Effexor: A 3 - In- 1 Medical Reference: Medical Dictionary, Bibliography, & Annotated Research Guide

EFFEXOR A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N. P ...

Author: M.D. James N. Parker | Ph.D. Philip M. Parker

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EFFEXOR 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

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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., 1960Effexor: 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: 0-597-83594-2 1. Effexor-Popular works. I. Title.

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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.

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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 Effexor. 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.

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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.

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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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON EFFEXOR .................................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Effexor ........................................................................................... 3 E-Journals: PubMed Central ......................................................................................................... 6 The National Library of Medicine: PubMed .................................................................................. 7 CHAPTER 2. NUTRITION AND EFFEXOR .......................................................................................... 23 Overview...................................................................................................................................... 23 Finding Nutrition Studies on Effexor.......................................................................................... 23 Federal Resources on Nutrition ................................................................................................... 25 Additional Web Resources ........................................................................................................... 26 CHAPTER 3. ALTERNATIVE MEDICINE AND EFFEXOR .................................................................... 27 Overview...................................................................................................................................... 27 National Center for Complementary and Alternative Medicine.................................................. 27 Additional Web Resources ........................................................................................................... 29 General References ....................................................................................................................... 30 CHAPTER 4. CLINICAL TRIALS AND EFFEXOR ................................................................................ 31 Overview...................................................................................................................................... 31 Recent Trials on Effexor............................................................................................................... 31 Keeping Current on Clinical Trials ............................................................................................. 32 CHAPTER 5. PATENTS ON EFFEXOR................................................................................................. 35 Overview...................................................................................................................................... 35 Patents on Effexor ........................................................................................................................ 35 Patent Applications on Effexor .................................................................................................... 39 Keeping Current .......................................................................................................................... 49 CHAPTER 6. BOOKS ON EFFEXOR .................................................................................................... 51 Overview...................................................................................................................................... 51 Book Summaries: Online Booksellers........................................................................................... 51 Chapters on Effexor...................................................................................................................... 51 CHAPTER 7. PERIODICALS AND NEWS ON EFFEXOR ...................................................................... 53 Overview...................................................................................................................................... 53 News Services and Press Releases................................................................................................ 53 Academic Periodicals covering Effexor ........................................................................................ 55 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................... 57 Overview...................................................................................................................................... 57 U.S. Pharmacopeia....................................................................................................................... 57 Commercial Databases ................................................................................................................. 58 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 61 Overview...................................................................................................................................... 61 NIH Guidelines............................................................................................................................ 61 NIH Databases............................................................................................................................. 63 Other Commercial Databases....................................................................................................... 65 APPENDIX B. PATIENT RESOURCES ................................................................................................. 67 Overview...................................................................................................................................... 67 Patient Guideline Sources............................................................................................................ 67 Finding Associations.................................................................................................................... 69 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 71 Overview...................................................................................................................................... 71 Preparation................................................................................................................................... 71 Finding a Local Medical Library.................................................................................................. 71 Medical Libraries in the U.S. and Canada ................................................................................... 71

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ONLINE GLOSSARIES.................................................................................................................. 77 Online Dictionary Directories ..................................................................................................... 77 EFFEXOR DICTIONARY ............................................................................................................... 79 INDEX .............................................................................................................................................. 111

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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 Effexor 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 Effexor, 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 Effexor, 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 Effexor. 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 Effexor, 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 Effexor. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON EFFEXOR Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Effexor.

Federally Funded Research on Effexor The U.S. Government supports a variety of research studies relating to Effexor. 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 Effexor. 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 Effexor. The following is typical of the type of information found when searching the CRISP database for Effexor: •

Project Title: CBT AND VENLAFAXINE TREATMENTS FOR ANXIETY IN ALCOHOLISM Principal Investigator & Institution: Ciraulo, Domenic A. Professor of Psychiatry; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, MA 02118 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008

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).

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Summary: (provided by applicant): Deficits in anxiety management skills are frequent causes of relapse to alcohol use. Empirical data support the role of anxiety in alcohol relapse. Psychosocial and pharmacological treatments for alcohol problems increasingly address the role of negative affect in alcohol use disorders. Due to the lack of large, wellcontrolled treatment outcome trials, the optimal treatment (or combination of treatments) remains unknown. Real world practice in the treatment of alcohol use disorders frequently begins brief, intensive detoxification and stabilization, and is often followed by some combination of CBT and pharmacotherapy for patients complaining of mood difficulties while attempting early abstinence from alcohol. The proposed project is written as a "typical clinical practice" test in response to the Program Announcement PA-98-003, and is a fully-controlled trial of a combined anxiety-focused CBT and pharmacotherapy (venlafaxine; CBT-VEN) delivered for patients with comorbid alcohol-use and anxiety disorders. The CBT-VEN package will be administered in three forms depending upon the primary presenting anxiety disorder (i.e., PD, GAD, or SP) and will be contrasted with two single-active treatment conditions (CBT-PLA and REL-VEN), and one fully-controlled condition (relaxation training and placebo medication; REL-PLAC). One hundred and twenty eight participants will be recruited and, subsequent to a platform of intensive outpatient treatment for alcoholism, will be randomly assigned to a 12-week treatment condition. Both conditions will begin with a 1-week placebo run-in, and conclude with a 3-week medication taper. Follow-up assessments will be conducted at post-treatment and at 3, 6, 9, and 12-months. The longterm objectives of this research are to develop a real-world combination of psychosocial and pharmacological treatments for patients with comorbid alcohol-use and anxiety disorders that compromise prognosis, and to evaluate the effectiveness of combined psychosocial and pharmacological treatments that target anxiety among patients with this comorbidity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPARISON OF VENLAFAXINE EXTENDED RELEASE W/ PLACEBO Principal Investigator & Institution: Riddle, Mark A. Professor and Director; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: Major depression (MDD) is a significant cause of morbidity & mortality in children & adolescents. Numerous antidepressant agents have been demonstrated to have safety & efficacy in the adult population. However, there is little information on the safety & efficacy of these agents in children & adolescents. To date, only one antidepressant, fluoxetine, has demonstrated safety & efficacy for the treatment of MDD in children & adolescents. Venlafaxine, a non-specific serotonin re-uptate inhibitor, is an anti-depressant that has received FDA approval for treating depression in the adult poopulation. A formulation of extended-release venlafaxine, venlafaxine ER(V-ER), has now been developed in order to provide once-daily dosing in contrast to the BID or TID dosing of regular, or "immediate release" venlafaxine (V-IR). Preliminary studies for VER in adult patients suggest similar efficacy & possibly better tolerability than V-IR. VER is of merit in treating depression because of its mixed catecholiminergic & serotonergic activity, its relatively simple side-effect profile at recommended doses, as well as once-a-day dosing. This profile suggests V-ER is of interest in treating the pediatric population because it could have robust antidepressant qualities in addition to helping improve compliance of venlafaxine treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MARIJUANA DEPENDENCE & DEPRESSION: VENLAFAXINE TREATMENT Principal Investigator & Institution: Levin, Frances R. Q. J. Kennedy Associate Professor of Cli; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): To our knowledge there are no effective pharmacologic treatments for marijuana dependence. One subgroup that might benefit from a targeted pharmacologic intervention is marijuana-dependent individuals who have depressive disorders. The prevalence of current depression in marijuanadependent individuals in clinical samples ranges from 20-24%. This rate is substantially higher than what is found in the general population (2-10%). Given the comorbidity of depression and marijuana dependence, pharmacotherapies aimed at treating these dually-disordered patients may be particularly effective. Venlafaxine-extended release, a once-a-day medication that is commonly used to treat depression, is a promising option. Recent work completed by our group has found that a reduction in psychiatric symptoms is correlated with a reduction in substance use. However, abstinence has been more elusive. It is becoming increasingly clear that no one intervention, whether it be pharmacologic or nonpharmacologic, will be successful in treating substancedependent individuals with comorbid depression. Instead, an integrated treatment is needed. We therefore propose a placebo-controlled trial of the venlafaxine extended release, Ven-XR, an antidepressant, which is both a selective serotonin reuptake inhibitor and a noradrenergic reuptake inhibitor, in a sample of marijuana-dependent patients with current major depression. All patients in the trial will receive weekly motivational enhancement and cognitive behavior therapy. The following specific aims will be addressed: 1. To determine whether Ven-XR, along with motivational enhancement/relapse prevention therapy, reduces symptoms of depression compared to placebo. 2. To determine whether Ven-XR, along with motivational enhancement/relapse prevention therapy, increases the achievement of sustained abstinence. 3. To examine the relationship between medication treatment, mood improvement, cognitive functioning and improvement in marijuana abuse using mediational analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VENLAFAXINE FOR HOT FLASHES FOLLOWING BREAST CANCER Principal Investigator & Institution: Carpenter, Janet S. None; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-MAY-2004 Summary: Hot flashes are the most severe and fourth most prevalent menopausal symptom reported by women with breast cancer. Hot flashes affect over 65 percent of this population, with 59 percent rating the symptom as severe and 44 percent reporting they are extremely distressed by the symptom. Despite the high prevalence, severity and distress associated with this symptom, the scientific basis for managing hot flashes in women with breast cancer is limited. This randomized, double-blind, placebo-controlled crossover trial examines the effectiveness and toxicity of sustained release venlafaxine hydrochloride (37.5 mg po qd) on hot flashes in women following treatment for breast cancer. Venlafaxine is a phenylethylamine derivative that potently inhibits the reuptake of neuronal serotonin and norepinephrine and weakly inhibits the reuptake of dopamine. A secondary aim of this project is to examine the impact of hot flashes on psychological, behavioral, and physical outcomes. This study is based on the Wickham

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Symptom Management Model which depicts interrelationships between symptoms, symptom management strategies, and symptom management outcomes. Participants (n = 80) who are at least one month post-completion of surgery, radiation, and/or chemotherapy and who have been on tamoxifen (if prescribed) for at least 6 weeks will complete a 2-week baseline hot flash assessment and be randomized to one arm of the crossover trial. At the end of the first 6-week arm, participants will crossover to the opposite study arm for an additional 6 weeks. Outcomes to be assessed include effectiveness of the intervention (hot flash frequency, severity, distress and magnitude), toxicity of the intervention (subjective preference, side effects), psychological outcomes (mood disturbance), behavioral outcomes (quality of life, interference with daily activities) and physical outcomes (fatigue and sleep disturbance). Hot flashes will be measured daily, using a subjective, prospective diary methodology, and weekly, using objective state-of-the art 24-hour physiological monitoring of sternal skin conductance. Other outcomes will be measured weekly. Compliance with the intervention/placebo will be assessed weekly using medication blister pack cards. Timing of outcome assessments is based on limitations of the physiological monitoring device and expected timing of treatment effects. Summary statistics (i.e., mean, slope, maximum response, range, proportion, achievable difference) will be used to effectively reduce the design to a 2 X 2 crossover and data will be analyzed accordingly (i.e., t-tests, linear regression, GEE, mixed model). Study findings will significantly contribute to the scientific basis of hot flash management in women following treatment for breast cancer. 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 “Effexor” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for Effexor in the PubMed Central database: •

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Withdrawal reaction associated with venlafaxine. by Johnson H, Bouman WP, Lawton J. 1998 Sep 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28671

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.

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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 Effexor, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Effexor” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Effexor (hyperlinks lead to article summaries): •

A case of venlafaxine abuse. Author(s): Sattar SP, Grant KM, Bhatia SC. Source: The New England Journal of Medicine. 2003 February 20; 348(8): 764-5; Discussion 764-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594330&dopt=Abstract

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A case of venlafaxine-induced inhibition of T-lymphocyte proliferation. Author(s): Denys D, Kavelaars A, Heijnen CJ, Westenberg H. Source: Psychopharmacology. 2002 December; 164(4): 432. Epub 2002 October 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457275&dopt=Abstract

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A case report of paranoid delusion with venlafaxine use. Author(s): Iraqi AH. Source: Journal of the American Geriatrics Society. 2003 July; 51(7): 1045-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834535&dopt=Abstract

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A multinational pharmacoeconomic evaluation of acute major depressive disorder (MDD): a comparison of cost-effectiveness between venlafaxine, SSRIs and TCAs. Author(s): Doyle JJ, Casciano J, Arikian S, Tarride JE, Gonzalez MA, Casciano R. Source: Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2001 January-February; 4(1): 16-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704969&dopt=Abstract

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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.

