 245 Dentate Gyrus, 25, 245, 260 Dentures, 177, 245 Depersonalization, 245, 280, 295 Depolarization, 245, 297 Depressive Disorder, 8, 27, 43, 44, 55, 57, 74, 117, 120, 121, 122, 144, 245, 268 Deprivation, 104, 245
316 Antidepressants
Derealization, 245, 280 Dermatitis, 245, 260 Desensitization, 7, 56, 245 Desipramine, 19, 29, 38, 47, 62, 84, 91, 120, 134, 137, 166, 171, 187, 205, 245 Desmopressin, 176, 245 Detergents, 246, 266 Detoxification, 133, 246 Deuterium, 246, 260 Dextroamphetamine, 223, 246 Dextromethorphan, 141, 246 Diabetes Mellitus, 41, 140, 246, 257, 259 Diagnostic procedure, 125, 186, 246 Dialyzer, 246, 259 Diaphragm, 174, 246, 260 Diarrhea, 171, 172, 198, 222, 225, 237, 246, 255, 265 Diarrhoea, 246, 256 Diastolic, 246, 261 Dicyclomine, 199, 246 Diencephalon, 246, 251, 261, 286, 302 Diffusion, 37, 66, 231, 246, 247 Diffusion of Innovation, 37, 246 Digestion, 170, 222, 230, 232, 246, 249, 256, 263, 265, 268, 281, 299 Digestive system, 123, 173, 246, 256, 274 Digestive tract, 228, 247, 297 Dihydrotestosterone, 247, 292 Dilatation, 247, 287, 306 Dilution, 247, 284 Dimethyl, 146, 173, 176, 247 Diploid, 247, 284 Direct, iii, 14, 16, 24, 35, 46, 57, 83, 89, 189, 235, 238, 247, 248, 256, 291, 292, 301 Disease Progression, 27, 247, 307 Disinfectant, 219, 247, 252 Disorientation, 241, 244, 247 Dissociation, 32, 221, 247 Dissociative Disorders, 247 Distal, 140, 229, 242, 247, 256, 282, 285, 287, 289 Disulfiram, 30, 247 Diuresis, 233, 247 Diuretic, 247, 298 Dizziness, 172, 247, 280, 307 Domesticated, 247, 257 Dopa, 247, 267 Dopamine Agonists, 30, 168, 248 Dopamine Antagonists, 168, 248 Dorsal, 62, 143, 248, 251, 286, 296, 298 Dorsum, 248, 255 Dosage Forms, 142, 248
Double-blinded, 62, 248 Drive, ii, vi, 11, 25, 36, 81, 156, 159, 164, 167, 171, 248, 267 Drug Costs, 23, 248 Drug Design, 33, 248 Drug Interactions, 21, 84, 91, 156, 165, 166, 192, 248 Drug Monitoring, 78, 248 Drug Tolerance, 248, 303 Duct, 249, 250, 252, 262, 294 Dumping Syndrome, 243, 249 Duodenum, 230, 249, 255, 280, 299 Dyes, 229, 249, 277, 300 Dyskinesia, 226, 238, 249 Dyspepsia, 167, 169, 205, 249, 263 Dysphonia, 174, 249 Dysphoric, 118, 245, 249 Dyspnea, 249, 280 Dystonia, 174, 226, 249 Dystrophy, 135, 249 E Effector, 32, 131, 219, 240, 249, 276, 283 Effector cell, 249, 276 Ejaculation, 139, 249, 295 Elective, 249 Electroconvulsive Therapy, 152, 249 Electrolyte, 242, 244, 249, 272, 286, 297 Electrons, 229, 249, 265, 279, 291 Electrophysiological, 7, 12, 16, 34, 35, 249 Electroplating, 249, 300 Embryo, 231, 235, 249, 263, 287, 298, 305 Embryo Transfer, 249, 287 Emesis, 148, 216, 226, 250 Emetic, 226, 250 Empiric, 34, 62, 250 Empirical, 9, 14, 66, 99, 120, 250 Emulsion, 229, 250, 254 Enamel, 245, 250 Encephalitis, 174, 250 Encephalitis, Viral, 250 Endocarditis, 233, 250 Endocrine System, 250, 276 Endolymphatic Duct, 250 Endolymphatic Sac, 172, 250 Endometrium, 250, 271 Endopeptidases, 250, 289 Endothelium, 250, 277 Endothelium-derived, 250, 277 Endotoxin, 251, 305 Energetic, 104, 251 Enhancer, 49, 132, 150, 251 Enteric Nervous System, 4, 35, 251
Index 317
Entorhinal Cortex, 251, 260 Enuresis, 175, 176, 251 Environmental Health, 196, 198, 251 Enzymatic, 199, 230, 233, 235, 240, 245, 251, 260, 285 Eosinophils, 251, 257, 267 Ependyma, 227, 251, 302 Epidemic, 26, 251 Epidemiological, 10, 59, 251 Epigastric, 167, 251, 280 Epinephrine, 7, 130, 220, 230, 237, 248, 251, 266, 277, 305 Epithalamus, 246, 251, 268 Erectile, 17, 106, 251, 281 Erection, 170, 251 Ergot, 232, 251 Erythrocyte Indices, 231, 251 Erythrocytes, 229, 231, 232, 252, 296 Erythromycin, 170, 252 Esophagitis, 252, 300 Esophagus, 4, 246, 247, 252, 256, 259, 269, 283, 292, 299 Estrogen, 23, 199, 252, 288 Ethanol, 103, 238, 252 Ether, 83, 90, 252 Ethnic Groups, 38, 252 Eukaryotic Cells, 49, 252, 263, 279 Euphoria, 30, 252 Evacuation, 241, 252, 255, 267 Evoke, 252, 299 Excitability, 34, 130, 252, 275, 291 Excitation, 18, 34, 235, 236, 252 Excitatory, 55, 118, 252, 257, 276 Excitatory Amino Acids, 252, 276 Exhaustion, 106, 224, 243, 252 Exocrine, 252, 280 Exocytosis, 132, 252, 301 Exogenous, 248, 252, 289, 300, 305 Exon, 222, 252 External-beam radiation, 253, 265, 291, 309 Extracellular, 16, 46, 228, 241, 253, 272, 297 Extracellular Space, 253, 272 Extracorporeal, 253, 259 Extraction, 32, 253 Extrapyramidal, 221, 222, 226, 248, 253 Extremity, 253, 295 F Fallopian Tubes, 253, 293 Family Planning, 197, 253 Fat, 173, 227, 232, 242, 253, 268, 285, 294, 297
