BUPROPION 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., 1960Bupropion: 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: 0-597-83578-0 1. Bupropion-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.
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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 bupropion. 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 BUPROPION .............................................................................................. 3 Overview ....................................................................................................................................... 3 The Combined Health Information Database ................................................................................ 3 Federally Funded Research on Bupropion ................................................................................... 12 E-Journals: PubMed Central ....................................................................................................... 58 The National Library of Medicine: PubMed................................................................................ 59 CHAPTER 2. NUTRITION AND BUPROPION................................................................................... 121 Overview ................................................................................................................................... 121 Finding Nutrition Studies on Bupropion.................................................................................. 121 Federal Resources on Nutrition................................................................................................. 125 Additional Web Resources......................................................................................................... 125 CHAPTER 3. ALTERNATIVE MEDICINE AND BUPROPION ............................................................ 127 Overview ................................................................................................................................... 127 National Center for Complementary and Alternative Medicine ............................................... 127 Additional Web Resources......................................................................................................... 130 General References..................................................................................................................... 131 CHAPTER 4. DISSERTATIONS ON BUPROPION .............................................................................. 133 Overview ................................................................................................................................... 133 Dissertations on Bupropion....................................................................................................... 133 Keeping Current ........................................................................................................................ 133 CHAPTER 5. CLINICAL TRIALS AND BUPROPION ......................................................................... 135 Overview ................................................................................................................................... 135 Recent Trials on Bupropion....................................................................................................... 135 Keeping Current on Clinical Trials ........................................................................................... 140 CHAPTER 6. PATENTS ON BUPROPION ......................................................................................... 143 Overview ................................................................................................................................... 143 Patents on Bupropion ................................................................................................................ 143 Patent Applications on Bupropion ............................................................................................ 160 Keeping Current ........................................................................................................................ 165 CHAPTER 7. BOOKS ON BUPROPION ............................................................................................. 167 Overview ................................................................................................................................... 167 Chapters on Bupropion.............................................................................................................. 167 CHAPTER 8. PERIODICALS AND NEWS ON BUPROPION ............................................................... 169 Overview ................................................................................................................................... 169 News Services and Press Releases ............................................................................................. 169 Newsletter Articles .................................................................................................................... 174 Academic Periodicals covering Bupropion ................................................................................ 175 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 179 Overview ................................................................................................................................... 179 NIH Guidelines ......................................................................................................................... 179 NIH Databases .......................................................................................................................... 181 Other Commercial Databases .................................................................................................... 185 APPENDIX B. PATIENT RESOURCES .............................................................................................. 187 Overview ................................................................................................................................... 187 Patient Guideline Sources ......................................................................................................... 187 Finding Associations ................................................................................................................. 189 APPENDIX C. FINDING MEDICAL LIBRARIES ............................................................................... 191 Overview ................................................................................................................................... 191 Preparation ................................................................................................................................ 191 Finding a Local Medical Library ............................................................................................... 191
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Medical Libraries in the U.S. and Canada .................................................................................191 ONLINE GLOSSARIES ................................................................................................................197 Online Dictionary Directories ...................................................................................................197 BUPROPION DICTIONARY.......................................................................................................199 INDEX...............................................................................................................................................239