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A pharmacokinetic drug-drug interaction study of venlafaxine and indinavir. Author(s): Levin GM, Nelson LA, DeVane CL, Preston SL, Eisele G, Carson SW. Source: Psychopharmacology Bulletin. 2001 Spring; 35(2): 62-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397887&dopt=Abstract

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A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. Author(s): Vieta E, Martinez-Aran A, Goikolea JM, Torrent C, Colom F, Benabarre A, Reinares M. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 508-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088162&dopt=Abstract

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Achieving remission from depression with venlafaxine and venlafaxine extended release: a literature review of comparative studies with selective serotonin reuptake inhibitors. Author(s): Rudolph RL. Source: Acta Psychiatrica Scandinavica. Supplementum. 2002; (415): 24-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492770&dopt=Abstract

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Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms. Author(s): Davidson JR, Meoni P, Haudiquet V, Cantillon M, Hackett D. Source: Depression and Anxiety. 2002; 16(1): 4-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203668&dopt=Abstract

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Alternative venlafaxine kinetics in overdose. Author(s): Langford NJ, Martin U, Ruprah M, Ferner RE. Source: Journal of Clinical Pharmacy and Therapeutics. 2002 December; 27(6): 465-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472987&dopt=Abstract

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An organic psychosis due to a venlafaxine-propafenone interaction. Author(s): Pfeffer F, Grube M. Source: International Journal of Psychiatry in Medicine. 2001; 31(4): 427-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949740&dopt=Abstract

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Antidepressant side effects in depression patients treated in a naturalistic setting: a study of bupropion, moclobemide, paroxetine, sertraline, and venlafaxine. Author(s): Vanderkooy JD, Kennedy SH, Bagby RM. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 March; 47(2): 174-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926080&dopt=Abstract

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Attaining remission in generalized anxiety disorder: venlafaxine extended release comparative data. Author(s): Sheehan DV. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 19: 26-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577788&dopt=Abstract

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Body weight, the tumor necrosis factor system, and leptin production during treatment with mirtazapine or venlafaxine. Author(s): Kraus T, Haack M, Schuld A, Hinze-Selch D, Koethe D, Pollmacher T. Source: Pharmacopsychiatry. 2002 November; 35(6): 220-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518269&dopt=Abstract

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Characterization of the longitudinal course of improvement in generalized anxiety disorder during long-term treatment with venlafaxine XR. Author(s): Montgomery SA, Sheehan DV, Meoni P, Haudiquet V, Hackett D. Source: Journal of Psychiatric Research. 2002 July-August; 36(4): 209-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191625&dopt=Abstract

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Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. Author(s): Kennedy SH, McCann SM, Masellis M, McIntyre RS, Raskin J, McKay G, Baker GB. Source: The Journal of Clinical Psychiatry. 2002 March; 63(3): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926715&dopt=Abstract

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Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Author(s): Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 December; 25(6): 871-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750180&dopt=Abstract

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Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression. Author(s): Stahl SM, Entsuah R, Rudolph RL. Source: Biological Psychiatry. 2002 December 15; 52(12): 1166-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488062&dopt=Abstract

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Depression-free days as a summary measure of the temporal pattern of response and remission in the treatment of major depression: a comparison of venlafaxine, selective serotonin reuptake inhibitors, and placebo. Author(s): Mallick R, Chen J, Entsuah AR, Schatzberg AF. Source: The Journal of Clinical Psychiatry. 2003 March; 64(3): 321-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716275&dopt=Abstract

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Diabetic ketoacidosis in a patient treated with olanzapine, valproic acid, and venlafaxine. Author(s): Tavakoli SA, Arguisola MS. Source: Southern Medical Journal. 2003 July; 96(7): 729-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940340&dopt=Abstract

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Disposition of venlafaxine enantiomers in rats with hepatic encephalopathy after chronic drug treatment. Author(s): Wikell C, Eap CB, Josefsson M, Apelqvist G, Ahlner J, Baumann P, Bengtsson F. Source: Chirality. 2002 May 5; 14(4): 347-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11968077&dopt=Abstract

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Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants. Author(s): Ilett KF, Kristensen JH, Hackett LP, Paech M, Kohan R, Rampono J. Source: British Journal of Clinical Pharmacology. 2002 January; 53(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849190&dopt=Abstract

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Drug-induced pneumonitis and heart failure simultaneously associated with venlafaxine. Author(s): Drent M, Singh S, Gorgels AP, Hansell DM, Bekers O, Nicholson AG, van Suylen RJ, du Bois RM. Source: American Journal of Respiratory and Critical Care Medicine. 2003 April 1; 167(7): 958-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663337&dopt=Abstract

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Effective open-label treatment of premenstrual dysphoric disorder with venlafaxine. Author(s): Hsiao MC, Liu CY. Source: Psychiatry and Clinical Neurosciences. 2003 June; 57(3): 317-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753573&dopt=Abstract

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Effectiveness of venlafaxine, extended release formulation, in the short-term and long-term treatment of generalized anxiety disorder: results of a survival analysis. Author(s): Montgomery SA, Mahe V, Haudiquet V, Hackett D. Source: Journal of Clinical Psychopharmacology. 2002 December; 22(6): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454555&dopt=Abstract

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Efficacy and safety of venlafaxine-ECT combination in treatment-resistant depression. Author(s): Gonzalez-Pinto A, Gutierrez M, Gonzalez N, Elizagarate E, Perez de Heredia JL, Mico JA. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Spring; 14(2): 206-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983797&dopt=Abstract

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Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Author(s): Smith D, Dempster C, Glanville J, Freemantle N, Anderson I. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2002 May; 180: 396-404. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983635&dopt=Abstract

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Efficacy of venlafaxine in major depression resistant to selective serotonin reuptake inhibitors. Author(s): Saiz-Ruiz J, Ibanez A, Diaz-Marsa M, Arias F, Padin J, Martin-Carrasco M, Montes JM, Ferrando L, Carrasco JL, Martin-Ballesteros E, Jorda L, Chamorro L. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452535&dopt=Abstract

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Efficacy of venlafaxine in patients with major depressive disorder who have unsustained or no response to selective serotonin reuptake inhibitors: an open-label, uncontrolled study. Author(s): Kaplan EM. Source: Clinical Therapeutics. 2002 July; 24(7): 1194-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182262&dopt=Abstract

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Erotomania induced by venlafaxine: a case study. Author(s): Adamou M, Hale AS. Source: Acta Psychiatrica Scandinavica. 2003 April; 107(4): 314-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662255&dopt=Abstract

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Even low-dose treatment of venlafaxine may provoke recurrence of hypertension in an Asian patient? Author(s): Bahk WM, Pae CU, Chae JH, Jun TY, Kim KS. Source: General Hospital Psychiatry. 2001 July-August; 23(4): 232-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11569474&dopt=Abstract

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False-positive phencyclidine immunoassay results caused by venlafaxine and Odesmethylvenlafaxine. Author(s): Sena SF, Kazimi S, Wu AH. Source: Clinical Chemistry. 2002; 48(4): 676-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901076&dopt=Abstract

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Fanconi and inappropriate secretion of antidiuretic hormone syndromes secondary to venlafaxine therapy. Author(s): Izzedine H, Launay-Vacher V, Ciroldi M, Fardet L, Deray G. Source: Nephron. 2002 December; 92(4): 944-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399647&dopt=Abstract

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Global benefit-risk assessment of antidepressants: venlafaxine XR and fluoxetine. Author(s): Entsuah R, Gorman JM. Source: Journal of Psychiatric Research. 2002 May-June; 36(3): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886688&dopt=Abstract

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Healthcare expenditure in patients treated with venlafaxine or selective serotonin reuptake inhibitors for depression and anxiety. Author(s): Wan GJ, Crown WH, Berndt ER, Finkelstein SN, Ling D. Source: Int J Clin Pract. 2002 July-August; 56(6): 434-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166541&dopt=Abstract

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Hypokalemia with venlafaxine. Author(s): Shang CY, Soong WT, Lin HN. Source: The Journal of Clinical Psychiatry. 2002 November; 63(11): 1049-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469691&dopt=Abstract

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Hyponatraemia in elderly psychiatric patients treated with Selective Serotonin Reuptake Inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit. Author(s): Kirby D, Harrigan S, Ames D. Source: International Journal of Geriatric Psychiatry. 2002 March; 17(3): 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11921151&dopt=Abstract

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Interaction between ECT and venlafaxine. Author(s): Jha A, Tomar R. Source: International Journal of Geriatric Psychiatry. 2002 October; 17(10): 979-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12325062&dopt=Abstract

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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

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Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine. Author(s): Grozinger M, Dragicevic A, Hiemke C, Shams M, Muller MJ, Hartter S. Source: Pharmacopsychiatry. 2003 January; 36(1): 3-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649767&dopt=Abstract

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Once daily sustained release tablets of venlafaxine, a novel antidepressant. Author(s): Makhija SN, Vavia PR. Source: European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V. 2002 July; 54(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084497&dopt=Abstract

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Once-daily venlafaxine extended release (XR) vs. fluoxetine for the treatment of depression. Author(s): Judge R. Source: Journal of Affective Disorders. 2001 September; 66(1): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592259&dopt=Abstract

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Open-label evaluation of venlafaxine sustained release in outpatients with generalized anxiety disorder with comorbid major depression or dysthymia: effectiveness, tolerability and predictors of response. Author(s): Perugi G, Frare F, Toni C, Ruffolo G, Torti C. Source: Neuropsychobiology. 2002; 46(3): 145-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422062&dopt=Abstract

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Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder. Author(s): Meoni P, Salinas E, Brault Y, Hackett D. Source: The Journal of Clinical Psychiatry. 2001 November; 62(11): 888-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775049&dopt=Abstract

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Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Author(s): Einarson A, Fatoye B, Sarkar M, Lavigne SV, Brochu J, Chambers C, Mastroiacovo P, Addis A, Matsui D, Schuler L, Einarson TR, Koren G. Source: The American Journal of Psychiatry. 2001 October; 158(10): 1728-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11579012&dopt=Abstract

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Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents. Author(s): Oslin DW, Ten Have TR, Streim JE, Datto CJ, Weintraub D, DiFilippo S, Katz IR. Source: The Journal of Clinical Psychiatry. 2003 August; 64(8): 875-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927001&dopt=Abstract

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Rapid onset of antidepressant activity with venlafaxine. Author(s): Weisler RH, van Meter S. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 534-5; Author Reply 535-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088168&dopt=Abstract

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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

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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

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Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. Author(s): Entsuah AR, Huang H, Thase ME. Source: The Journal of Clinical Psychiatry. 2001 November; 62(11): 869-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775046&dopt=Abstract

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Role of CYP2D6 in the stereoselective disposition of venlafaxine in humans. Author(s): Eap CB, Lessard E, Baumann P, Brawand-Amey M, Yessine MA, O'Hara G, Turgeon J. Source: Pharmacogenetics. 2003 January; 13(1): 39-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544511&dopt=Abstract

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Safety and efficacy of high dose of venlafaxine XL in treatment resistant major depression. Author(s): Mbaya P. Source: Human Psychopharmacology. 2002 October; 17(7): 335-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415551&dopt=Abstract

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Seizures associated with venlafaxine, methylphenidate, and zolpidem. Author(s): Tavakoli SA, Gleason OC. Source: Psychosomatics. 2003 May-June; 44(3): 262-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724513&dopt=Abstract

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Serotonin syndrome after single doses of co-amoxiclav during treatment with venlafaxine. Author(s): Connor H. Source: Journal of the Royal Society of Medicine. 2003 May; 96(5): 233-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724434&dopt=Abstract

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Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine. Author(s): Dougherty JA, Young H, Shafi T. Source: The Annals of Pharmacotherapy. 2002 October; 36(10): 1647-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243617&dopt=Abstract

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Serotonin syndrome induced by low-dose venlafaxine. Author(s): Pan JJ, Shen WW. Source: The Annals of Pharmacotherapy. 2003 February; 37(2): 209-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549949&dopt=Abstract

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Serotonin syndrome produced by a combination of venlafaxine and mirtazapine. Author(s): Dimellis D. Source: World J Biol Psychiatry. 2002 July; 3(3): 167. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478883&dopt=Abstract

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Serotonin toxicity with therapeutic doses of dexamphetamine and venlafaxine. Author(s): Prior FH, Isbister GK, Dawson AH, Whyte IM. Source: The Medical Journal of Australia. 2002 March 4; 176(5): 240-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999244&dopt=Abstract

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Sertralilne, paroxetine and venlafaxine in refugee post traumatic stress disorder with depression symptoms. Author(s): Smajkic A, Weine S, Duric-Bijedic Z, Boskailo E, Lewis J, Pavkovic I. Source: Med Arh. 2001; 55(1 Suppl 1): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795192&dopt=Abstract

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Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms. Author(s): Smajkic A, Weine S, Djuric-Bijedic Z, Boskailo E, Lewis J, Pavkovic I. Source: Journal of Traumatic Stress. 2001 July; 14(3): 445-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11534876&dopt=Abstract

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Severe headache with venlafaxine withdrawal. Author(s): Mayr BJ, Bonelli RM. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 1145-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841832&dopt=Abstract

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Severe hypertriglyceridemia secondary to venlafaxine and fluoxetine. Author(s): Teitelbaum M. Source: Psychosomatics. 2001 September-October; 42(5): 440-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739916&dopt=Abstract

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Shock-like sensations during venlafaxine withdrawal. Author(s): Reeves RR, Mack JE, Beddingfield JJ. Source: Pharmacotherapy. 2003 May; 23(5): 678-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741444&dopt=Abstract

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Simultaneous determination of viloxazine, venlafaxine, imipramine, desipramine, sertraline, and amoxapine in whole blood: comparison of two extraction/cleanup procedures for capillary gas chromatography with nitrogen-phosphorus detection. Author(s): Martinez MA, Sanchez de la Torre C, Almarza E. Source: Journal of Analytical Toxicology. 2002 July-August; 26(5): 296-302. Erratum In: J Anal Toxicol. 2003 March; 27(2): 8A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166817&dopt=Abstract

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Single-blind comparison of venlafaxine and nortriptyline in elderly major depression. Author(s): Gasto C, Navarro V, Marcos T, Portella MJ, Torra M, Rodamilans M. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 21-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544371&dopt=Abstract

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Social adjustment in depressed patients treated with venlafaxine and amitriptyline. Author(s): Gorenstein C, Andrade L, Moreno RA, Artes R. Source: International Clinical Psychopharmacology. 2002 July; 17(4): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131600&dopt=Abstract

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Steady-state concentration of venlafaxine enantiomers: model-based analysis of between-patient variability. Author(s): Gex-Fabry M, Rudaz S, Balant-Gorgia AE, Brachet A, Veuthey JL, Balant LP, Bertschy G. Source: European Journal of Clinical Pharmacology. 2002 August; 58(5): 323-31. Epub 2002 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185556&dopt=Abstract

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The effect of one-week treatment with venlafaxine on 35% CO2 hyperreactivity in patients with panic disorder: an open study. Author(s): Bertani A, Bellodi L, Bussi R, Caldirola D, Cucchi M, Perna G. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 106-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544387&dopt=Abstract

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The effects of venlafaxine on the subjective, reinforcing, and cardiovascular effects of cocaine in opioid-dependent and non-opioid-dependent humans. Author(s): Foltin RW, Ward AS, Collins ED, Haney M, Hart CL, Fischman MW. Source: Experimental and Clinical Psychopharmacology. 2003 May; 11(2): 123-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755456&dopt=Abstract

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The neural substrates of affective processing in depressed patients treated with venlafaxine. Author(s): Davidson RJ, Irwin W, Anderle MJ, Kalin NH. Source: The American Journal of Psychiatry. 2003 January; 160(1): 64-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505803&dopt=Abstract

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The pharmacoeconomics of venlafaxine in depression. Author(s): Morrow TJ. Source: Am J Manag Care. 2001 September; 7(11 Suppl): S386-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11570029&dopt=Abstract

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Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting. Author(s): Reis M, Lundmark J, Bjork H, Bengtsson F. Source: Therapeutic Drug Monitoring. 2002 August; 24(4): 545-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142641&dopt=Abstract