Fatigue, 28, 157, 238, 253, 259 Fatty acids, 140, 152, 221, 234, 253, 268, 288 Feces, 173, 241, 253, 299 Fentanyl, 170, 253 Fertilization in Vitro, 253, 287 Fertilizers, 253, 300 Fetus, 253, 284, 287, 298, 299, 305, 306 Fibrin, 231, 253, 302 Fissure, 245, 253, 286 Fistula, 172, 253 Fixation, 253, 296 Flatus, 254, 255 Fludrocortisone, 175, 254 Fluorescence, 21, 33, 254 Fluoxetine, 25, 38, 41, 43, 45, 46, 54, 60, 69, 75, 96, 120, 121, 190, 254 Fluphenazine, 146, 254 Flushing, 247, 254 Fluvoxamine, 21, 109, 121, 190, 254 Forearm, 231, 254 Formularies, 23, 254, 283 Formulary, 23, 254 Forskolin, 84, 85, 90, 92, 254 Fossa, 236, 254 Fourth Ventricle, 254, 269, 302 Fractionation, 254, 301 Frontal Lobe, 59, 254, 286 Frozen Sections, 158, 254 Functional Disorders, 3, 171, 255 Fungi, 225, 228, 241, 255, 272, 309 Fungistatic, 230, 255 Fungus, 233, 251, 255 G Gait, 22, 158, 236, 255 Gallbladder, 219, 230, 246, 255, 256 Ganglia, 130, 166, 219, 229, 251, 255, 275, 280, 282, 300 Ganglion, 255, 278, 307 Gap Junctions, 255, 301 Gas, 173, 223, 234, 246, 254, 255, 260, 263, 265, 277, 306 Gastrectomy, 243, 255 Gastric, 29, 85, 91, 216, 238, 248, 255, 256, 259, 260, 281, 292 Gastric Acid, 85, 91, 238, 255 Gastric Emptying, 255, 256 Gastric Juices, 255, 281 Gastric Mucosa, 255, 281 Gastrin, 238, 255, 260 Gastritis, 167, 256, 300 Gastroenteritis, 198, 256
318 Antidepressants
Gastroenterology, 4, 167, 169, 171, 198, 256 Gastroesophageal Reflux, 106, 167, 256 Gastrointestinal tract, 171, 237, 238, 252, 256, 267, 281, 296 Gastroparesis, 170, 256 Gene Expression, 17, 24, 40, 67, 103, 143, 256 General practitioner, 79, 256 Genetic Engineering, 231, 238, 256 Genetic testing, 256, 285 Genetics, 25, 34, 241, 256 Genital, 228, 256, 306 Genotype, 256, 283 Geriatric, 16, 82, 83, 88, 89, 101, 103, 157, 158, 176, 256 Germ Cells, 256, 270, 278, 298 Giardiasis, 256, 271 Gland, 45, 130, 156, 220, 256, 261, 269, 280, 284, 288, 295, 299, 302 Glottis, 174, 256, 260 Glucocorticoid, 16, 27, 52, 70, 256, 272 Glucose, 42, 101, 141, 235, 246, 257, 259, 261, 264, 294, 298 Glucose Intolerance, 246, 257 Glutamate, 48, 75, 246, 257, 271 Glycine, 230, 257, 296 Glycoprotein, 73, 257, 302, 305 Glycosaminoglycan, 237, 257 Glycosidic, 234, 257 Glycosuria, 141, 257 Gonadal, 257, 299 Gout, 175, 257 Governing Board, 257, 286 Graft, 58, 257, 262 Grafting, 242, 257, 263 Granule, 45, 245, 257 Granulocytes, 257, 267, 297, 308 Gravis, 53, 257 Guanylate Cyclase, 257, 277 Guinea Pigs, 84, 91, 257 Gyrus Cinguli, 257, 268 H Haematemesis, 250, 258 Hair Cells, 258, 307 Half-Life, 142, 258 Hallucination, 177, 258 Hallucinogens, 258, 290 Haloperidol, 69, 109, 146, 258 Haploid, 258, 284 Haptens, 221, 258
Headache, 67, 68, 102, 118, 233, 258, 261, 287, 306 Headache Disorders, 258 Health Behavior, 10, 258 Health Policy, 22, 258 Health Services, 44, 164, 258 Health Status, 15, 55, 258 Hearing aid, 177, 258 Hearing Disorders, 239, 258 Heart attack, 234, 258 Heart failure, 259 Heartbeat, 216, 259 Heartburn, 106, 167, 172, 259, 263 Hematocrit, 231, 251, 259 Heme, 244, 259 Hemiplegia, 228, 259 Hemodialysis, 102, 246, 259 Hemoglobin, 231, 251, 252, 259 Hemoperfusion, 102, 259 Hemorrhage, 243, 258, 259, 299 Hemostasis, 259, 296 Hepatic, 221, 244, 259, 273 Hereditary, 140, 174, 237, 257, 259, 273, 282 Heredity, 256, 259 Heterogeneity, 57, 143, 221, 259 Hiccup, 168, 237, 248, 260 Hippocampus, 16, 23, 25, 45, 52, 53, 63, 71, 86, 87, 93, 143, 185, 245, 260, 268, 290, 296, 300 Histamine, 26, 223, 226, 230, 236, 238, 243, 260, 272, 292 Histidine, 260 Histology, 158, 260 Hoarseness, 177, 260 Homeostasis, 20, 53, 55, 260, 280, 298 Homologous, 7, 260, 296, 301 Hormonal, 23, 32, 131, 228, 237, 243, 260 Hormone Replacement Therapy, 60, 260 Hormone therapy, 220, 260 Hybrid, 260 Hybridization, 143, 260 Hydroalcoholic, 102, 260 Hydrogen, 126, 149, 219, 223, 229, 234, 245, 246, 260, 273, 277, 278, 279, 282, 289 Hydrolysis, 17, 150, 260, 283, 285, 289 Hydrophobic, 56, 246, 260 Hydroxylation, 84, 91, 260 Hydroxyzine, 169, 260 Hyperalgesia, 135, 261 Hyperglycaemia, 141, 261 Hyperglycemia, 42, 261
Index 319
Hypericum, 84, 90, 98, 99, 100, 101, 102, 103, 110, 112, 162, 261 Hypersecretion, 167, 261 Hypersensitivity, 199, 222, 245, 261, 267, 294, 296 Hypertension, 38, 233, 234, 261, 265, 266, 288 Hyperthyroidism, 261, 288 Hypertrophy, 242, 261, 304 Hyperuricemia, 257, 261 Hypnotherapy, 167, 261 Hypnotic, 229, 236, 261 Hypoglycaemia, 244, 261 Hypoglycemia, 156, 261 Hypotension, 5, 226, 242, 247, 261, 278 Hypothalamic, 29, 48, 52, 57, 131, 143, 261 Hypothalamus, 52, 131, 227, 228, 246, 261, 268, 284, 296, 302 Hypothermia, 70, 261 Hypothyroidism, 57, 261 Hypoxanthine, 261, 308 Hypoxia, 244, 261 I Iatrogenic, 118, 261 Id, 95, 104, 205, 212, 214, 262 Idiopathic, 174, 262 Illusion, 262, 307 Imidazole, 260, 262, 292 Imipramine, 36, 46, 54, 55, 129, 137, 143, 161, 166, 187, 238, 262, 305 Immune adjuvant, 170, 262 Immune function, 19, 262 Immune response, 19, 220, 225, 243, 258, 262, 296, 300, 307 Immune system, 20, 152, 249, 262, 267, 269, 306, 308 Immunity, 27, 71, 141, 262 Immunization, 262, 296 Immunoblotting, 46, 262 Immunodeficiency, 82, 88, 103, 262 Immunologic, 152, 236, 262, 291 Immunology, 220, 221, 262 Immunophilin, 233, 262 Immunosuppressive, 97, 158, 233, 257, 262 Immunosuppressive Agents, 158, 262 Immunotherapy, 245, 262 Impaction, 174, 262 Impairment, 9, 10, 11, 14, 22, 46, 66, 117, 156, 221, 244, 249, 263, 266, 271, 290 Implant radiation, 263, 264, 265, 291, 309 Implantation, 241, 263 Impotence, 107, 170, 251, 263
In situ, 17, 23, 45, 52, 263 In Situ Hybridization, 17, 23, 52, 263 In vitro, 13, 18, 20, 21, 35, 45, 56, 58, 62, 79, 84, 91, 130, 249, 263, 285 In vivo, 12, 13, 16, 18, 19, 21, 24, 32, 34, 36, 56, 58, 84, 91, 263, 272 Incision, 263, 265, 303 Incompetence, 256, 263 Incontinence, 166, 173, 176, 198, 199, 246, 263, 288, 295 Indicative, 159, 263, 281, 306 Indigestion, 167, 263 Induction, 21, 29, 224, 226, 263, 288 Infant Behavior, 236, 263 Infant Care, 51, 263 Infarction, 263 Infertility, 232, 263, 306 Inflammatory bowel disease, 152, 165, 169, 263 Infusion, 19, 23, 264 Ingestion, 264, 271, 285 Inhalation, 260, 264, 285 Initiation, 59, 264, 304 Inlay, 264, 293 Innervation, 264, 282, 295, 303 Inorganic, 127, 128, 150, 264, 274 Inositol, 264, 271, 295 Inotropic, 248, 264 Inpatients, 82, 88, 264 Insecticides, 264, 308 Insight, 16, 17, 20, 23, 47, 264 Insomnia, 28, 107, 133, 145, 151, 177, 236, 264, 287 Insulin, 41, 141, 146, 156, 170, 264, 266, 305 Insulin-dependent diabetes mellitus, 264 Interindividual, 38, 264 Interleukins, 262, 264 Intermittent, 175, 264, 269 Internal Medicine, 256, 264, 275 Internal radiation, 264, 265, 291, 309 Interpersonal Relations, 144, 264 Interstitial, 168, 179, 204, 232, 253, 264, 265, 293, 309 Intervention Studies, 28, 49, 265 Intestinal, 5, 35, 205, 265 Intestine, 152, 232, 265, 267 Intoxication, 102, 244, 265, 308 Intracellular, 24, 55, 73, 233, 263, 265, 271, 277, 286, 288, 292, 295, 296 Intracranial Hypertension, 258, 265, 303 Intraindividual, 16, 265 Intraocular, 254, 265
320 Antidepressants
Intraocular pressure, 254, 265 Intrathecal, 13, 265 Intravenous, 264, 265 Intrinsic, 35, 221, 265 Invasive, 60, 168, 262, 265, 270 Invertebrates, 130, 265, 278 Involuntary, 174, 176, 229, 237, 251, 265, 274, 298 Ion Channels, 12, 228, 265, 276, 301 Ions, 229, 233, 237, 247, 249, 260, 265, 273, 297 Irradiation, 20, 265, 309 Irritable Bowel Syndrome, 4, 6, 68, 107, 169, 171, 172, 176, 187, 198, 205, 255, 265 Ischemia, 224, 228, 265, 276 Isethionic Acid, 128, 266 Islet, 141, 266 Isoproterenol, 13, 45, 266 Isozymes, 39, 266 Itraconazole, 21, 266 J Joint, 68, 108, 157, 175, 199, 228, 266, 279 K Kb, 196, 266 Keratolytic, 245, 266 Ketanserin, 7, 266 Keto, 127, 266 Ketoconazole, 84, 91, 266 Kidney Disease, 123, 170, 196, 205, 266 Kinetic, 7, 21, 266 L Labile, 240, 266 Labyrinth, 250, 266, 279, 282, 307 Lactation, 34, 266, 288 Lag, 176, 266 Language Development, 266, 267 Language Development Disorders, 266, 267 Language Disorders, 239, 266 Language Therapy, 177, 266 Large Intestine, 246, 247, 265, 267, 292, 297 Larynx, 256, 267, 303, 306, 308 Latent, 267, 286 Lavage, 216, 267 Laxative, 221, 267, 298 Least-Squares Analysis, 267, 292 Lesion, 55, 59, 231, 242, 267, 268, 301, 305 Lethargy, 205, 261, 267 Leucocyte, 222, 267 Leukocytes, 20, 229, 231, 232, 236, 251, 257, 264, 267, 273, 277, 282, 305 Leukotrienes, 227, 267, 268
Levodopa, 175, 247, 267, 295 Levorphanol, 246, 267 Libido, 145, 151, 224, 267 Library Services, 212, 267 Lidocaine, 62, 168, 267 Ligaments, 242, 267 Ligands, 21, 268 Likelihood Functions, 268, 292 Limbic, 52, 53, 223, 258, 268, 286 Limbic System, 53, 223, 258, 268, 286 Linear Models, 268, 292 Lip, 156, 268 Lipid, 130, 264, 266, 268 Lipophilic, 144, 268 Lipoxygenase, 170, 227, 267, 268 Lipoxygenase Inhibitors, 170, 268 Lithium, 73, 83, 84, 85, 86, 87, 89, 90, 92, 93, 110, 146, 152, 160, 181, 190, 226, 268 Lithium Carbonate, 152, 268 Liver, 144, 155, 219, 221, 227, 230, 238, 246, 250, 253, 255, 256, 259, 268, 273, 280, 294 Liver scan, 268, 294 Localization, 7, 33, 45, 63, 268 Localized, 7, 32, 138, 144, 151, 175, 245, 254, 259, 263, 268, 273, 284, 305, 306 Locomotion, 268, 269, 284 Locomotor, 87, 93, 269 Locus Coeruleus, 63, 64, 83, 89, 143, 269 Logistic Models, 269, 292 Longitudinal Studies, 29, 269 Longitudinal study, 38, 59, 269 Long-Term Care, 173, 269 Loop, 172, 269 Lower Esophageal Sphincter, 256, 269 Lumbar, 140, 229, 235, 269, 295, 302 Lymph, 156, 158, 236, 250, 269 Lymph node, 156, 158, 236, 269 Lymphatic, 250, 263, 269, 285 Lymphatic system, 269 Lymphoid, 225, 267, 269 M Macrolides, 21, 269 Macrophage, 79, 269 Magnetic Resonance Imaging, 270, 294 Malignant, 135, 157, 226, 270, 291 Malnutrition, 221, 228, 270 Mammary, 60, 242, 270 Mania, 29, 70, 77, 270 Manic, 100, 226, 231, 268, 270, 290 Manic-depressive psychosis, 270, 290 Maternal Deprivation, 52, 270 Meatus, 270, 306