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Treatment costs of venlafaxine and selective serotonin-reuptake inhibitors for depression and anxiety. Author(s): Wan GJ, Crown WH, Berndt ER, Finkelstein SN, Ling D. Source: Manag Care Interface. 2002 June; 15(6): 24-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087603&dopt=Abstract

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Two items on the Hamilton Depression rating scale are effective predictors of remission: comparison of selective serotonin reuptake inhibitors with the combined serotonin/norepinephrine reuptake inhibitor, venlafaxine. Author(s): Silverstone PH, Entsuah R, Hackett D. Source: International Clinical Psychopharmacology. 2002 November; 17(6): 273-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409680&dopt=Abstract

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Venlafaxine and bilateral acute angle closure glaucoma. Author(s): Ng B, Sanbrook GM, Malouf AJ, Agarwal SA. Source: The Medical Journal of Australia. 2002 March 4; 176(5): 241. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999245&dopt=Abstract

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Venlafaxine and breast-feeding. Author(s): Hendrick V, Altshuler L, Wertheimer A, Dunn WA. Source: The American Journal of Psychiatry. 2001 December; 158(12): 2089-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729040&dopt=Abstract

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Venlafaxine and increased aggression in a female with autism. Author(s): Marshall BL, Napolitano DA, McAdam DB, Dunleavy III JJ, Tessing JL, Varrell J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 April; 42(4): 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649624&dopt=Abstract

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Venlafaxine- and trazodone-induced serotonin syndrome. Author(s): McCue RE, Joseph M. Source: The American Journal of Psychiatry. 2001 December; 158(12): 2088-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729039&dopt=Abstract

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Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials. Author(s): Katz IR, Reynolds CF 3rd, Alexopoulos GS, Hackett D. Source: Journal of the American Geriatrics Society. 2002 January; 50(1): 18-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028242&dopt=Abstract

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Venlafaxine for pathological crying after stroke. Author(s): Smith AG, Montealegre-Orjuela M, Douglas JE, Jenkins EA. Source: The Journal of Clinical Psychiatry. 2003 June; 64(6): 731-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823091&dopt=Abstract

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Venlafaxine for the control of hot flashes: results of a longitudinal continuation study. Author(s): Barton D, La VB, Loprinzi C, Novotny P, Wilwerding MB, Sloan J. Source: Oncology Nursing Forum. 2002 January-February; 29(1): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11817491&dopt=Abstract

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Venlafaxine in a patient with idiopathic leukopenia and mirtazapine-induced severe neutropenia. Author(s): Anghelescu I, Klawe C, Dahmen N. Source: The Journal of Clinical Psychiatry. 2002 September; 63(9): 838. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363126&dopt=Abstract

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Venlafaxine in neuropathic pain following treatment of breast cancer. Author(s): Tasmuth T, Hartel B, Kalso E. Source: European Journal of Pain (London, England). 2002; 6(1): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888224&dopt=Abstract

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Venlafaxine in the treatment of painful peripheral diabetic neuropathy in a uremic patient undergoing hemodialysis. Author(s): Yilmaz ME, Kadiroglu AK, Kara IH, Dikici S. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 August 21; 4(3): 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466766&dopt=Abstract

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Venlafaxine in the treatment of postpartum depression. Author(s): Cohen LS, Viguera AC, Bouffard SM, Nonacs RM, Morabito C, Collins MH, Ablon JS. Source: The Journal of Clinical Psychiatry. 2001 August; 62(8): 592-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561929&dopt=Abstract

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Venlafaxine in the treatment of premenstrual dysphoric disorder. Author(s): Freeman EW, Rickels K, Yonkers KA, Kunz NR, McPherson M, Upton GV. Source: Obstetrics and Gynecology. 2001 November; 98(5 Pt 1): 737-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704162&dopt=Abstract

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Venlafaxine in treatment-resistant obsessive-compulsive disorder. Author(s): Hollander E, Friedberg J, Wasserman S, Allen A, Birnbaum M, Koran LM. Source: The Journal of Clinical Psychiatry. 2003 May; 64(5): 546-50. Erratum In: J Clin Psychiatry. 2003 August; 64(8): 972. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755657&dopt=Abstract

20 Effexor

•

Venlafaxine open-label treatment of patients with obsessive-compulsive disorder. Author(s): Sevincok L, Uygur B. Source: The Australian and New Zealand Journal of Psychiatry. 2002 December; 36(6): 817. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406128&dopt=Abstract

•

Venlafaxine poisoning complicated by a late rise in creatine kinase: two case reports. Author(s): Oliver JJ, Kelly C, Jarvie D, Denieul S, Bateman DN. Source: Human & Experimental Toxicology. 2002 August; 21(8): 463-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412641&dopt=Abstract

•

Venlafaxine treatment of binge-eating disorder associated with obesity: a series of 35 patients. Author(s): Malhotra S, King KH, Welge JA, Brusman-Lovins L, McElroy SL. Source: The Journal of Clinical Psychiatry. 2002 September; 63(9): 802-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363121&dopt=Abstract

•

Venlafaxine treatment of obsessive-compulsive disorder: case reports. Author(s): Marazziti D. Source: Cns Spectr. 2003 June; 8(6): 421-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858131&dopt=Abstract

•

Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study. Author(s): Albert U, Aguglia E, Maina G, Bogetto F. Source: The Journal of Clinical Psychiatry. 2002 November; 63(11): 1004-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444814&dopt=Abstract

•

Venlafaxine versus stimulant therapy in patients with dual diagnosis ADD and depression. Author(s): Hornig-Rohan M, Amsterdam JD. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 April; 26(3): 585-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999912&dopt=Abstract

•

Venlafaxine: a new class of antidepressant. Author(s): Hardy J, Argyropoulos S, Nutt DJ. Source: Hosp Med. 2002 September; 63(9): 549-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357859&dopt=Abstract

Studies 21

•

Venlafaxine: the relationship between dose, plasma concentration and clinical response in depressive patients. Author(s): Charlier C, Pinto E, Ansseau M, Plomteux G. Source: Journal of Psychopharmacology (Oxford, England). 2002 December; 16(4): 36972. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503838&dopt=Abstract

•

Venlafaxine-associated vaginal bleeding. Author(s): Linnebur SA, Saseen JJ, Pace WD. Source: Pharmacotherapy. 2002 May; 22(5): 652-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013367&dopt=Abstract

•

Venlafaxine-induced delirium. Author(s): Howe C, Ravasia S. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 March; 48(2): 129. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655917&dopt=Abstract

•

Venlafaxine-induced galactorrhea. Author(s): Sternbach H. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 109-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544389&dopt=Abstract

•

Venlafaxine-induced hypomanic switch in bipolar depression. Author(s): Gupta N. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 October; 46(8): 760-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11692981&dopt=Abstract

23

CHAPTER 2. NUTRITION AND EFFEXOR Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Effexor.

Finding Nutrition Studies on Effexor 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 “Effexor” (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.

24 Effexor

The following information is typical of that found when using the “Full IBIDS Database” to search for “Effexor” (or a synonym): •

Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk. Author(s): Department of Pharmacology, University of Western Australia, Nedlands, Western Australia 6907 (Australia) Source: Ilett, K.F. Hackett, L.P. Dusci, L.J. Roberts, M.J. Kristensen, J.H. Paech, M. Groves, A. Yapp, P. British-Journal-of-Clinical-Pharmacology (United Kingdom). (1998). volume 45(5) page 459-462. mankind human milk breast feeding drugs excretion neurotropic drugs amines metabolites infants women disease transmission blood Summary: genre humain lait humain alimentation au sein medicament excretion medicament neurotrope amine metabolite enfant en bas age femme transmission des maladies sang

Additional physician-oriented references include: •

A pharmacokinetic drug-drug interaction study of venlafaxine and indinavir. Author(s): University of Florida, College of Pharmacy, Box 100486, Gainesville, FL, USA. [email protected] Source: Levin, G M Nelson, L A DeVane, C L Preston, S L Eisele, G Carson, S W Psychopharmacol-Bull. 2001 Spring; 35(2): 62-71 0048-5764

•

A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. Author(s): Bipolar Disorders Program, Barcelona Stanley Foundation Research Center, IDIBAPS, Hospital Clinic, University of Barcelona, Spain. [email protected] Source: Vieta, Eduard Martinez Aran, Anabel Goikolea, Jose Manuel Torrent, Carla Colom, Francesc Benabarre, Antoni Reinares, Maria J-Clin-Psychiatry. 2002 June; 63(6): 508-12 0160-6689

•

Acute effects of venlafaxine and paroxetine on serotonergic transmission in human volunteers. Author(s): Department of Neuroscience and Psychiatry, University of Newcastle, Royal Victoria Infirmary, Newcastle NE1 4LP, UK. Source: Porter, R J McAllister Williams, R H Young, A H Psychopharmacology-(Berl). 1999 September; 146(2): 194-8 0033-3158

•

Antidepressant use in the elderly. Current status of nefazodone, venlafaxine and moclobemide. Author(s): Department of Psychiatry, Rhode Island Hospital, Brown University, Providence, USA. Source: Goldberg, R J Drugs-Aging. 1997 August; 11(2): 119-31 1170-229X

•

Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo. Author(s): Cyclotron Unit, MRC CRC, Hammersmith Hospital, London, UK. [email protected] Source: Malizia, A L Melichar, J M Brown, D J Gunn, R N Reynolds, A Jones, T Nutt, D J J-Psychopharmacol. 1997; 11(3): 279-81 0269-8811

•

Effect of venlafaxine on CYP1A2-dependent pharmacokinetics and metabolism of caffeine. Author(s): Wyeth-Ayerst Laboratories, Philadelphia, USA.

Nutrition 25

Source: Amchin, J Zarycranski, W Taylor, K P Albano, D Klockowski, P M J-ClinPharmacol. 1999 March; 39(3): 252-9 0091-2700 •

Inhibition by venlafaxine of the increase in norepinephrine output in rat prefrontal cortex elicited by acute stress or by the anxiogenic drug FG 7142. Author(s): Department of Experimental Biology B. Loddo, University of Cagliari, Italy. [email protected] Source: Dazzi, L Vignone, V Seu, E Ladu, S Vacca, G Biggio, G J-Psychopharmacol. 2002 June; 16(2): 125-31 0269-8811

•

Lithium augmentation of venlafaxine: an open-label trial. Author(s): Parnassia, Psycho-Medical Centre, The Hague, The Netherlands. Source: Hoencamp, E Haffmans, J Dijken, W A Huijbrechts, I P J-Clin-Psychopharmacol. 2000 October; 20(5): 538-43 0271-0749

•

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

•

Pharmacokinetics and effect of food on the bioavailability of orally administered venlafaxine. Author(s): Clinical Pharmacokinetics Department, Wyeth-Ayerst Research, Philadelphia, Pennsylvania 19101, USA. Source: Troy, S M Parker, V P Hicks, D R Pollack, G M Chiang, S T J-Clin-Pharmacol. 1997 October; 37(10): 954-61 0091-2700

•

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

•

S33005, a novel ligand at both serotonin and norepinephrine transporters: II. Behavioral profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. Author(s): Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches de Croissy, Paris, France. [email protected] Source: Millan, M J Dekeyne, A Papp, M La Rochelle, C D MacSweeny, C Peglion, J L Brocco, M J-Pharmacol-Exp-Ther. 2001 August; 298(2): 581-91 0022-3565

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

26 Effexor

•

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/

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/

•

WebMD®Health: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

27

CHAPTER 3. ALTERNATIVE MEDICINE AND EFFEXOR Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Effexor. At the conclusion of this chapter, we will provide additional sources.

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 Effexor 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 “Effexor” (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 Effexor: •

Beyond estrogen: new alternatives for the management of hot flashes. Author(s): Dvorak SR. Source: S D J Med. 2002 January; 55(1): 11-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808405&dopt=Abstract

•

Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings. Author(s): Martin SD, Martin E, Rai SS, Richardson MA, Royall R. Source: Archives of General Psychiatry. 2001 July; 58(7): 641-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448369&dopt=Abstract

•

Changes in regional cerebral blood flow with venlafaxine in the treatment of major depression. Author(s): Davies J, Lloyd KR, Jones IK, Barnes A, Pilowsky LS.

28 Effexor

Source: The American Journal of Psychiatry. 2003 February; 160(2): 374-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562589&dopt=Abstract •

Depression in children and adolescents. Author(s): Hazell P. Source: American Family Physician. 2003 February 1; 67(3): 577-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588080&dopt=Abstract

•

Dramatic recovery of paclitaxel-disabling neurosensory toxicity following treatment with venlafaxine. Author(s): Durand JP, Goldwasser F. Source: Anti-Cancer Drugs. 2002 August; 13(7): 777-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187335&dopt=Abstract

•

Functional brain circuits in major depression and remission. Author(s): Sackeim HA. Source: Archives of General Psychiatry. 2001 July; 58(7): 649-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448370&dopt=Abstract

•

Generalized anxiety disorder in primary care: emerging issues in management and treatment. Author(s): Culpepper L. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 8: 35-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044106&dopt=Abstract

•

In vitro effects of St. John's wort extract and hyperforin on 5 HT uptake and efflux in human blood platelets. Author(s): Uebelhack R, Franke L. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S146-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518065&dopt=Abstract

•

Neuroimaging profiles and the differential therapies of depression. Author(s): Thase ME. Source: Archives of General Psychiatry. 2001 July; 58(7): 651-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448371&dopt=Abstract

•

Pharmacodynamics of venlafaxine evaluated by EEG brain mapping, psychometry and psychophysiology. Author(s): Saletu B, Grunberger J, Anderer P, Linzmayer L, Semlitsch HV, Magni G. Source: British Journal of Clinical Pharmacology. 1992 June; 33(6): 589-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1389931&dopt=Abstract

Alternative Medicine 29

•

Treatment of generalized anxiety disorder. Author(s): Gorman JM. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 8: 17-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044104&dopt=Abstract

•

Venlafaxine or bupropion responders but not nonresponders show baseline prefrontal and paralimbic hypometabolism compared with controls. Author(s): Little JT, Ketter TA, Kimbrell TA, Danielson A, Benson B, Willis MW, Post RM. Source: Psychopharmacology Bulletin. 1996; 32(4): 629-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8993084&dopt=Abstract

•

Women with PTSD: the psychodynamic aspects of psychopharmacologic and “handson” psychiatric management. Author(s): Sageman S. Source: The Journal of the American Academy of Psychoanalysis. 2002 Fall; 30(3): 41527. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389515&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

•

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/

•

WebMD®Health: 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/

30 Effexor

The following is a specific Web list relating to Effexor; 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 Depression Source: Healthnotes, Inc. www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com Eating Disorders Source: Healthnotes, Inc. www.healthnotes.com

•

Herbs and Supplements 5-HTP Source: Integrative Medicine Communications; www.drkoop.com 5-HTP Alternative names: 5-Hydroxytryptophan (5-HTP) Source: Integrative Medicine Communications; www.drkoop.com 5-Hydroxytryptophan Source: Healthnotes, Inc. www.healthnotes.com 5-Hydroxytryptophan (5-HTP) Source: Integrative Medicine Communications; www.drkoop.com 5-Hydroxytryptophan (5-HTP) Alternative names: 5-HTP Source: Integrative Medicine Communications; www.drkoop.com Antidepressants Source: Healthnotes, Inc. www.healthnotes.com Venlafaxine Source: Healthnotes, Inc. www.healthnotes.com

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.