Index 321
Mediate, 23, 24, 27, 30, 32, 115, 248, 270, 292, 307 Mediator, 247, 270, 296 Medical Records, 270, 293 Medical Staff, 248, 270 Medicament, 83, 89, 141, 270 MEDLINE, 197, 270 Medullary, 246, 270 Medulloblastoma, 7, 270 Meiosis, 270, 301 Melanin, 269, 270, 283, 305 Membrane, 61, 129, 132, 145, 228, 235, 237, 240, 245, 246, 251, 252, 259, 265, 267, 270, 272, 274, 279, 284, 291, 293, 294, 297, 301, 308 Membrane Glycoproteins, 270 Memory, 16, 35, 47, 53, 177, 224, 244, 270 Meninges, 235, 243, 270, 271 Meningitis, 266, 271 Menopause, 271, 282, 286, 288 Menstrual Cycle, 51, 118, 271, 287 Menstruation, 222, 271, 287 Mental Disorders, 123, 165, 220, 236, 266, 271, 289, 290 Mental Health, iv, 6, 10, 21, 22, 33, 43, 44, 54, 66, 83, 84, 89, 90, 117, 118, 119, 120, 121, 123, 157, 196, 200, 204, 271, 290 Mental Health Services, iv, 6, 21, 44, 200, 271 Mental Processes, 247, 271, 289 Mental Retardation, 37, 239, 271 Mentors, 11, 44, 271 Mesencephalic, 269, 271, 292 Mesolimbic, 87, 93, 226, 271, 307 Meta-Analysis, 64, 72, 100, 101, 271 Metabolic disorder, 141, 205, 257, 271 Metabolite, 30, 69, 84, 90, 137, 238, 247, 260, 271, 277, 287 Metabotropic, 75, 271 Methanol, 32, 100, 271 Methionine, 82, 88, 134, 247, 271, 300 Methylene Blue, 169, 271 Metoclopramide, 170, 271 Metronidazole, 169, 271 MI, 21, 130, 172, 217, 272 Mianserin, 134, 272 Microbe, 272, 303 Microbiology, 220, 228, 272 Microdialysis, 11, 272 Microorganism, 239, 272, 308 Micro-organism, 245, 272 Microscopy, 33, 272
Microscopy, Fluorescence, 33, 272 Microsomal, 144, 272 Mineralocorticoid, 52, 254, 272 Mitosis, 227, 272 Mobilization, 130, 140, 272 Modeling, 16, 41, 248, 272 Modification, 19, 48, 55, 174, 176, 187, 256, 272, 290 Molecular Structure, 273, 304 Monitor, 54, 273, 277 Monoamine Oxidase, 4, 5, 11, 73, 97, 137, 140, 141, 145, 152, 165, 190, 223, 225, 246, 273, 295, 305 Monoclonal, 262, 265, 273, 291, 309 Monoclonal antibodies, 262, 273 Monocytes, 79, 267, 273 Mononuclear, 73, 273, 305 Monophosphate, 17, 273 Mood Disorders, 23, 40, 49, 53, 77, 82, 89, 103, 165, 273 Morphine, 13, 86, 226, 239, 273, 275, 278 Motility, 35, 167, 255, 273, 296 Motion Sickness, 273, 275, 295 Motor Activity, 242, 273 Motor nerve, 56, 273, 274 Movement Disorders, 174, 222, 226, 273 Mucins, 273, 294 Mucosa, 255, 274, 288, 300 Mucositis, 86, 92, 274 Mucus, 166, 171, 173, 274, 305 Muscle relaxant, 135, 147, 148, 157, 168, 169, 175, 224, 274 Muscle Relaxation, 167, 274 Muscle tension, 130, 274 Muscular Dystrophies, 249, 274 Mutagenesis, 21, 46, 274 Mutagens, 274 Myasthenia, 53, 274 Mydriatic, 274, 295 Myelin, 49, 274 Myocardial infarction, 71, 226, 242, 272, 274, 288 Myocardium, 224, 272, 274 Myoclonus, 174, 274 Myosin, 233, 274 Myotonia, 274, 291 N Naloxone, 133, 274 Naltrexone, 133, 274 Narcosis, 275 Narcotic, 168, 169, 170, 199, 219, 253, 267, 273, 274, 275
322 Antidepressants
Nausea, 148, 170, 205, 225, 226, 243, 247, 248, 256, 263, 275, 277, 280, 287 NCI, 1, 122, 195, 275 Neck Muscles, 175, 275 Necrosis, 227, 263, 272, 274, 275, 296 Nelfinavir, 21, 275 Neocortex, 53, 275 Neonatal, 34, 275 Nephrology, 175, 176, 275 Nephropathy, 266, 275 Nerve, 54, 56, 82, 88, 130, 131, 135, 139, 140, 141, 151, 166, 174, 180, 220, 223, 224, 229, 235, 245, 251, 255, 256, 264, 269, 270, 273, 275, 276, 277, 278, 282, 284, 285, 286, 287, 293, 294, 295, 298, 299, 301, 302, 304, 306, 307 Nerve Endings, 82, 88, 275, 301 Nerve Fibers, 131, 275, 302, 307 Nerve Growth Factor, 275, 277 Networks, 53, 275 Neural, 26, 48, 53, 82, 83, 84, 85, 86, 89, 90, 92, 162, 165, 221, 245, 273, 276, 296, 297 Neuralgia, 276, 286 Neuroeffector Junction, 275, 276 Neuroendocrine, 20, 157, 276 Neuroendocrinology, 83, 89, 157, 276 Neuroleptic, 157, 160, 177, 221, 226, 238, 276 Neurologic, 18, 224, 276 Neuromuscular, 53, 219, 276, 288, 293 Neuromuscular Junction, 53, 219, 276, 293 Neuronal, 12, 17, 24, 45, 55, 56, 126, 129, 130, 143, 148, 238, 275, 276, 282 Neuropathy, 141, 170, 223, 229, 276, 282 Neuropeptide, 83, 89, 276 Neuropharmacology, 24, 98, 276 Neuroprotective Agents, 126, 276 Neurosis, 276, 283 Neurotoxic, 69, 276 Neurotoxicity, 46, 132, 246, 276 Neurotransmitters, 7, 12, 17, 126, 223, 252, 273, 276, 287, 298 Neurotrophins, 53, 277 Neutrons, 222, 265, 277, 291 Neutrophils, 39, 71, 227, 257, 267, 277 Nicotine, 133, 147, 148, 277 Nifedipine, 169, 277 Nimodipine, 82, 88, 277 Nitric Oxide, 45, 55, 85, 92, 277 Nitrogen, 59, 128, 129, 146, 221, 222, 223, 224, 254, 277, 305 Nonulcer Dyspepsia, 167, 277