31

CHAPTER 4. CLINICAL TRIALS AND EFFEXOR Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Effexor.

Recent Trials on Effexor The following is a list of recent trials dedicated to Effexor.8 Further information on a trial is available at the Web site indicated. •

Medroxyprogesterone Compared With Venlafaxine in Treating Hot Flashes in Women Condition(s): Hot Flashes Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Medroxyprogesterone and venlafaxine may be effective in relieving hot flashes. It is not yet known whether venlafaxine is more effective than medroxyprogesterone in relieving hot flashes. PURPOSE: Randomized phase III trial to compare the effectiveness of medroxyprogesterone with that of venlafaxine in treating women who are experiencing hot flashes. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030914

•

Multiphase Efficacy Study of venlafaxine ER to Treat Recurrent Depression Condition(s): Depression Study Status: This study is no longer recruiting patients.

8

These are listed at www.ClinicalTrials.gov.

32 Effexor

Sponsor(s): Wyeth-Ayerst Research Purpose - Excerpt: The purpose of this study is to review the long-term comparative efficacy of venlafaxine ER in achieving and sustaining remission (wellness) in patients with recurrent major depression Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046020

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 “Effexor” (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

•

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/

Clinical Trials 33

•

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

35

CHAPTER 5. PATENTS ON EFFEXOR 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 “Effexor” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Effexor, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Effexor By performing a patent search focusing on Effexor, 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

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

36 Effexor

will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on Effexor: •

Derivatives of (+)-venlafaxine and methods of preparing and using the same Inventor(s): Senanayake; Chrisantha H. (Shrewsbury, MA), Jerussi; Thomas P. (Framingham, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,197,828 Date filed: November 30, 1999 Abstract: Methods of preparing, and compositions comprising, derivatives of (+)venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders. Excerpt(s): The invention relates to optically pure derivatives of (+)-venlafaxine, methods of their synthesis, compositions comprising them, and methods of their use. A number of nontricyclic antidepressants have recently been developed that diminish the cardiovascular and anticholinergic liability characteristic of tricyclic antidepressants. Some of these compounds are used as anti-obesity agents and have shown promise in the treatment of cerebral function disorders such as Parkinson's disease and senile dementia. See e.g., WO 94/00047 and WO 94/00114. The nontricyclic compound venlafaxine, chemically named (.+-.)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol, is an antidepressant which has been studied extensively and which is described in, for example, U.S. Pat. No. 4,761,501 and Pento, J. T. Drugs of the Future 13(9):839-840 (1988). Its hydrochloride salt is currently commercially available in the United States under the trade name Effexor.RTM. Effexor.RTM., which is a racemic mixture of the (+) and (-) enantiomers of venlafaxine, is indicated for the treatment of depression. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). All of these metabolites are racemic. In vitro studies suggest that O-desmethylvenlafaxine is a more potent inhibitor of norepinephrine and dopamine uptake than the parent compound racemic venlafaxine. Muth, E. A. et al. Drug Develop. Res. 23:191-199 (1991). Odesmethylvenlafaxine has also been reported to have a half-life (t1/2) of about 10 hours, which is approximately 2.5 times as long as that of venlafaxine. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). Studies directed at understanding the activity of Odesmethylvenlafaxine as compared to its parent have been hampered, however, by the metabolic difference between laboratory animals and man in their exposure to venlafaxine. Howell, S. R. et al. Xenobiotica 24(4):315-327 (1994). Web site: http://www.delphion.com/details?pn=US06197828__

Patents 37

•

Extended release formulation of venlafaxine hydrochloride Inventor(s): Clark; John C. (Peru, NY), Sherman; Deborah M. (Plattsburgh, NY), White; Steven A. (Champlain, NY), Lamer; John U. (St. Albans, VT) Assignee(s): Wyeth (Madison, NJ) Patent Number: 6,403,120 Date filed: September 12, 2001 Abstract: This invention relates to a 24 hour extended release dosage formulation and unit dosage form thereof of venlafaxine hydrochloride, an antidepressant, which provides better control of blood plasma levels than conventional tablet formulations which must be administered two or more times a day and fiber provides a lower incidence of nausea and vomiting than the conventional tablets. More particularly, the invention comprises an extended release formulation of venlafaxine hydrochloride comprising a therapeutically effective amount of venlafaxine hydrochloride in spheroids comprised of venlafaxine hydrochloride, microcrystalline cellulose and, optionally, hydroxypropylmethylcellulose coated with a mixture of ethyl cellulose and hydroxypropylmethylcellulose. Excerpt(s): Extended release drug formulations are conventionally produced as compressed tablets by hydrogel tablet technology. To produce these sustained release tablet drug dosage forms, the active ingredient is conventionally compounded with cellulose ethers such as methyl cellulose, ethyl cellulose or hydroxypropylmethylcellulose with or without other excipients and the resulting mixture is pressed into tablets. When the tablets are orally administered, the cellulose ethers in the tablets swell upon hydration from moisture in the digestive system, thereby limiting exposure of the active ingredient to moisture. As the cellulose ethers are gradually leached away by moisture, water more deeply penetrates the gel matrix and the active ingredient slowly dissolves and diffuses through the gel, making it available for absorption by the body. An example of such a sustained release dosage form of the analgesic/anti-inflammatory drug etodolac (Lodin) appears in U.S. Pat. No. 4,966,768. U.S. Pat. No. 4,389,393 discloses sustained release therapeutic compressed solid unit dose forms of an active ingredient plus a carrier base comprised of a high molecular weight hydroxypropylmethylcellulose, methyl cellulose, sodium carboxymethylcellulose and or other cellulose ether. Where the production of tablets is not feasible, it is conventional in the drug industry to prepare encapsulated drug formulations which provide extended or sustained release properties. In this situation, the extended release capsule dosage forms may be formulated by mixing the drug with one or more binding agents to form a uniform mixture which is then moistened with water or a solvent such as ethanol to form an extrudable plastic mass from which small diameter, typically 1 mm, cylinders of drug/matrix are extruded, broken into appropriate lengths and transformed into spheroids using standard spheronization equipment. The spheroids, after drying, may then be thin-coated to retard dissolution. The fin-coated spheroids may then be placed in pharmaceutically acceptable capsules, such as starch or gelatin capsules, in the quantity needed to obtain the desired therapeutic effect. Spheroids releasing the drug at different rates may be combined in a capsule to obtain desired release rates and blood levels. U.S. Pat. No. 4,138,475 discloses a sustained release pharmaceutical composition consisting of a hard gelatin capsule filled with film-coated spheroids comprised of propanolol in admixture with microcrystalline cellulose wherein the film coating is composed of ethyl cellulose, optionally, with hydroxypropylmethylcellulose and/or a plasticizer. Venlafaxine, 1-[2(dimethylamino)-1-(4methoxyphenyl)ethyl]cyclohexanol, is an important drug in the

38 Effexor

neuropharmacological arsenal used for treatment of depression. Venlafaxine and the acid addition salts thereof are disclosed in U.S. Pat. No. 4,535,186. Venlafaxine hydrochloride is presently administered to adults in compressed tablet form in doses ranging from 75 to 350 mg/day, in divided doses two or three times a day. In therapeutic dosing with venlafaxine hydrochloride tablets, rapid dissolution results in a rapid increase in blood plasma levels of the active compound shortly after administration followed by a decrease in blood plasma levels over several hours as the active compound is eliminated or metabolized, until sub-therapeutic plasma levels are approached after about twelve hours following administration, thus requiring additional dosing with the drug. With the plural daily dosing regimen the most common side effect is nausea, experienced by about forty five percent of patients under treatment with venlafaxine hydrochloride. Vomiting also occurs in about seventeen percent of the patients. Web site: http://www.delphion.com/details?pn=US06403120__ •

Methods of treating affective disorders using derivatives of (-)-venlafaxine Inventor(s): Senanayake; Chrisantha H. (Shrewsbury, MA), Jerussi; Thomas P. (Framingham, MA), Bhongle; Nandkumar N. (Shrewsbury, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,441,048 Date filed: December 14, 2001 Abstract: Methods of preparing, and compositions comprising, derivatives of (-)venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders. Excerpt(s): The invention relates to optically pure derivatives of (-)-venlafaxine, methods of their synthesis, compositions comprising them, and methods of their use. A number of nontricyclic antidepressants have recently been developed that diminish the cardiovascular and anticholinergic liability characteristic of tricyclic antidepressants. Some of these compounds are used as anti-obesity agents and have shown promise in the treatment of cerebral function disorders such as Parkinson's disease and senile dementia. See, es., WO 94/00047 and WO 94/00114. The nontricyclic compound venlafaxine, chemically named (.+-.)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol, is an antidepressant which has been studied extensively and which is described in, for example, U.S. Pat. No. 4,761,501 and Pento, J. T. Drugs of the Future 13(9):839-840 (1988). Its hydrochloride salt is currently commercially available in the United States under the trade name Effexor.RTM. Effexor.RTM., which is a racemic mixture of the (+) and (-) enantiomers of venlafaxine, is indicated for the treatment of depression. Kuamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). All of these metabolites are racemic. In vitro studies suggest that O-desmethylvenlafaxine is a more potent inhibitor of norepinephrine and dopamine uptake than the parent compound racemic venlafaxine. Muth, E. A. et al. Drug Develop. Res. 23:191-199 (1991). Odesmethylvenlafaxine has also been reported to have a half-life (t1/2) of about 10 hours, which is approximately 2.5 times as long as that of venlafaxine. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). Studies directed at understanding the activity of Odesmethylvenlafaxine as compared to its parent have been hampered, however, by the

Patents 39

metabolic difference between laboratory animals and man in their exposure to venlafaxine. Howell, S. R. et al. Xenobiotica 24(4):315-327 (1994). Web site: http://www.delphion.com/details?pn=US06441048__ •

Osmotic device containing venlafaxine and an anti-psychotic agent Inventor(s): Vergez; Juan (Buenos Aires, AR), Faour; Joaquina (Buenos Aires, AR) Assignee(s): Osmotica Corp. (Tortola, VG) Patent Number: 6,572,890 Date filed: November 30, 2000 Abstract: The present invention provides an osmotic device containing controlled release venlafaxine in the core in combination with an anti-psychotic agent in a rapid release external coat. A wide range of anti-psychotic agents can be used in this device. Particular embodiments of the invention provide osmotic devices having predetermined release profiles. One embodiment of the osmotic device includes an external coat that has been spray-coated rather compression-coated onto the device. The device with spray-coated external core is smaller and easier to swallow than the similar device having a compression-coated external coat. The device is useful for the treatment of depression, anxiety or psychosis related disorders. Excerpt(s): This invention pertains to an osmotic device containing venlafaxine. More particularly, it pertains to an osmotic device tablet that provides a controlled release of venlafaxine, and optionally an anti-psychotic agent, following a particularly advantageous release profile. Clinical depression is a disorder characterized by low selfesteem, guilt, self-reproach, introversion, sadness, despair, sleeping disorders, eating disorders or discouragement. Depression generally causes a lower or decrease of a person's function. Anxiety is a disorder characterized by responses to anticipation of unreal or imagined danger. It manifests itself as increased heart rate, altered respiration rate, sweating, trembling, weakness, or fatigue. Psychosis is a disorder characterized by gross impairment in reality perception as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behavior without apparent awareness on the part of the person of the incomprehensibility of his behavior. Major depression and anxiety occur concomitantly in more patients than either one alone. When these disorders occur together, they are associated with more severe symptoms, increased impairment of function, a longer chronic course, poorer outcome, and a higher incidence of suicide. Web site: http://www.delphion.com/details?pn=US06572890__

Patent Applications on Effexor 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 Effexor:

10

This has been a common practice outside the United States prior to December 2000.