Nonverbal Communication, 177, 239, 277, 290 Normetanephrine, 137, 277 Nortriptyline, 9, 43, 59, 73, 119, 205, 277 Nuclear, 229, 241, 249, 252, 255, 268, 275, 277, 302 Nuclei, 143, 222, 223, 241, 249, 251, 256, 270, 272, 277, 279, 280, 285, 289, 296, 307 Nucleic acid, 260, 261, 263, 274, 277, 278, 290 Nucleic Acid Hybridization, 260, 278 Nucleus Accumbens, 48, 278, 307 Nutritional Status, 25, 278 O Octopamine, 129, 130, 278 Oculi, 231, 278 Odour, 227, 278 Office Management, 176, 278 Office Visits, 54, 278 Ointments, 248, 278 Oocytes, 84, 91, 278 Opacity, 245, 278 Operon, 24, 278, 293 Opium, 273, 278 Optic Chiasm, 261, 278 Optic Nerve, 278, 293 Oral Health, 5, 164, 279 Oral Hygiene, 158, 279 Orbicularis, 231, 279 Organelles, 236, 244, 273, 279 Orgasm, 249, 279 Orofacial, 158, 279 Orthostatic, 5, 37, 226, 279 Osmosis, 279 Osmotic, 138, 221, 279 Ossicles, 279 Osteoarthritis, 107, 157, 199, 279 Osteoporosis, 31, 279 Otosclerosis, 172, 279 Outpatient, 27, 38, 120, 279 Ovaries, 253, 279, 293 Overdose, 9, 69, 76, 215, 242, 279 Oxidation, 31, 144, 219, 227, 244, 279 Oxidative metabolism, 21, 220, 267, 279 P Pacemaker, 166, 280 Palliative, 280, 302 Palsies, 141, 280 Palsy, 174, 280, 298 Pancreas, 141, 219, 246, 256, 264, 266, 280 Pancreatic, 167, 256, 280 Pancreatic Juice, 256, 280
Index 323
Panic, 34, 105, 138, 145, 254, 262, 280 Panic Disorder, 34, 145, 254, 262, 280 Paraganglia, Chromaffin, 237, 280 Paralysis, 227, 243, 271, 280, 298 Parasympathetic Nervous System, 131, 280 Parasympathomimetics, 168, 280 Paresthesias, 280 Parkinsonism, 226, 227, 267, 280 Paroxetine, 30, 36, 46, 50, 60, 96, 121, 149, 150, 191, 281 Paroxysmal, 135, 224, 258, 281, 306 Partial remission, 281, 293 Partial response, 117, 281 Particle, 134, 281, 298, 304 Patch, 133, 281, 304 Pathogenesis, 36, 176, 281 Pathologic, 165, 169, 219, 227, 231, 233, 242, 261, 281, 289, 306 Pathologic Processes, 227, 281 Pathophysiology, 4, 37, 40, 57, 158, 165, 167, 168, 173, 281 Patient Advocacy, 177, 281 Patient Education, 169, 176, 180, 187, 204, 210, 212, 217, 281 Patient Selection, 205, 281 Pelvic, 174, 281, 288 Penis, 249, 281, 293 Pentosan polysulfate, 168, 281 Pepsin, 238, 281 Pepsin A, 238, 281 Peptic, 167, 230, 281, 300 Peptic Ulcer, 167, 230, 281 Peptide, 48, 63, 250, 281, 285, 289, 302 Perception, 148, 167, 245, 258, 282, 295 Perennial, 261, 282 Pergolide, 175, 282 Perilymph, 172, 282 Perimenopausal, 184, 282 Perineal, 166, 282 Perineum, 282 Periodontal disease, 5, 282 Perioral, 158, 282 Peripheral blood, 73, 222, 282 Peripheral Nerves, 135, 140, 151, 282, 285, 298 Peripheral Nervous System, 131, 259, 280, 282, 287, 300 Peripheral Neuropathy, 141, 282 Peroneal Nerve, 282, 295 Peroxidase, 57, 227, 282 Peroxide, 282
PH, 66, 72, 98, 282 Pharmaceutical Preparations, 134, 235, 252, 282 Pharmaceutical Solutions, 248, 282 Pharmacist, 134, 283 Pharmacodynamic, 16, 180, 283 Pharmacokinetic, 16, 86, 92, 180, 283 Pharmacologic, 7, 33, 38, 40, 44, 46, 57, 120, 139, 151, 159, 168, 176, 224, 258, 283, 303 Pharmacopoeias, 254, 283 Pharmacotherapy, 19, 20, 40, 41, 50, 101, 135, 171, 199, 283 Pharynx, 256, 283, 306 Phenazopyridine, 169, 199, 283 Phenotype, 34, 48, 283 Phenyl, 56, 126, 136, 169, 283 Phenylalanine, 111, 141, 281, 283, 305 Phobia, 145, 184, 283 Phobic Disorders, 283 Phosphodiesterase, 12, 17, 283, 294 Phospholipases, 283, 297 Phospholipids, 253, 264, 283 Phosphorus, 233, 284 Phosphorylated, 23, 35, 239, 284 Phototransduction, 284, 295 Physical Examination, 169, 171, 175, 199, 284 Physiologic, 24, 167, 221, 231, 247, 258, 271, 274, 284, 288, 292, 296, 304 Physiology, 5, 32, 99, 100, 130, 176, 249, 256, 275, 284 Pilot study, 28, 49, 54, 104, 284 Pineal Body, 251, 284 Pineal gland, 45, 284 Pituitary Gland, 242, 254, 284 Placebo Effect, 167, 284 Placenta, 284, 287, 305 Plants, 146, 222, 228, 230, 234, 238, 239, 257, 261, 277, 284, 285, 294, 303 Plaque, 57, 284 Plasma, 20, 38, 86, 92, 142, 145, 221, 225, 235, 257, 259, 272, 284, 295, 307 Plasma cells, 225, 284 Plasma Volume, 38, 272, 284 Plasticity, 35, 53, 284 Platelet Activation, 285, 297 Platelet Aggregation, 222, 223, 254, 266, 277, 285 Platelets, 39, 121, 227, 277, 278, 285, 302 Platinum, 269, 285 Pleomorphic, 278, 285