40 Effexor

•

Compositions of venlafaxine base Inventor(s): Oosterbaan, Marinus J. M. (Nijmegen, NL), Escoi, Juan Cucala; (Barcelona, ES), Luengo, Montserrat Gallego; (Barcelona, ES), Picha, Frantisek; (Brno, CZ) Correspondence: FLESHNER & KIM, LLP; P.O. Box 221200; Chantilly; VA; 20153-1200; US Patent Application Number: 20030190352 Date filed: March 27, 2003 Abstract: Solid venlafaxine base can be advantageously employed in making pharmaceutical compositions, especially extended release compositions. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn.119 from prior U.S. provisional application 60/367,736, filed Mar. 28, 2002, the entire contents of which are incorporated herein by reference. The present invention relates to pharmaceutical compositions using venlafaxine base, to pharmaceutically useful forms of venlafaxine base and methods of making and using the same. U.S. Pat. No. 4,535,186 describes a class of hydroxycycloalkanephenethyl amines as being useful antidepressants and exemplifies the compound now known as venlafaxine hydrochloride as one of the suitable species. Venlafaxine hydrochloride is approved for sale in various countries including the United States of America. It is available as an immediate release tablet and as an extended release capsule under the brand names EFFEXOR.RTM. (Wyeth Ayerst) and EFFEXOR ER.RTM. (Wyeth Ayerst), respectively. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Crystalline forms of venlafaxine hydrochloride Inventor(s): Szelagiewicz, Martin; (Munchenstein, CH), Van Der Schaaf, Paul Adriaan; (Allschwil, CH), Marcolli, Claudia; (Zurich, CH), Freiermuth, Beat; (Buschwiller, CH) Correspondence: CIBA SPECIALTY CHEMICALS CORPORATION; PATENT DEPARTMENT; 540 WHITE PLAINS RD; P O BOX 2005; TARRYTOWN; NY; 105919005; US Patent Application Number: 20030105359 Date filed: October 1, 2002 Abstract: Crystalline forms of Venlafaxine hydrochloride were found, referred to hereinafter as polymorphic Forms A, B and D. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and pharmaceutical compositions comprising the crystalline forms. Excerpt(s): The present invention is directed to crystalline forms of Venlafaxine hydrochloride, processes for their preparation and pharmaceutical compositions comprising these crystalline forms. Venlafaxine is an anti-depressant and acts by inhibiting synaptosomal uptake of norepinephrine (3H-NE) and serotonin (14C-5HT). Processes for the preparation of Venlafaxine hydrochloride are described in EP-A112,669 and in Yardley et al., J. Med. Chem., 1990, vol. 33, page 2899. This hydrochloride salt is desirable since it enables Venlafaxine to be conveniently formulated. There is still a need to produce Venlafaxine in a reproducible, pure and crystalline form to enable formulations to meet exacting pharmaceutical requirements and specifications. Furthermore, it is economically desirable that the product is stable for extended periods of time without the need for specialised storage conditions. The processes in the above

Patents 41

mentioned patent and publication result in the preparation of a crystalline form of Venlafaxine hydrochloride having a melting point between 215 and 217.degree. C. which is herein designated as Form C. Surprisingly, there have now been found several novel crystalline forms of Venlafaxine hydrochloride, herein designated as Form A and B, and a new crystalline hydrate of Venlafaxine hydrochloride, herein designated as Form D. The novel forms of the present invention have a good thermal stability and/or good solubility characterisitics. An additional advantage of Form B is that this form is thermodynamically more stable than the previous known Form C. herein designated as Form A. Here and in the following the abbreviations in brackets mean: (vs)=very strong intensity; (s)=strong intensity; (m)=medium intensity; (w)=weak intensity; (vw)=very weak intensity; and (sh)=shoulder. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Crystalline venlafaxine base and novel polymorphs of venlafaxine hydrochlorid, processes for preparing thereof Inventor(s): Wizel, Shlomit; (Petah Tiqva, IL), Dolitzky, Ben-Zion; (Petach Tiqva, IL), Aronhime, Judith; (Rehovot, IL), Nisnevish, Gennady; (Haifa, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20020143211 Date filed: October 19, 2001 Abstract: The present invention relates to novel essentially pure venlafaxine and the process of preparation thereof. The present invention also relates to novel solvate forms of venlafaxine hydrochloride and the process of preparation thereof. Furthermore, the present invention provides a novel process for preparing venlafaxine hydrochloride from venlafaxine; the process comprises the steps of: I) preparing a mixture of venlafaxine with acetone; and ii) exposing the mixture in gaseous hydrochloric acid. Excerpt(s): This application claims the priority of the Provisional Application Serial Nos. 60/241,577 filed Oct. 19, 2000, 60/258,861 filed Dec. 29, 2000, 60/278,721 filed Mar. 26, 2001 and 60/292,469 filed May 21, 2001. The content of these applications is herein incorporated by reference by its entireties. U.S. Pat. No. 4,535,186 (the '186 patent) describes the process for the preparation of venlafaxine hydrochloride via the intermediate venlafaxine base. The entirety of the '186 patent is incorporated herein by reference. However, the '186 patent does not describe whether the venlafaxine so obtained is solid. The existence of certain polymorphs of venlafaxine hydrochloride is mentioned in the European patent application EP 0 797 991 A1. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Enantiomers of N-desmethyl venlafaxine Inventor(s): Asselin, Andre A. (Mahwah, NJ), Yardley, John P. (King of Prussia, PA) Correspondence: WYETH; PATENT LAW GROUP; FIVE GIRALDA FARMS; MADISON; NJ; 07940; US Patent Application Number: 20020165284 Date filed: July 3, 2002

42 Effexor

Abstract: The present invention provides enantiomers of N-Desmethyl venlafaxine, as well as their use in pharmaceutical compositions and medically useful treatments, particularly including central nervous system uses. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/183,034, which was converted from U.S. patent application Ser. No. 09/333,207, filed Jun. 15, 1999, pursuant to a petition filed under 37 C.F.R. 1.53(c)(2)(i). This invention provides enantiomers of N-desmethyl venlafaxine, (R/S)-1-[1-(4-methoxyphenyl)-2(methylamino)ethyl]cyclohexanol, as well as pharmaceutical compositions and uses thereof. Various patents and literature references describe the biological activities of venlafaxine, and its salts and analogs. Venlafaxine hydrochloride tablets are marketed by Wyeth-Ayerst Laboratories under the Effexor.RTM. trademark. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Enantiomers of O-desmethyl venlafaxine Inventor(s): Asselin, Andre A. (Mahwah, NJ), Yardley, John P. (King of Prussia, PA) Correspondence: WYETH; PATENT LAW GROUP; FIVE GIRALDA FARMS; MADISON; NJ; 07940; US Patent Application Number: 20020161055 Date filed: May 23, 2002 Abstract: This invention provides pharmaceutically active enantiomers of the venlafaxine metabolite O-Desmethyl venlafaxine, R(-)-4-[2-(Dimethylamino-- 1-(1hydroxycyclo-hexyl)ethyl]phenol or R(-)1-[2-(dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclo-hexanol, and S(+)-1-[2-(Dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclohexanol or S(+)-4-[2-(Dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol, or one or more pharmaceutically acceptable salts or salt hydrates thereof, as well as pharmaceutical compositions utilizing these enantiomers and methods of using the enantiomers to treat, inhibit or control central nervous system disorders. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/183,029, which was converted from U.S. patent application Ser. No. 09/333,594, filed Jun. 15, 1999, pursuant to a petition filed under 37 C.F.R. 1.53(c)(2)(i). This invention provides enantiomers of O-desmethyl venlafaxine, (R/S) 4-[2-(Dimethylamino-1-(1hydroxycyclohexyl)ethyl]phenol, as well as pharmaceutical compositions and uses thereof. Various patents and literature references describe the biological activities of venlafaxine, and its salts and analogs. Venlafaxine hydrochloride tablets are marketed by Wyeth-Ayerst Laboratories under the Effexor.RTM. trademark. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Ethers of O-Desmethyl venlafaxine Inventor(s): Ullrich, John W. (Exton, PA), Abou-Gharbia, Magid A. (Princeton Junction, NJ), Yardley, John P. (King of Prussia, PA) Correspondence: Rebecca R. Barrett; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030158253 Date filed: December 10, 2002

Patents 43

Abstract: This invention provides O-.alpha.-acyloxyalkyl ethers of the venlafaxine metabolite 4-[2-(Dimethylamino-1-(1-hydroxycyclohexyl)ethyl]phenol, represented by Formula (I): 1wherein:the configuration at the steriogenic center (*) may be R, S, or RS (the racemate);R.sub.1 is selected from C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.6 cycloalkyl, or the moiety: 2R.sub.2 is selected from H, or C.sub.1-C.sub.6 alkyl; or,R.sub.1 and R.sub.2 may be concatenated such that 3 form a moiety having formula (b): 4R3 is selected from H or C.sub.1-C.sub.6 alkyl; andR4 and R5 are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 thioalkoxy, --CN, --OH, --CF.sub.3, --OCF.sub.3, halogen, --NH.sub.2, --NO.sub.2, or mono or dialkylamino wherein each alkyl group has 1 to 6 carbon atoms, or pharmaceutically acceptable salts or hydrates thereof, R, S, or RS forms thereof; as well as pharmaceutical compositions and methods treating central nervous system disorders. Excerpt(s): This invention provides O-.alpha.-acyloxyalkyl ethers of 4-[2(Dimethylamino-1-(1-hydroxycyclohexyl)ethyl]phenol, as well as pharmaceutical compositions and uses thereof. Various patents and literature references describe the biological activities of venlafaxine, and its salts and analogs. Venlafaxine hydrochloride tablets are marketed by Wyeth-Ayerst Laboratories as EFFEXOR. The absolute configuration of the (+) enantiomer of venlafaxine was established as S by a single crystal X-ray analysis of the hydrobromide salt and the anomalous dispersion technique (Yardley et al., J. Med. Chem., 1990, 33, 2899). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Extended release hydrochloride

composition

comprising

as

active

compound

venlafaxine

Inventor(s): Sela, Yoram; (Ra'anana, IL) Correspondence: COUDERT BROTHERS; ATTN: LEWIS REFF; 1114 AVENUE OF THE AMERICAS; NEW YORK; NY; 10036; US Patent Application Number: 20030190354 Date filed: April 3, 2003 Abstract: A composition suitable for use in making extended release tablets of venlafaxine hydrochloride is described. Excerpt(s): Venlafaxine hydrochloride is a white to off white crystalline solid with a solubility of 572 mg/ml in water (adjustment to ionic strength of 0.2 M with sodium chloride). Its octanol: water (0.2 M sodium chloride) partition coefficient 0.43. Effexor XR the brand product is formulated as an extended release capsule for once a day oral administration. Controlled or extended release dosage forms of medicaments are conventionally produced as hydrogel matrix based tablets. At this technology the controlled release dosage forms are simply prepared by mixing the active material with the appropriate rate of controlling polymers and then that mixture is compressed into the desired controlled release tablets. The rate controlling polymers are normally termed as hydrogels. Examples of such polymers are cellulose ethers such as ethyl cellulose or hydroxypropylcellulose. Patents describing preparation methods of such dosage forms are described, for example, in U.S. Pat. No. 4,966,768 or 4,389,393. In some cases, for example, with very water soluble active materials and with relatively high doses, it is not feasible to produce tablets which enable appropriate control on the drugs release. This is the case, for example with venlafaxine hydrochloride.

44 Effexor

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Extended release venlafaxine formulations Inventor(s): Lana, Inocencia Margallo; (Barcelona, ES), Platteeuw, Johannes Jan; (s'Hertogenbosch, NL), Ortega, Arturo Siles; (Barcelona, ES) Correspondence: FLESHNER & KIM, LLP; P.O. Box 221200; Chantilly; VA; 20153-1200; US Patent Application Number: 20030190351 Date filed: March 27, 2003 Abstract: A pharmaceutical composition is provided comprising venlafaxine hydrochloride and sodium carboxymethyl cellulose. The composition can be formulated to provide controlled release of the venlafaxine hydrochloride. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn.119 from prior U.S. provisional application serial No. 60/367,735, filed Mar. 28, 2002, the entire contents of which are incorporated herein by reference. The present invention relates to extended release formulations of venlafaxine hydrochloride and to the use thereof in treating various diseases or conditions. U.S. Pat. No. 4,535,186 describes a class of hydroxycycloalkanephenethyl amines as being useful antidepressants and exemplifies the compound now known as venlafaxine hydrochloride as one of the suitable species. Venlafaxine hydrochloride is approved for sale in various countries including the United States of America under the brand name EFFEXOR.RTM. (Wyeth Ayerst). It is available as an immediate release tablet and as an extended release capsule under the brand name EFFEXOR.RTM. (Wyeth Ayerst) and EFFEXOR XR.RTM. (Wyeth Ayerst), respectively. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Low water-soluble venlafaxine salts Inventor(s): Keltjens, Rolf; (Nijmegen, NL), Oosterbaan, Marinus J. M. (Nijmegen, NL) Correspondence: FLESHNER & KIM, LLP; P.O. Box 221200; Chantilly; VA; 20153-1200; US Patent Application Number: 20030190353 Date filed: March 27, 2003 Abstract: Low water soluble salts of venlafaxine, especially venlafaxine maleate, are provided. Such salts can provide a variety of dosage forms including hydrogel-based extended release dosage forms. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn.119 from U.S. provisional application serial No. 60/367,704, filed Mar. 28, 2002 and from U.S. provisional application serial No. 60/372,447, filed Apr. 16, 2002; the entire contents of each application being incorporated herein by reference. The present invention relates to low water-soluble venlafaxine salts, especially venlafaxine maleate, various forms thereof, and the use of the same in pharmaceutical compositions for treating depression and other conditions. U.S. Pat. No. 4,535,186 describes a class of hydroxycycloalkanephenethyl amines as being useful antidepressants and exemplifies the compound now known as venlafaxine hydrochloride as one of the suitable species.