324 Antidepressants
Plexus, 285, 295 Point Mutation, 56, 285 Poisoning, 69, 78, 226, 244, 251, 256, 265, 271, 275, 285 Polymerase, 45, 285, 293 Polymerase Chain Reaction, 45, 285 Polymorphic, 245, 285 Polyneuropathies, 140, 285 Polypeptide, 223, 260, 281, 285, 288, 309 Polyunsaturated fat, 46, 285 Polyuria, 141, 285 Pons, 232, 254, 286 Posterior, 130, 223, 229, 236, 237, 248, 251, 275, 279, 280, 284, 286 Postherpetic Neuralgia, 75, 135, 222, 286 Postmenopausal, 279, 286 Postoperative, 72, 286 Postsynaptic, 276, 286, 297, 301 Post-synaptic, 36, 53, 286, 301 Post-traumatic, 145, 258, 273, 286 Post-traumatic stress disorder, 145, 286 Postural, 37, 286 Potassium, 56, 173, 176, 272, 286, 291 Potentiate, 12, 280, 286 Potentiating, 223, 286 Potentiation, 237, 286, 297 Practicability, 286, 304 Practice Guidelines, 200, 286 Preclinical, 52, 55, 117, 151, 286 Precursor, 141, 227, 247, 248, 249, 251, 267, 277, 283, 286, 287, 305 Predisposition, 31, 286 Prefrontal Cortex, 18, 52, 286 Pregnancy Outcome, 16, 287 Premedication, 287, 295 Premenstrual, 51, 107, 118, 131, 171, 287 Premenstrual Syndrome, 51, 107, 118, 131, 171, 287 Prenatal, 52, 249, 287 Prescription Fees, 248, 287 Presynaptic, 7, 137, 275, 276, 287, 301 Presynaptic Terminals, 7, 275, 287, 301 Prevalence, 5, 8, 14, 18, 26, 145, 158, 165, 169, 287 Preventive Health Services, 51, 287 Primary tumor, 143, 287 Primitive neuroectodermal tumors, 270, 287 Probe, 11, 56, 272, 287 Problem Solving, 64, 287 Procaine, 267, 287 Prodrug, 139, 287
Progeny, 241, 287 Progesterone, 287, 288, 299 Progression, 20, 27, 224, 287, 295 Progressive, 5, 167, 174, 235, 244, 248, 257, 274, 275, 279, 285, 287, 293 Projection, 277, 278, 286, 288, 290, 292, 307 Prolactin, 232, 288 Propantheline, 199, 288 Prophase, 278, 288, 301 Prophylaxis, 287, 288, 293 Propranolol, 175, 288 Prospective study, 269, 288 Prostaglandin, 173, 288 Prostaglandins A, 288 Prostate, 107, 288, 293 Protease, 21, 239, 275, 289, 294 Protease Inhibitors, 21, 289 Protective Agents, 233, 289 Protein Binding, 34, 84, 90, 289 Protein C, 140, 221, 223, 229, 289 Protein Isoforms, 222, 289 Protein S, 32, 46, 163, 231, 252, 289, 302 Proteolytic, 222, 240, 289 Protocol, 39, 49, 180, 289 Protons, 222, 260, 289, 291 Protozoa, 241, 272, 289 Proximal, 247, 285, 287, 289, 296 Pruritus, 226, 260, 289 Psoriasis, 289, 293 Psychic, 267, 276, 289, 290, 295 Psychology, 19, 58, 247, 289 Psychomotor, 75, 137, 164, 177, 233, 244, 276, 290 Psychopathology, 157, 290 Psychosis, 29, 34, 158, 226, 290 Psychotherapy, 4, 19, 65, 72, 167, 169, 176, 187, 239, 290, 292 Psychotomimetic, 223, 246, 290 Psychotropic, 4, 22, 126, 127, 128, 132, 134, 152, 157, 162, 180, 290 Psychotropic Drugs, 22, 152, 180, 290 Public Health, 9, 14, 29, 30, 37, 39, 49, 60, 200, 290 Public Policy, 197, 290 Publishing, 4, 5, 38, 62, 159, 172, 176, 198, 290 Pulmonary, 99, 106, 231, 241, 242, 267, 290, 307 Pulmonary Artery, 231, 290, 307 Pulmonary hypertension, 242, 290 Pulse, 216, 273, 290 Purines, 290, 296, 308
Index 325
Pyramidal Cells, 245, 290 Q Quality of Life, 4, 9, 10, 11, 14, 19, 20, 24, 28, 41, 50, 58, 117, 119, 157, 158, 180, 187, 290 Quaternary, 291, 295 Quinidine, 84, 91, 238, 291 Quinine, 83, 89, 144, 172, 238, 291 R Race, 10, 47, 247, 291 Radiation, 86, 92, 220, 224, 229, 253, 254, 264, 265, 271, 281, 291, 294, 309 Radiation therapy, 220, 253, 254, 264, 265, 281, 291, 309 Radioactive, 129, 229, 232, 258, 260, 263, 264, 265, 268, 273, 277, 291, 294, 309 Radiolabeled, 232, 265, 291, 309 Radiotherapy, 232, 265, 291, 309 Random Allocation, 291 Randomization, 9, 22, 58, 118, 291 Randomized clinical trial, 4, 55, 82, 88, 291 Ranitidine, 84, 91, 292 Rape, 286, 292 Reality Testing, 290, 292 Reassurance, 167, 292 Receptors, Serotonin, 292, 296 Recombinant, 46, 292, 306 Recombination, 241, 292 Rectum, 224, 226, 232, 244, 246, 247, 254, 255, 263, 264, 267, 288, 292 Recurrence, 42, 57, 59, 231, 238, 270, 292 Red Nucleus, 292, 307 Reductase, 144, 292 Refer, 1, 37, 158, 232, 240, 247, 254, 255, 268, 276, 277, 290, 292, 307 Reflux, 256, 292, 300 Refraction, 292, 298 Refractory, 13, 19, 82, 88, 292 Regimen, 54, 180, 185, 249, 283, 284, 292 Regression Analysis, 28, 48, 292 Regurgitation, 256, 259, 292 Relapse, 11, 34, 41, 51, 59, 76, 133, 185, 293 Relaxant, 254, 293 Remission, 22, 41, 44, 46, 58, 59, 71, 118, 231, 270, 292, 293 Renal failure, 244, 293 Repressor, 278, 293 Reproduction Techniques, 287, 293 Reproductive system, 25, 293 Research Design, 29, 293 Research Personnel, 37, 293 Respiration, 234, 236, 242, 243, 273, 293
Respiratory Paralysis, 219, 293 Response rate, 184, 293 Restless legs, 86, 93, 293 Restoration, 199, 243, 293 Retina, 45, 237, 278, 284, 293, 294, 308 Retinoids, 158, 293, 308 Retrospective, 5, 62, 64, 293 Retrospective Studies, 62, 293 Retrospective study, 5, 293 Rheumatism, 294 Rheumatoid, 157, 175, 294 Rheumatoid arthritis, 157, 175, 294 Rhinitis, 236, 288, 294 Riboflavin, 95, 96, 294 Ribose, 220, 294 Rigidity, 175, 216, 280, 284, 294 Risk factor, 31, 59, 60, 63, 269, 288, 294 Risperidone, 9, 14, 74, 146, 294 Ritonavir, 21, 294 Rod, 229, 238, 294 Rolipram, 17, 294 S Salicylate, 169, 294 Saliva, 5, 294 Salivary, 5, 130, 156, 246, 294, 308 Salivary glands, 5, 246, 294 Salivation, 5, 294 Saphenous, 242, 294 Saphenous Vein, 242, 294 Saponins, 294, 299 Scans, 59, 294 Schizoid, 295, 308 Schizophrenia, 8, 14, 68, 118, 119, 165, 226, 249, 294, 295, 307, 308 Schizotypal Personality Disorder, 245, 295, 308 Sciatic Nerve, 56, 282, 295, 302 Scopolamine, 170, 172, 230, 295 Screening, 18, 20, 28, 33, 47, 55, 145, 238, 295 Second Messenger Systems, 23, 276, 295 Secretory, 237, 276, 295, 301 Secretory Vesicles, 237, 295 Sedative, 54, 129, 223, 229, 236, 239, 260, 262, 295, 305 Seizures, 18, 234, 244, 281, 295 Selegiline, 111, 175, 295 Self Care, 168, 219, 295 Semen, 249, 288, 295 Semisynthetic, 232, 295 Senile, 174, 226, 279, 296 Sensibility, 223, 261, 296
326 Antidepressants
Sensitization, 18, 148, 150, 296 Septal, 268, 296 Septal Nuclei, 268, 296 Sequencing, 6, 285, 296 Sequester, 296, 301 Serine, 137, 250, 296 Serotonin Agonists, 296 Serotonin Antagonists, 168, 296 Sertraline, 9, 15, 19, 41, 51, 54, 57, 59, 61, 112, 119, 121, 140, 144, 191, 296 Serum, 34, 50, 61, 66, 77, 87, 221, 223, 240, 272, 296, 305 Shock, 71, 217, 234, 274, 296, 304 Signal Transduction, 16, 20, 24, 33, 46, 233, 264, 296 Signs and Symptoms, 133, 165, 173, 293, 297 Skeletal, 56, 147, 148, 224, 237, 238, 243, 266, 274, 291, 297, 298 Skeleton, 266, 288, 297 Skull, 243, 297, 301 Sleep Deprivation, 101, 297 Small intestine, 152, 171, 230, 249, 256, 260, 265, 297 Smooth muscle, 17, 166, 173, 174, 222, 223, 232, 233, 254, 260, 273, 297, 298, 300 Social Environment, 290, 297 Social Support, 44, 51, 297, 299 Social Work, 45, 297 Sodium, 56, 83, 90, 146, 168, 170, 179, 257, 272, 284, 291, 297 Sodium Channels, 56, 284, 291, 297 Soft tissue, 158, 175, 232, 297 Solitary Nucleus, 228, 297 Solvent, 219, 230, 252, 271, 279, 282, 298 Soma, 290, 298 Somatic, 35, 67, 133, 243, 268, 270, 272, 282, 286, 298, 306 Sorbitol, 173, 298 Sound wave, 241, 298 Soybean Oil, 285, 298 Spasm, 175, 226, 228, 231, 260, 271, 298 Spasmodic, 174, 175, 298 Spastic, 265, 298 Specialist, 158, 206, 298 Specificity, 17, 33, 35, 48, 129, 221, 227, 250, 298 Spectrum, 21, 67, 148, 162, 266, 298 Sphincter, 199, 267, 298 Spinal Nerves, 131, 282, 298 Spontaneous Abortion, 287, 298 Stabilization, 9, 14, 49, 299
Staging, 294, 299 Steel, 238, 299 Steroid, 34, 104, 146, 294, 299 Stillbirth, 287, 299 Stimulant, 8, 11, 57, 70, 132, 223, 233, 243, 246, 260, 266, 299 Stimulus, 13, 148, 174, 241, 248, 249, 252, 258, 264, 265, 266, 280, 283, 299, 302 Stomach, 148, 170, 219, 246, 247, 252, 255, 256, 260, 267, 269, 275, 281, 283, 292, 297, 299 Stool, 171, 173, 262, 263, 265, 267, 299 Strand, 285, 299 Stress management, 58, 102, 299 Striatum, 278, 299 Stroke, 43, 123, 177, 184, 196, 234, 276, 299 Structure-Activity Relationship, 56, 299 Stupor, 216, 267, 275, 299 Subacute, 263, 299 Subarachnoid, 254, 258, 299 Subclinical, 42, 57, 263, 295, 299 Subiculum, 260, 300 Subspecies, 298, 300 Substance P, 252, 271, 295, 300 Substrate, 17, 36, 39, 46, 47, 55, 165, 235, 268, 300, 305 Substrate Specificity, 17, 300 Sucralfate, 170, 300 Sulfotransferases, 144, 300 Sulfur, 271, 300 Sulfuric acid, 128, 300 Supplementation, 47, 57, 101, 300 Suppression, 24, 169, 243, 300 Sympathetic Nervous System, 131, 135, 228, 237, 280, 300 Sympathomimetic, 130, 223, 246, 248, 251, 266, 277, 278, 300, 305 Symptomatic, 44, 222, 224, 225, 230, 300 Symptomatic treatment, 222, 224, 225, 230, 300 Symptomatology, 28, 46, 300 Synapses, 7, 23, 53, 131, 237, 276, 300, 301 Synapsis, 301 Synaptic, 7, 23, 24, 35, 36, 37, 47, 53, 54, 55, 128, 132, 137, 277, 297, 301 Synaptic Transmission, 47, 277, 301 Synaptic Vesicles, 132, 301 Synaptosomes, 61, 301 Synergistic, 187, 288, 301 Systolic, 261, 301 T Tachycardia, 37, 301
Index 327