Patents 45

Venlafaxine hydrochloride is approved for sale in various countries including the United States of America. It is available as an immediate release tablet and as an extended release capsule, under the brand name EFFEXOR.RTM. (Wyeth Ayerst) and EFFEXOR XR.RTM. (Wyeth Ayerst) respectively. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treating affective disorders using derivatives of (-)- venlafaxine Inventor(s): Bhongle, Nandkumar N. (Shrewsbury, MA), Senanayake, Chrisantha H. (Shrewsbury, MA), Jerussi, Thomas P. (Framingham, MA) Correspondence: PENNIE & EDMONDS LLP; 1667 K STREET NW; SUITE 1000; WASHINGTON; DC; 20006 Patent Application Number: 20020086904 Date filed: December 14, 2001 Abstract: Methods of preparing, and compositions comprising, derivatives of (-)venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders. Excerpt(s): The invention relates to optically pure derivatives of (-)-venlafaxine, methods of their synthesis, compositions comprising them, and methods of their use. A number of nontricyclic antidepressants have recently been developed that diminish the cardiovascular and anticholinergic liability characteristic of tricyclic antidepressants. Some of these compounds are used as anti-obesity agents and have shown promise in the treatment of cerebral function disorders such as Parkinson's disease and senile dementia. See, e.g., WO 94/00047 and WO 94/00114. The nontricyclic compound venlafaxine, chemically named (.+-.)-1-[2-(dimethylamino)-1-(4-m- ethoxyphenyl)ethyl]cyclohexanol, is an antidepressant which has been studied extensively and which is described in, for example, U.S. Pat. No. 4,761,501 and Pento, J. T. Drugs of the Future 13(9):839-840 (1988). Its hydrochloride salt is currently commercially available in the United States under the trade name Effexor.RTM. Effexor.RTM., which is a racemic mixture of the (+) and (-) enantiomers of venlafaxine, is indicated for the treatment of depression. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). All of these metabolites are racemic. In vitro studies suggest that O-desmethylvenlafaxine is a more potent inhibitor of norepinephrine and dopamine uptake than the parent compound racemic venlafaxine. Muth, E. A. et al. Drug Develop. Res. 23:191-199 (1991). Odesmethylvenlafaxine has also been reported to have a half-life (t{fraction (1/2)}) of about 10 hours, which is approximately 2.5 times as long as that of venlafaxine. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). Studies directed at understanding the activity of O-desmethylvenlafaxine as compared to its parent have been hampered, however, by the metabolic difference between laboratory animals and man in their exposure to venlafaxine. Howell, S. R. et al. Xenobiotica 24(4):315-327 (1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

46 Effexor

•

Methods of treating and preventing pain, anxiety, and incontinence using derivatives of (-)-venlafaxine Inventor(s): Jerussi, Thomas P. (Framingham, MA), Senanayake, Chrisantha H. (Shrewsbury, MA), Bhongle, Nandkumar N. (Shrewsbury, MA) Correspondence: PENNIE & EDMONDS LLP; 1667 K STREET NW; SUITE 1000; WASHINGTON; DC; 20006 Patent Application Number: 20030018083 Date filed: August 19, 2002 Abstract: Methods of preparing, and compositions comprising, derivatives of (-)venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders. Excerpt(s): The invention relates to optically pure derivatives of (-)-venlafaxine, methods of their synthesis, compositions comprising them, and methods of their use. A number of nontricyclic antidepressants have recently been developed that diminish the cardiovascular and anticholinergic liability characteristic of tricyclic antidepressants. Some of these compounds are used as anti-obesity agents and have shown promise in the treatment of cerebral function disorders such as Parkinson's disease and senile dementia. See, e.g., WO 94/00047 and WO 94/00114. The nontricyclic compound venlafaxine, chemically named (.+-.)-1-[2-(dimethylamino)-1-(4-m- ethoxyphenyl)ethyl]cyclohexanol, is an antidepressant which has been studied extensively and which is described in, for example, U.S. Pat. No. 4,761,501 and Pento, J. T. Drugs of the Future 13(9):839-840 (1988). Its hydrochloride salt is currently commercially available in the United States under the trade name Effexor.RTM. Effexor.RTM., which is a racemic mixture of the (+) and (-) enantiomers of venlafaxine, is indicated for the treatment of depression. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). All of these metabolites are racemic. In vitro studies suggest that O-desmethylvenlafaxine is a more potent inhibitor of norepinephrine and dopamine uptake than the parent compound racemic venlafaxine. Muth, E. A. et al. Drug Develop. Res. 23:191-199 (1991). Odesmethylvenlafaxine has also been reported to have a half-life (t1/2) of about 10 hours, which is approximately 2.5 times as long as that of venlafaxine. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). Studies directed at understanding the activity of Odesmethylvenlafaxine as compared to its parent have been hampered, however, by the metabolic difference between laboratory animals and man in their exposure to venlafaxine. Howell, S. R. et al. Xenobiotica 24(4):315-327 (1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Novel crystalline polymorph of venlafaxine hydrochloride and methods for the preparation thereof Inventor(s): Lee, Yong Jai; (Monroe, NY), Han, Jun; (Park City, IL), Ali, Kadum Abdul Nabi; (Congers, NY) Correspondence: Rebecca R. Barrett; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030109585 Date filed: December 3, 2002

Patents 47

Abstract: This invention relates to a highly thermally stable novel anhydrous crystalline polymorphic form of venlafaxine hydrochloride, methods for the preparation thereof, and its use. Excerpt(s): This application claims priority from copending provisional application serial No. 60/335,822, filed on Dec. 5, 2001, the entire disclosure of which is hereby incorporated by reference. This invention relates to a novel highly thermally stable anhydrous crystalline polymorphic form of venlafaxine hydrochloride, methods for the preparation thereof, and its use. Venlafaxine (1-[2-(dimethylamino)-1-(4methoxyphenyl)ethyl]cyclohex- anol) and its therapeutically acceptable salts (collectively referred to as venlafaxine herein) are inhibitors of monoamine neurotransmitter uptake, a mechanism associated with clinical antidepressant activity. This mechanism has also been associated with reproductive function by affecting indirectly the hypothalamic-pituitary-ovarian axis. It is believed that venlafaxine's mechanism of action is related to potent inhibition of the uptake of the monoamine neurotransmitters serotonin and norepinephrine. To a lesser degree, venlafaxine also inhibits dopamine reuptake. However, it has no inhibitory activity on monoamine oxidase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel succinate salt of O-desmethyl-venlafaxine Inventor(s): Weber, Beat T. (Zofingen, CH), Russell, Brenton W. (West Lafayette, IN), Shipplett, Rex A. (Wolcott, IN), Park, Aeri; (West Lafayette, IN), Provost, James A. (Waltham Chase, GB), Sutherland, Karen W. (New City, NY), Winkley, Michael W. (Campbell Hall, NY), Shah, Syed M. (East Hanover, NJ), Hadfield, Anthony F. (Nanuet, NY) Correspondence: WYETH; FIVE GIRALDA FARMS; MADISON; NJ; 07940; US Patent Application Number: 20030045583 Date filed: February 11, 2002 Abstract: A novel salt of O-desmethyl venlafaxine is provided, O-desmethylvenlafaxine succinate. Pharmaceutical compositions, dosage forms and methods of use are also provided. Excerpt(s): This application claims priority from copending provisional application(s) serial No. 60/268,214 filed on Feb. 12, 2001 and 60/297,963 filed on Jun. 13, 2001. The present invention provides a novel salt of O-desmethyl-venlafaxine, O-desmethylvenlafaxine succinate, as well as polymorphs, pharmaceutical compositions, dosage forms, and methods of use with the same. O-desmethyl venlafaxine is a major metabolite of venlafaxine and has been shown to inhibit norepinephrine and serotonin uptake. Klamerus, K. J. et al., "Introduction of the Composite Parameter to the Pharmacokinetics of Venlafaxine and its Active O-Desmethyl Metabolite", J. Clin. Pharmacol. 32:716-724 (1992). O-desmethyl-venlafaxine, chemically named 1-[2(dimethylamino)-1-(4-phenol)ethyl]-cyclohexanol, was exemplified as a fumarate salt in U.S. Pat. No. 4,535,186. However, the fumarate salt of O-desmethyl-venlafaxine has unsuitable physicochemical and permeability characteristics. O-desmethyl-venlafaxine is also exemplified as a free base in International Patent Publication No. WO 00/32555. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Osmotic device containing venlafaxine and an anti-psychotic agent Inventor(s): Vergez, Juan; (Buenos Aires, AR), Faour, Joaquina; (Buenos Aires, AR) Correspondence: INNOVAR, LLC; P O BOX 250647; PLANO; TX; 75025; US Patent Application Number: 20010048943 Date filed: November 30, 2000 Abstract: The present invention provides an osmotic device containing controlled release venlafaxine in the core in combination with an anti-psychotic agent in a rapid release external coat. A wide range of anti-psychotic agents can be used in this device. Particular embodiments of the invention provide osmotic devices having predetermined release profiles. One embodiment of the osmotic device includes an external coat that has been spray-coated rather compression-coated onto the device. The device with spray-coated external core is smaller and easier to swallow than the similar device having a compression-coated external coat. The device is useful for the treatment of depression, anxiety or psychosis related disorders. Excerpt(s): This invention pertains to an osmotic device containing venlafaxine. More particularly, it pertains to an osmotic device tablet that provides a controlled release of venlafaxine, and optionally an anti-psychotic agent, following a particularly advantageous release profile. Clinical depression is a disorder characterized by low selfesteem, guilt, self-reproach, introversion, sadness, despair, sleeping disorders, eating disorders or discouragement. Depression generally causes a lower or decrease of a person's function. Anxiety is a disorder characterized by responses to anticipation of unreal or imagined danger. It manifests itself as increased heart rate, altered respiration rate, sweating, trembling, weakness, or fatigue. Psychosis is a disorder characterized by gross impairment in reality perception as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behavior without apparent awareness on the part of the person of the incomprehensibility of his behavior. Major depression and anxiety occur concomitantly in more patients than either one alone. When these disorders occur together, they are associated with more severe symptoms, increased impairment of function, a longer chronic course, poorer outcome, and a higher incidence of suicide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Venlafaxine besylate Inventor(s): Escoi, Juan Cucala; (Barcelona, ES), Platteeuw, Johannes Jan; (s'Hertogenbosch, NL), Lana, Inocencia Margallo; (Barcelona, ES), Picha, Frantisek; (Brno, CZ), Luengo, Montserrat Gallego; (Barcelona, ES), Keltjens, Rolf; (Nijmegen, NL) Correspondence: FLESHNER & KIM, LLP; P.O. Box 221200; Chantilly; VA; 20153-1200; US Patent Application Number: 20030195249 Date filed: March 27, 2003 Abstract: Venlafaxine besylate compounds provide certain advantages over venlafaxine hydrochloride and are useful in forming pharmaceutical compositions and n treating venlafaxine-treatable diseases and conditions. Venlafaxine besylate can be easily formulated into an extended release dosage form including a hydrogel tablet as well as

Patents 49

other matrix-based tablet compositions. A preferred tablet making process involves hot melt granulation. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn.119 from prior U.S. provisional patent application No. 60/427,181 filed Nov. 11, 2002 and from prior U.S. provisional patent application No. 60/367,734 filed Mar. 28, 2002, the entire contents of both provisional applications being incorporated herein by reference. The present invention relates to a novel acid addition salt of venlafaxine, namely venlafaxine besylate, various forms thereof, and the use of the same in pharmaceutical compositions for treating depression and other conditions. U.S. Pat. No. 4,535,186 describes a class of hydroxycycloalkanephenethyl amines as being useful antidepressants and exemplifies the compound now known as venlafaxine hydrochloride as one of the suitable species. Venlafaxine hydrochloride is approved for sale in various countries including the United States of America. It is available as an immediate release tablet and as an extended release capsule, under the brand name EFFEXOR.RTM. (Wyeth Ayerst) and EFFEXOR XR.RTM. (Wyeth Ayerst), respectively. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Venlafaxine hydrochloride monohydrate and methods for the preparation thereof Inventor(s): Han, Jun; (Park City, IL), Lee, Yong Jai; (Monroe, NY) Correspondence: Rebecca R. Barrett; 5 Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030114536 Date filed: December 3, 2002 Abstract: This invention relates to novel crystalline polymorphic form of venlafaxine hydrochloride which exists in hydrated form (e.g., as a monohydrate), methods for the preparation thereof, and its use. Excerpt(s): This application claims priority from copending provisional application serial No. 60/335,823, filed on Dec. 5, 2001, the entire disclosure of which is hereby incorporated by reference. This invention relates to a novel crystalline polymorphic form of venlafaxine hydrochloride which exists in hydrated form (e.g., as a monohydrate), methods for the preparation thereof, and its use. Venlafaxine (1-[2(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohex- anol) and its therapeutically acceptable salts (collectively referred to as venlafaxine herein) are inhibitors of monoamine neurotransmitter uptake, a mechanism associated with clinical antidepressant activity. This mechanism has also been associated with reproductive function by affecting indirectly the hypothalamic-pituitary-ovarian axis. It is believed that venlafaxine's mechanism of action is related to potent inhibition of the uptake of the monoamine neurotransmitters serotonin and norepinephrine. To a lesser degree, venlafaxine also inhibits dopamine reuptake. However, it has no inhibitory activity on monoamine oxidase. 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 Effexor, you can access the U.S. Patent Office archive via the Internet at the following Web address:

50 Effexor

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 “Effexor” (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 Effexor. You can also use this procedure to view pending patent applications concerning Effexor. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON EFFEXOR Overview This chapter provides bibliographic book references relating to Effexor. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Effexor 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: 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 “Effexor” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Effexor” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Effexor” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Prozac and the New Antidepressants: What You Need to Know About Prozac, Zoloft, Paxil, Luvox, Wellbutrin, Effexor, Serzone, and More by William S. Appleton (1997); ISBN: 0452274435; http://www.amazon.com/exec/obidos/ASIN/0452274435/icongroupinterna

Chapters on Effexor In order to find chapters that specifically relate to Effexor, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Effexor 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 “Effexor” (or synonyms) into the “For these words:” box.

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53

CHAPTER 7. PERIODICALS AND NEWS ON EFFEXOR Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Effexor.

News Services and Press Releases One of the simplest ways of tracking press releases on Effexor 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 “Effexor” (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 Effexor. 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 “Effexor” (or synonyms). The following was recently listed in this archive for Effexor: •

Long-term venlafaxine maintains remission of depression Source: Reuters Industry Breifing Date: May 21, 2002

•

AHP Q4 profits rise 17% on robust sales of Effexor, Protonix Source: Reuters Industry Breifing Date: January 24, 2002

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•

Venlafaxine may provide rapid relief of severe PMS Source: Reuters Industry Breifing Date: November 22, 2001

•

Wyeth UK markets venlafaxine for generalized anxiety disorder Source: Reuters Medical News Date: July 16, 2001

•

American Home Product's antidepressant Effexor gets expanded indication Source: Reuters Industry Breifing Date: May 09, 2001

•

Wyeth-Ayerst's antidepressant Effexor XR wins expanded label Source: Reuters Industry Breifing Date: May 04, 2001

•

FDA cites Wyeth for misleading Effexor XR ads Source: Reuters Industry Breifing Date: October 19, 2000

•

AHP's Effexor gets FDA clearance for label change Source: Reuters Industry Breifing Date: July 18, 2000

•

Venlafaxine reduces hot flashes in breast cancer patients Source: Reuters Medical News Date: May 24, 2000

•

FDA approves venlafaxine for generalized anxiety disorder Source: Reuters Medical News Date: March 15, 1999

•

Venlafaxine comparable with fluoxetine for treatment of outpatients with major depression Source: Reuters Medical News Date: August 11, 1998 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.

Periodicals and News 55

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 “Effexor” (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 “Effexor” (or synonyms). If you know the name of a company that is relevant to Effexor, you can go to any stock trading Web site (such as http://www.etrade.com/) 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 “Effexor” (or synonyms).

Academic Periodicals covering Effexor Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Effexor. In addition to these sources, you can search for articles covering Effexor 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.”