Tardive, 226, 238, 301 Telecommunications, 54, 301 Temporal, 53, 223, 258, 260, 270, 301 Temporal Lobe, 223, 301 Tendinitis, 175, 301 Tenosynovitis, 175, 301 Testosterone, 292, 301 Tetracycline, 24, 301 Thalamic, 135, 251, 302 Thalamus, 246, 251, 268, 286, 302 Therapeutics, 43, 65, 73, 84, 91, 152, 163, 192, 273, 302 Thermal, 247, 277, 285, 302 Thiamine, 95, 96, 302 Thioguanine, 152, 302 Third Ventricle, 227, 251, 261, 284, 302 Thoracic, 229, 246, 302, 308 Thorax, 219, 269, 302, 306 Threonine, 296, 302 Threshold, 19, 101, 252, 261, 302 Thrombin, 253, 285, 289, 302 Thrombocytes, 285, 302 Thrombomodulin, 289, 302 Thrombosis, 57, 289, 299, 302 Thrombus, 57, 242, 263, 285, 302 Thyroid, 57, 82, 83, 85, 89, 90, 92, 101, 261, 302, 305 Thyrotropin, 261, 302 Thyroxine, 221, 283, 302 Tibial Nerve, 295, 302 Time Management, 299, 303 Tin, 135, 282, 285, 303 Tinnitus, 172, 303, 307 Tolerance, 12, 257, 303 Tomography, 36, 303 Tonic, 231, 234, 242, 303 Tonicity, 249, 303 Tooth Preparation, 220, 303 Topical, 62, 134, 150, 199, 252, 303 Torsion, 174, 263, 303 Torticollis, 174, 175, 303 Toxic, iv, 140, 144, 160, 228, 230, 238, 241, 243, 252, 262, 271, 276, 277, 303 Toxicity, 13, 19, 64, 69, 76, 78, 128, 140, 164, 234, 248, 283, 300, 303 Toxicology, 13, 28, 69, 76, 79, 170, 198, 303 Toxins, 225, 250, 259, 263, 273, 303 Trace element, 303 Trachea, 232, 267, 283, 302, 303 Tracheotomy, 177, 303 Traction, 238, 303 Tranquilizing Agents, 290, 304
Transcription Factors, 39, 115, 304 Transcutaneous, 180, 304 Transdermal, 150, 304 Transduction, 17, 53, 296, 304 Transfection, 231, 304 Transferases, 144, 304 Translation, 252, 304 Translocation, 36, 46, 47, 252, 304 Transmitter, 53, 219, 228, 248, 252, 265, 270, 277, 301, 304, 305 Trauma, 140, 244, 252, 275, 276, 304, 308 Treatment Outcome, 41, 47, 101, 304 Tremor, 174, 271, 280, 304 Triage, 44, 77, 79, 304 Trichomoniasis, 271, 304 Tricuspid Atresia, 242, 304 Trifluoperazine, 146, 304 Trigger zone, 226, 304 Trimipramine, 171, 305 Trophic, 53, 305 Tryptophan, 296, 305 Tubercle, 278, 305 Tumor Necrosis Factor, 62, 305 Type 2 diabetes, 156, 305 Tyramine, 96, 230, 273, 278, 305 Tyrosine, 63, 112, 248, 305 U Ulcer, 30, 277, 281, 300, 305 Ulcerative colitis, 152, 165, 264, 305 Umbilical Arteries, 305 Umbilical Cord, 16, 305 Unconscious, 224, 262, 305 Underachievement, 11, 305 Ureters, 305 Urethra, 281, 288, 305, 306 Uric, 257, 261, 290, 305 Urinary tract, 166, 174, 176, 246, 283, 305, 306 Urinary tract infection, 174, 176, 305 Urinary urgency, 204, 305 Urine, 28, 141, 144, 176, 180, 225, 231, 241, 247, 251, 257, 263, 277, 285, 294, 305, 306 Urodynamic, 179, 306 Urologist, 166, 306 Urology, 173, 176, 306 Urticaria, 236, 260, 306 Uterus, 236, 250, 253, 271, 279, 287, 293, 306 V Vaccine, 220, 289, 306 Vagina, 233, 236, 271, 293, 306 Vaginal, 76, 306
328 Antidepressants
Vaginitis, 233, 306 Vagus Nerve, 174, 297, 306 Vascular, 59, 82, 88, 99, 172, 222, 230, 233, 237, 250, 258, 263, 277, 284, 302, 306 Vascular Headaches, 230, 306 Vasoconstriction, 251, 306 Vasodilation, 247, 306 Vasodilator, 222, 230, 232, 248, 260, 277, 306 VE, 78, 306 Vector, 304, 306 Vein, 265, 277, 294, 305, 306 Venlafaxine, 61, 73, 75, 76, 86, 92, 112, 191, 306 Venous, 231, 289, 304, 306 Venous blood, 231, 306 Ventral, 48, 227, 261, 278, 286, 298, 306 Ventral Tegmental Area, 48, 306 Ventricle, 223, 228, 235, 242, 260, 278, 290, 301, 304, 307 Ventricular, 242, 304, 307 Venules, 231, 307 Vertebrae, 298, 307 Vertigo, 170, 172, 307 Vesicular, 26, 272, 307 Vestibular, 172, 258, 307 Vestibular Nerve, 172, 307 Vestibule, 307 Vestibulocochlear Nerve, 303, 307 Vestibulocochlear Nerve Diseases, 303, 307 Veterinary Medicine, 197, 307 Viral, 25, 27, 48, 157, 174, 250, 304, 307 Viral Load, 27, 307 Virulence, 303, 307
Virus, 82, 88, 103, 229, 235, 251, 256, 284, 304, 307 Viscera, 298, 308 Visceral, 165, 167, 198, 228, 229, 243, 268, 306, 308 Visceral Afferents, 228, 306, 308 Vitamin A, 156, 264, 308 Vitreous Body, 293, 308 Vitro, 21, 62, 64, 308 Vivo, 12, 13, 21, 33, 34, 36, 56, 308 Vocal cord, 256, 308 Volition, 265, 308 W Wakefulness, 244, 308 War, 286, 308 Watchful waiting, 44, 308 Weight Gain, 74, 133, 146, 155, 308 White blood cell, 225, 267, 269, 274, 284, 308 Windpipe, 283, 302, 308 Withdrawal, 24, 31, 133, 244, 308 Womb, 293, 306, 308 Wound Infection, 166, 308 X Xanthine, 144, 308 Xanthine Oxidase, 144, 308 Xenobiotics, 144, 308 Xenograft, 224, 308 Xerostomia, 5, 308 X-ray, 240, 254, 265, 277, 291, 294, 309 X-ray therapy, 265, 309 Y Yeasts, 233, 255, 283, 309 Z Zygote, 241, 309 Zymogen, 289, 309
Index 329
330 Antidepressants
Index 331
332 Antidepressants