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CHAPTER 8. 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 Effexor. 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 nonprofit 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 Effexor. 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

58 Effexor

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Effexor: 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 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.

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APPENDICES

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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 Institute11: •

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/

11

These publications are typically written by one or more of the various NIH Institutes.

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•

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 63

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •

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

12

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). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

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 NLM Gateway14 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, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Effexor” (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 673 0 24 1 3 701

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “Effexor” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

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.

Physician Resources 65

Coffee Break: Tutorials for Biologists19 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.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 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/.

19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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. 21 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.

67

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 Effexor 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 Effexor. 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 Effexor. 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 “Effexor”:

68 Effexor

•

Other guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Hormone Replacement Therapy http://www.nlm.nih.gov/medlineplus/hormonereplacementtherapy.html Menopause http://www.nlm.nih.gov/medlineplus/menopause.html Migraine http://www.nlm.nih.gov/medlineplus/migraine.html Tuberous Sclerosis http://www.nlm.nih.gov/medlineplus/tuberoussclerosis.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 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 Effexor. 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/

•

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/

Patient Resources 69

•

WebMD®Health: 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 Effexor. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Effexor. 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 Effexor. 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 “Effexor” (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 “Effexor”. 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 publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “Effexor” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

70 Effexor

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 “Effexor” (or a synonym) into the search box, and click “Submit Query.”

71

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.22

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

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

72 Effexor

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)23: •

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/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 73

•

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/

74 Effexor

•

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 75

•

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/

76 Effexor

•

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

77

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).

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

79

EFFEXOR DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] 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] 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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [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] 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 Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]

Adverse Effect: An unwanted side effect of treatment. [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

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antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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] 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] 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] 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] 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] 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: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] 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] Amoxapine: The N-demethylated derivative of the antipsychotic agent loxapine that works by blocking the reuptake of norepinephrine, serotonin, or both. It also blocks dopamine

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receptors. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anhydrous: Deprived or destitute of water. [EU] 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] 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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiuretic: Suppressing the rate of urine formation. [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] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Obesity Agents: Agents that increase energy expenditure and weight loss by neural and chemical regulation. Beta-adrenergic agents and serotoninergic drugs have been experimentally used in patients with non-insulin dependent diabetes mellitus (NIDDM) to treat obesity. [NIH] 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

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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] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] 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] Aqueous: Having to do with water. [NIH] 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] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Aspartate: A synthetic amino acid. [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] 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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [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] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bilateral: Affecting both the right and left side of body. [NIH]

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Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [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] 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] Bladder: The organ that stores urine. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blister pack: A package consisting of a clear plastic overlay affixed to a cardboard backing for protecting and displaying a product. [EU] 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] Body Fluids: Liquid components of living organisms. [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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [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] 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] 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

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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] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] 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] Carboxymethylcellulose: It is used as an emulsifier, thickener, suspending agent, etc., in cosmetics and pharmaceuticals; in research as a culture medium; in chromatography as a stabilizer for reagents; and therapeutically as a bulk laxative with antacid properties. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [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] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [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 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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [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] Cerebral: Of or pertaining of the cerebrum or the 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] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental

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protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [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]

Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [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] 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] 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] 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] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [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]

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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] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [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] 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]

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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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] 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] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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] Deamination: The removal of an amino group (NH2) from a chemical compound. [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] Delusion: A false belief, not susceptible to argument or reason, and determined, pathologically, by some form of mental disorder. [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

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relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [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] 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] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] 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] Detoxification: Treatment designed to free an addict from his drug habit. [EU] DEXA: A method (dual energy X-ray absortiometry) used to estimate total body fat and percent of body fat. Potential disadvantages include whole body radiation and the long time required for scanning while the subject lies on a hard table. [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] 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] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [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] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention

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of subsidiary means. [EU] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Horizontal: The transmission of infectious disease or pathogens from one individual to another in the same generation. [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [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] Disposition: A tendency either physical or mental toward certain diseases. [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] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several 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] 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-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug Industry: That segment of commercial enterprise devoted to the design, development, and manufacture of chemical products for use in the diagnosis and treatment of disease, disability, or other dysfunction, or to improve function. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]

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Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [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] 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

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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] Etodolac: A nonsteroidal anti-inflammatory agent with potent analgesic and antiarthritic properties. It has been shown to be effective in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and in the alleviation of postoperative pain. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [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] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] 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]

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] Flatus: Gas passed through the rectum. [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] Frail Elderly: Older adults or aged individuals who are lacking in general strength and are unusually susceptible to disease or to other infirmity. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [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] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes

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are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gestational: Psychosis attributable to or occurring during pregnancy. [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] 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] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [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] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [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] 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] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is

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usually the result of advanced liver disease. Also called hepatic coma. [NIH] 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]

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] Hydration: Combining with water. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] 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] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] 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] 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] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [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] 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 system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in

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antibody production and in measurement of antibody by the test substance. [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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [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] 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] Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [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]

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] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] 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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA

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fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [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] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loxapine: An antipsychotic agent used in schizophrenia. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH]

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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] Marijuana Abuse: The excessive use of marijuana with associated psychological symptoms and impairment in social or occupational functioning. [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] 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] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Membrane: A very thin layer of tissue that covers a surface. [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] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] 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 Processes: Conceptual functions or thinking in all its forms. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [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] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH]

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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] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Moclobemide: A reversible inhibitor of monoamine oxidase type A (RIMA) that has antidepressive properties. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired 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] 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] Mononuclear: A cell with one nucleus. [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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH]

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Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [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] 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] 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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] 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] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] 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] 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] 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

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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] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [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] 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] 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] 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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] 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

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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] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] 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] 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] 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, they do not fall into another group of products. [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] 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] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] Phenyl: Ingredient used in cold and flu remedies. [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]

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Physicochemical: Pertaining to physics and chemistry. [EU] 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]

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] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Postoperative: After surgery. [NIH] Potentiates: 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] 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] 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] 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] Premenstrual: Occurring before menstruation. [EU]

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Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] 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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [NIH]

Propanolol: Beta blocker. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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] 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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [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] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychometry: Investigation of the time factor in mental processes, mental measurement in general. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychophysiology: The study of the physiological basis of human and animal behavior. [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

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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] 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] 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] 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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [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] Radioactive: Giving off radiation. [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 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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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] 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] 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] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] 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

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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] 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] Retrospective: Looking back at events that have already taken place. [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] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] 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] Screening: Checking for disease when there are no symptoms. [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] 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] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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]

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Serotonin Syndrome: An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor. [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] 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] 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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [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] 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] 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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [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] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in

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the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [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]

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] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [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] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] 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]

Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [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] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [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] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in

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mammary and uterine. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] 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] 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] 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] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Topical: On the surface of the body. [NIH] 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] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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]

Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] 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] 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]

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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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uncontrolled study: A clinical study that lacks a comparison (i.e., a control) group. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [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] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [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] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viloxazine: A morpholine derivative used as an antidepressant. It is similar in action to imipramine. [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] 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] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [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]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as

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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]

111

INDEX A Acetone, 41, 79, 95 Acetylcholine, 79, 85, 98 Acidosis, 79, 95 Adenosine, 79, 83, 100 Adipocytes, 79, 95 Adjustment, 16, 43, 79 Adjuvant, 79, 91 Adrenal Medulla, 79, 84, 90, 98 Adrenergic, 25, 79, 80, 81, 89, 90, 106, 108 Adrenergic Agents, 79, 81 Adverse Effect, 79, 105 Afferent, 79, 95, 101 Affinity, 9, 79, 80, 82, 88, 105 Agonist, 80, 89, 106 Agoraphobia, 80, 93, 100 Alertness, 80, 83 Algorithms, 80, 83 Alkaloid, 80, 85, 97 Allylamine, 80 Alpha Particles, 80, 103 Alpha-1, 80 Alternative medicine, 55, 80 Amine, 24, 80 Amino acid, 80, 81, 82, 87, 92, 100, 102, 104, 106, 107, 108 Amitriptyline, 15, 16, 80 Ammonia, 80 Amoxapine, 16, 80 Amphetamines, 81, 85 Analgesic, 37, 81, 91, 96, 97 Anatomical, 81, 84, 94, 97 Anhydrous, 47, 81 Antagonism, 81, 83 Antibodies, 81, 92, 95 Antibody, 80, 81, 86, 92, 94, 96, 105 Anticholinergic, 36, 38, 45, 46, 80, 81 Anticonvulsant, 81, 108 Antidepressant, 4, 5, 8, 13, 14, 20, 24, 25, 36, 37, 38, 45, 46, 47, 49, 54, 80, 81, 83, 85, 91, 93, 108 Antidiuretic, 12, 81 Antigen, 79, 81, 86, 93, 94, 96, 97 Anti-inflammatory, 37, 81, 91 Anti-Obesity Agents, 36, 38, 45, 46, 81 Antipsychotic, 80, 81, 95 Antiseptic, 79, 82

Anxiety, 4, 8, 9, 11, 12, 13, 17, 18, 28, 29, 39, 46, 48, 54, 82, 99 Anxiety Disorders, 4, 82, 100 Aqueous, 82 Arterial, 80, 82, 93, 102, 106 Arteries, 82, 83, 87, 97 Arterioles, 82, 83, 84 Arteriosclerosis, 82, 93 Aspartate, 82, 95, 100 Assay, 82, 93 Astrocytes, 82, 97 Atypical, 82, 99 Auditory, 82, 101 Autonomic, 79, 82, 98, 100, 105 B Bactericidal, 82, 90 Base, 37, 40, 41, 47, 82, 87, 91, 94, 107 Behavior Therapy, 82 Benign, 82, 92 Bilateral, 18, 82 Binding agent, 37, 83 Bioavailability, 25, 83, 94 Biochemical, 83, 99, 104 Biotechnology, 6, 7, 55, 63, 83 Bladder, 83, 86, 94, 108 Blister, 6, 83 Blister pack, 6, 83 Blood Coagulation, 83, 84 Blood Platelets, 28, 83, 104 Blood pressure, 83, 93, 105 Blood vessel, 83, 84, 85, 105, 106, 107, 108 Body Fluids, 83, 105 Bowel, 83, 88, 95, 106 Bowel Movement, 83, 88, 106 Branch, 75, 83, 105, 107 Breakdown, 83, 91 Bupropion, 8, 9, 13, 29, 83 C Caffeine, 24, 83 Calcium, 83, 86 Capillary, 16, 84, 108 Capsules, 37, 84, 89, 91 Carbon Dioxide, 84, 88, 104 Carboxymethylcellulose, 37, 84 Cardiac, 80, 83, 84, 90, 97 Cardiovascular, 17, 36, 38, 45, 46, 84, 104 Case report, 7, 20, 84, 85 Catecholamine, 84, 89, 100

112 Effexor

Cell, 80, 82, 83, 84, 86, 90, 91, 94, 97, 98, 101, 102, 103, 104, 105, 107, 108 Cell Respiration, 84, 104 Cellobiose, 84 Cellulose, 37, 43, 44, 84, 101 Central Nervous System, 42, 43, 79, 81, 83, 84, 85, 88, 92, 96, 97, 104 Central Nervous System Infections, 84, 92 Cerebral, 27, 36, 38, 45, 46, 84, 87, 90, 91, 102 Cerebrum, 84 Chemotherapy, 6, 84 Chin, 84, 96 Cholesterol, 85, 106 Cholinergic, 80, 81, 85 Chronic, 10, 39, 48, 85, 94 Citalopram, 25, 85 Clear cell carcinoma, 85, 88 Clinical study, 85, 87, 108 Clinical trial, 3, 31, 32, 63, 85, 87, 89, 103 Cloning, 83, 85 Coca, 85 Cocaine, 17, 85 Cognitive behavior therapy, 5, 85 Collagen, 80, 85, 91 Comorbidity, 4, 5, 85 Complement, 86 Complementary and alternative medicine, 27, 30, 86 Complementary medicine, 27, 86 Complete remission, 86, 104 Compliance, 5, 6, 86 Compulsions, 86, 99 Computational Biology, 63, 86 Connective Tissue, 85, 86, 91 Consciousness, 81, 86, 87, 88, 89, 92, 102 Contraindications, ii, 87 Controlled clinical trial, 18, 87 Controlled study, 12, 14, 20, 87 Coronary, 87, 97 Coronary Thrombosis, 87, 97 Cortical, 87, 101, 104 Cranial, 87, 92, 100 Craniocerebral Trauma, 87, 92 Creatine, 20, 87 Creatine Kinase, 20, 87 Creatinine, 87 Curative, 87, 107 Cyclic, 83, 87 D Deamination, 87, 97 Delirium, 21, 81, 87

Delusion, 7, 87 Dementia, 36, 38, 45, 46, 81, 87 Demethylation, 13, 88 Depersonalization, 88, 100, 104 Depressive Disorder, 5, 7, 11, 14, 88 Derealization, 88, 100 DES, 24, 88 Desipramine, 16, 88 Detoxification, 4, 88 DEXA, 15, 88 Dextroamphetamine, 88, 96 Diabetes Mellitus, 81, 88, 94 Diagnostic procedure, 35, 55, 88 Dialyzer, 88, 92 Diastolic, 88, 93 Diencephalon, 88, 93, 101, 107 Digestive system, 33, 37, 88 Direct, iii, 57, 88, 89, 103, 106 Disease Transmission, 24, 89 Disease Transmission, Horizontal, 89 Disease Transmission, Vertical, 89 Disinfectant, 89, 91 Disorientation, 87, 89 Disposition, 10, 14, 89 Dissociation, 79, 89 Diuresis, 83, 89 Dizziness, 89, 100 Dopamine, 6, 25, 36, 38, 45, 46, 47, 49, 80, 81, 83, 85, 88, 89, 97, 98 Dosage Forms, 37, 43, 44, 47, 89 Double-blind, 6, 89 Drug Industry, 37, 89 Drug Interactions, 58, 89 Drug Monitoring, 17, 90 Dyskinesia, 82, 85, 90 Dysphoric, 10, 19, 88, 90 Dyspnea, 90, 100 E Eating Disorders, 30, 39, 48, 90 Efficacy, 4, 9, 11, 15, 31, 32, 90, 107 Electrolyte, 87, 90, 105 Encapsulated, 37, 90 Endogenous, 89, 90 Endorphins, 90, 98 Endotoxin, 90, 107 Energy balance, 90, 95 Enkephalins, 90, 98 Environmental Health, 62, 64, 90 Enzyme, 90, 94, 97, 102, 108 Epidermis, 83, 90 Epinephrine, 79, 89, 90, 98, 108 Esophagus, 88, 90, 106

Index 113

Estrogen, 27, 90, 104, 106 Ethanol, 37, 85, 90 Ether, 37, 91 Etodolac, 37, 91 Excipients, 37, 91 Excitation, 81, 91, 98 Expiration, 91, 104 Extracellular, 82, 86, 91, 105 Extraction, 16, 91 Extrapyramidal, 82, 89, 91 F Family Planning, 63, 91 Fat, 79, 88, 91, 95, 107 Fatigue, 6, 39, 48, 91, 92 Fissure, 91, 101 Flatus, 91 Fluoxetine, 4, 8, 9, 12, 13, 14, 16, 54, 91 Frail Elderly, 14, 91 Frontal Lobe, 91, 101 G Gallbladder, 88, 91 Gas, 16, 80, 84, 91, 93, 98 Gastric, 89, 91, 93 Gastrin, 91, 93 Gastrointestinal, 90, 91, 104, 106 Gastrointestinal tract, 90, 91, 104 Gelatin, 37, 91, 92, 106 Gene, 83, 91 Gestational, 14, 92 Gland, 79, 92, 99, 104 Glucose, 84, 88, 92, 93, 94 Glutamic Acid, 92, 98 Glycine, 80, 92, 98 Glycoprotein, 92, 107 Governing Board, 92, 101 H Half-Life, 36, 38, 45, 46, 92 Hallucinogen, 92, 100 Haptens, 79, 92 Headache, 16, 83, 92, 93 Headache Disorders, 92 Heart failure, 10, 92 Hemodialysis, 19, 88, 92 Hemorrhage, 87, 92, 106 Hemostasis, 92, 104 Hepatic, 10, 87, 92, 97 Hepatic Encephalopathy, 10, 92 Heterogeneity, 79, 93 Hormone, 12, 68, 88, 90, 91, 93, 94, 95, 96, 104 Hydration, 37, 93 Hydrochloric Acid, 41, 93

Hydrogel, 37, 43, 44, 48, 93 Hydrogen, 79, 80, 82, 93, 97, 98, 102 Hydrophilic, 93 Hypertension, 12, 92, 93 Hypertriglyceridemia, 16, 93 Hypoglycaemia, 87, 93 Hypothalamic, 47, 49, 93 Hypothalamus, 88, 93, 95 Hypoxia, 87, 93 I Id, 26, 29, 68, 74, 76, 93 Idiopathic, 19, 93 Imipramine, 16, 93, 108 Immune system, 93, 94, 95, 108 Immunoassay, 12, 93 Immunologic, 93, 94 Immunology, 79, 94 Impairment, 39, 48, 87, 90, 94, 96, 102 In vitro, 9, 28, 36, 38, 45, 46, 94 In vivo, 9, 24, 94 Incontinence, 36, 38, 45, 46, 94 Indicative, 51, 94 Indinavir, 8, 24, 94 Infarction, 87, 94, 97 Infection, 87, 94, 95, 98, 104, 108 Inflammation, 81, 94, 101, 106 Ingestion, 94, 101 Inhalation, 94, 101 Inotropic, 89, 94 Insulin, 81, 94, 95 Intoxication, 87, 94, 109 Intracellular, 83, 94, 103 Intrinsic, 80, 94 Ions, 82, 89, 90, 93, 94, 97, 105 Isoenzyme, 87, 94 K Kb, 62, 94 Ketamine, 95, 100 Ketoacidosis, 10, 79, 95 Ketone Bodies, 79, 95 Ketosis, 95 Kinetics, 8, 95 L Large Intestine, 88, 95, 103, 105 Laxative, 84, 95 Leptin, 9, 95 Leukocytes, 95, 107 Leukopenia, 19, 95 Library Services, 74, 95 Limbic, 95, 101 Limbic System, 95, 101 Liver, 88, 91, 92, 93, 95, 97

114 Effexor

Localized, 90, 94, 95, 97, 101 Loxapine, 80, 95 Lymphocyte, 7, 81, 95, 96 M Mammary, 96, 107 Mania, 96 Manic, 36, 38, 45, 46, 81, 96, 103 Manic-depressive psychosis, 96, 103 Marijuana Abuse, 5, 96 Mediate, 89, 96 Mediator, 96, 104 Medicament, 24, 96, 106 MEDLINE, 63, 96 Medroxyprogesterone, 31, 96 Membrane, 82, 86, 88, 96, 99, 105 Memory, 87, 96 Meninges, 84, 87, 96 Menopause, 68, 96 Menstruation, 96, 101 Mental, iv, 3, 11, 33, 62, 64, 84, 87, 89, 91, 96, 102, 103, 104, 105 Mental Disorders, 33, 96, 102, 103 Mental Processes, 89, 96, 102 Meperidine, 15, 96 Meta-Analysis, 11, 96 Metabolite, 10, 24, 42, 43, 47, 96, 99 Methylphenidate, 15, 96 MI, 77, 97 Microbe, 97, 107 Microglia, 82, 97 Microorganism, 97, 108 Microtubules, 97, 99 Moclobemide, 8, 24, 97 Modification, 80, 97, 103 Molecular, 37, 63, 65, 83, 86, 97, 103, 107 Molecular Structure, 97, 107 Molecule, 81, 82, 86, 89, 91, 97, 103 Monoamine, 47, 49, 88, 97, 105, 108 Monoamine Oxidase, 47, 49, 88, 97, 105, 108 Mononuclear, 97, 107 Morphine, 96, 97, 98 Motility, 97, 104 Motion Sickness, 97, 98 Myocardium, 97 N Narcolepsy, 88, 96, 98 Narcotic, 96, 97, 98 Nausea, 37, 38, 81, 89, 95, 98, 100 NCI, 1, 31, 32, 61, 98 Need, 40, 51, 69, 98 Nerve, 79, 80, 85, 96, 97, 98, 107

Nervous System, 79, 84, 96, 98, 100, 106, 108 Neural, 17, 25, 79, 81, 88, 97, 98, 105 Neuromuscular, 79, 98, 105 Neuronal, 6, 9, 85, 98 Neurons, 85, 98, 106 Neuropathy, 19, 98 Neurotransmitter, 47, 49, 79, 80, 89, 92, 98, 106, 108 Neutrons, 80, 98, 103 Nitrogen, 16, 80, 98, 107 Nonverbal Communication, 98, 103 Norepinephrine, 6, 9, 18, 25, 36, 38, 40, 45, 46, 47, 49, 79, 80, 88, 89, 98 Nortriptyline, 16, 99 Nucleic acid, 98, 99 Nucleus, 87, 97, 98, 99, 101, 102 O Obsessive-Compulsive Disorder, 19, 20, 99 Ointments, 89, 99 Osmosis, 99 Osmotic, 39, 48, 99 Osteoarthritis, 91, 99 Outpatient, 4, 99 Overdose, 8, 14, 99 Oxygen Consumption, 99, 104 P Paclitaxel, 28, 99 Palliative, 99, 107 Pancreas, 88, 94, 99 Panic, 17, 93, 99 Panic Disorder, 17, 93, 99 Paresthesias, 100 Paroxetine, 8, 9, 15, 16, 24, 100 Partial remission, 100, 103 Peptide, 80, 95, 100, 102 Perception, 39, 48, 88, 100, 104 Peripheral Nervous System, 90, 98, 100, 106 Pharmaceutical Preparations, 84, 91, 100 Pharmaceutical Solutions, 89, 100 Pharmacokinetic, 8, 9, 24, 100 Pharmacologic, 5, 92, 100, 107 Pharmacotherapy, 4, 15, 16, 21, 100 Phencyclidine, 12, 100 Phenyl, 96, 100 Phosphorus, 16, 84, 100 Physicochemical, 47, 101 Physiologic, 80, 92, 96, 101, 103 Plants, 80, 84, 85, 92, 99, 101 Plasma, 21, 37, 38, 81, 91, 92, 101

Index 115

Pneumonia, 87, 101 Pneumonitis, 10, 101 Poisoning, 20, 87, 94, 98, 101 Polymers, 43, 101, 102 Polymorphic, 40, 47, 49, 101 Polysaccharide, 81, 84, 101 Postoperative, 91, 96, 101 Potentiates, 88, 101 Potentiating, 80, 101 Practicability, 101, 107 Practice Guidelines, 64, 101 Precursor, 89, 90, 98, 101, 107, 108 Prefrontal Cortex, 25, 101 Premenstrual, 10, 19, 101 Presynaptic, 98, 102 Prevalence, 5, 102 Prognostic factor, 102, 106 Progressive, 88, 99, 102, 104 Projection, 99, 101, 102 Propafenone, 8, 102 Propanolol, 37, 102 Protease, 94, 102 Protein S, 83, 102 Proteins, 80, 81, 85, 86, 87, 97, 98, 100, 101, 102, 103, 105 Protons, 80, 93, 102, 103 Proto-Oncogene Proteins, 99, 102 Proto-Oncogene Proteins c-mos, 99, 102 Psychiatric, 5, 9, 12, 14, 29, 96, 102 Psychiatry, 3, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 24, 27, 28, 29, 102 Psychic, 96, 102, 104 Psychoactive, 102, 109 Psychometry, 28, 102 Psychomotor, 87, 102 Psychophysiology, 28, 102 Psychosis, 8, 39, 48, 81, 92, 102 Psychotherapy, 27, 85, 103 Public Policy, 63, 103 Q Quality of Life, 6, 103 R Race, 17, 36, 38, 45, 46, 103 Racemic, 17, 36, 38, 45, 46, 103 Radiation, 6, 88, 103 Radioactive, 92, 93, 103 Randomized, 6, 8, 14, 18, 24, 31, 90, 103 Randomized clinical trial, 14, 103 Reagent, 93, 103 Reality Testing, 102, 103 Receptor, 9, 81, 89, 103, 104, 105 Receptors, Serotonin, 103, 104

Rectum, 83, 88, 91, 94, 95, 103, 106 Recurrence, 12, 96, 103 Refer, 1, 86, 89, 90, 98, 103 Regimen, 38, 90, 100, 103 Relapse, 4, 5, 103 Remission, 8, 9, 10, 14, 18, 28, 32, 53, 96, 103 Renal failure, 87, 104 Respiration, 39, 48, 84, 104 Retrospective, 12, 104 Rheumatoid, 91, 104 Rheumatoid arthritis, 91, 104 S Salivary, 88, 104 Salivary glands, 88, 104 Schizoid, 104, 109 Schizophrenia, 95, 104, 109 Schizotypal Personality Disorder, 88, 104, 109 Screening, 85, 104 Secretion, 12, 97, 104 Sedative, 80, 93, 104 Seizures, 15, 87, 104 Selective estrogen receptor modulator, 104, 106 Senile, 36, 38, 45, 46, 104 Serologic, 93, 104 Serotonin Syndrome, 18, 105 Sertraline, 8, 14, 16, 105 Serum, 86, 87, 104, 105, 107 Side effect, 6, 8, 13, 38, 57, 79, 82, 85, 105, 107 Signs and Symptoms, 103, 105 Skeletal, 87, 105 Skull, 87, 105, 107 Small intestine, 93, 105 Smoking Cessation, 83, 105 Smooth muscle, 80, 81, 83, 97, 105, 106 Social Environment, 103, 105 Sodium, 37, 43, 44, 105, 108 Sodium Channels, 105, 108 Solvent, 37, 79, 91, 99, 100, 105 Somatic, 95, 100, 101, 105 Specialist, 69, 105 Species, 40, 44, 49, 89, 90, 103, 105, 106, 108 Specificity, 80, 105 Spinal cord, 82, 84, 85, 96, 98, 100, 105 Spondylitis, 91, 106 Stabilization, 4, 106 Stabilizer, 84, 106 Stimulant, 20, 83, 88, 96, 106

116 Effexor

Stomach, 88, 90, 91, 93, 95, 98, 105, 106 Stool, 94, 95, 106 Stress, 15, 16, 25, 84, 98, 104, 106 Stroke, 18, 33, 62, 106 Subarachnoid, 92, 106 Subspecies, 105, 106 Substance P, 96, 104, 106 Suppositories, 91, 106 Survival Analysis, 11, 106 Sympathomimetic, 88, 89, 90, 99, 106, 108 Synapse, 79, 88, 102, 106, 107 Synaptic, 98, 106 Systemic, 58, 83, 87, 90, 94, 106 Systolic, 93, 106 T Tamoxifen, 6, 104, 106 Tardive, 82, 85, 107 Temporal, 10, 92, 107 Thalamus, 88, 95, 101, 107 Therapeutics, 8, 11, 58, 97, 107 Thermal, 41, 89, 98, 107 Threshold, 93, 107 Thrombosis, 102, 106, 107 Tissue, 79, 81, 82, 83, 84, 86, 87, 90, 93, 96, 97, 98, 104, 105, 106, 107 Topical, 90, 107 Toxic, iv, 98, 107 Toxicity, 6, 14, 15, 28, 89, 107 Toxicology, 16, 20, 64, 107 Transfection, 83, 107 Transmitter, 79, 82, 89, 96, 99, 107, 108

Trauma, 87, 107 Treatment Outcome, 4, 107 Tricyclic, 14, 36, 38, 45, 46, 80, 85, 88, 93, 107 Triglyceride, 93, 107 Tryptophan, 85, 104, 107 Tumor Necrosis Factor, 9, 107 Tyramine, 97, 108 Tyrosine, 89, 108 U Unconscious, 93, 108 Uncontrolled study, 11, 108 Urinary, 94, 108 Urine, 81, 83, 87, 89, 94, 95, 108 V Vagina, 88, 96, 108 Vaginal, 21, 108 Valproic Acid, 10, 108 Vasodilator, 89, 108 Ventricular, 102, 108 Venules, 83, 84, 108 Veterinary Medicine, 63, 108 Viloxazine, 16, 108 Virulence, 107, 108 Vitro, 108 Vivo, 108 W Wakefulness, 87, 108 Weight Gain, 36, 38, 45, 46, 108 White blood cell, 81, 95, 108 Withdrawal, 6, 16, 87, 96, 108

Index 117

118 Effexor

Index 119

120 Effexor

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