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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 bupropion 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 bupropion, 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 bupropion, 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 bupropion. 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 bupropion, 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 bupropion. 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 BUPROPION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bupropion.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and bupropion, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “bupropion” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Mood Disorders in Rheumatic Disease: Evaluation and Management Source: Journal of Musculoskeletal Medicine. 16(11): 643-646,648-650. November 1999. Summary: This journal article provides health professionals with information on the diagnosis of mood disorders that commonly occur in people who have rheumatic diseases and the therapeutic strategies that may help patients better cope with the stress of chronic illness. Mood disorders are common in people who have rheumatic diseases such as fibromyalgia, rheumatoid arthritis, and systemic lupus erythematous. Altered mood tends to worsen as the illness becomes more severe. Major depression is particularly common. The presence of depressed mood, loss of interest or pleasure for 2 weeks or more, and at least five of nine established criteria such as weight change, fatigue, and indecisiveness is diagnostic. Other mood disorders that people who have a rheumatic disease may experience include minor depression, adjustment disorder with
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depressed mood, bereavement, bipolar disorder, and depressive disorder related to the general medical condition. Management includes a combination of biologic and interactive approaches. The goals of treatment are to restore normal mood, prevent suicide, and improve self esteem, productivity, and quality of life. Pharmacologic treatment of depression is an essential component of care and is usually successful. Psychopharmacologic agents include selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine inhibitors, psychostimulants, mood stabilizers, lithium, and newer agents such as bupropion. Electroconvulsive therapy is a treatment option commonly used for patients with severe, life threatening depression or psychotic depression and for patients in whom drug therapy is considered dangerous. Two major forms of psychotherapy are effective in treating patients who have major depression associated with rheumatic disease and other medical illness. Cognitive behavioral therapy deals with the relationship between cognition, affect, and behavior, whereas interpersonal therapy deals with interpersonal relationships and their effects on mood. Although many mood disorders can be managed satisfactorily within the primary care setting, referral is recommended for patients who are at significant risk for suicide or who have psychosis, psychotic depression, or full blown mania. 3 tables and 25 references. (AA-M). •
Exercise: The Healthy Alternative to Smoking Source: Diabetes Forecast. 55(5): 30-32. May 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article helps readers with diabetes understand why smoking is a particularly bad habit for them. The author explains how smoking affects the blood cells, which are already under stress from the effect of diabetes and its accompanying hyperglycemia (high blood glucose levels). People with diabetes who smoke face other risks as well. Smoking increases cholesterol and blood pressure levels, and directly damages and constricts blood vessels. Smoking also limits joint mobility, which can become especially problematic if the person has long standing diabetes and is already predisposed to arthritis and other limitations in motion. The author then proposes that, as a strategy to help with quitting smoking, readers begin an exercise program. Beginning an exercise program while trying to quit smoking is a great way to replace an old addiction with a new, healthier, habit. The author also discusses the role of nicotine replacement (gum or patch) and the medication bupropion (Zyban) as other options to help with the quitting process.
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Smoking Cessation: Integrating Recent Advances Into Clinical Practice Source: Thorax. 56(7):579-582, July 2001. Summary: The author reviews the role of treatments for nicotine addiction in the management of smoking cessation and discusses how new United Kingdom smoking cessation services should best be utilized. Effective smoking cessation interventions available to physicians include (1) brief counseling, (2) intensive counseling, (3) nicotine replacement therapy (NRT), (4) bupropion, and (5) nortriptyline. There is much more evidence for NRT than for bupropion and nortriptyline. Brief antismoking advice has been shown to be effective, especially when given periodically instead of at every consultation. Intensive antismoking advice is marginally more effective than brief antismoking advice. There is strong evidence from many trials that NRT given for at least 8 weeks is an effective therapy in conjunction with advice given by physicians.
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However, NRT is only effective if used by heavier smokers, and its effect is probably maximized when behavioral support is provided. It is not known how the antidepressant bupropion works, but it decreases the withdrawal symptoms that smokers experience when quitting smoking. Two trials have indicated that nortriptyline is also effective in smoking cessation, but this antidepressant has not been licensed for use in smoking cessation in the United Kingdom. In 1999, funds were made available to develop smoking cessation services in the United Kingdom. These services are allowed to issue smokers with NRT free of charge. The author concludes with a list of four recommendations for using antismoking interventions: (1) Systematically record smoking status, (2) offer at least brief advice against smoking to motivated light smokers, (3) offer NRT to motivated heavy smokers who smoke more than 10 cigarettes daily, and (4) offer NRT and bupropion to heavy smokers who smoke more than 15 cigarettes daily. 1 table, 24 references. •
Clinician Perseverance: Helping Patients Overcoming Tobacco Dependence Source: Wisconsin Medical Journal. 100(3):14-15, 2001. Summary: The authors discuss the importance of clinician perseverance in helping patients overcoming tobacco dependence. In 1996, The Smoking Cessation Clinical Practice Guideline (AHCPR) was released. It evaluated the literature on promoting cessation and provided clinicians with strategies for helping patients interested in quitting smoking. These strategies included identification of tobacco users and offering smoking cessation at every office visit and every hospital admission for every smoker. The AHCPR was updated at the University of Wisconsin's Center for Tobacco Research and Intervention and released in 2000 as a Public Health Service Report: Treating Tobacco Use and Dependence. A key point in this report is that tobacco dependence is a chronic disease. It implies that relapse is expected for those who quit smoking. Over 70 percent of smokers have tried to quit in their lifetimes. The average smoker tries to quit four to seven times. Smokers often feel like failures and physicians trying to help them may feel like they have nothing more to offer the patient who has relapsed many times. Physicians should consider treatment of tobacco dependence in the same paradigm as treatment of other chronic conditions. Appropriate management of chronic conditions requires a collaborative effort between patient and physician. The physician must be committed to providing long-term counseling, support, and reinforcement of treatment at each visit. Physicians may also need to be prepared to refer smokers to specialists and to recommend and prescribe medication such as bupropion and nicotine replacement therapy. The author concludes that it is up to each clinician to put the Guideline into practice and persevere with patients.
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State Report: Medicaid Coverage for Tobacco-dependence Treatments Source: Health Affairs. 20(1):298-303, January-February 2001. Summary: Researchers summarize and discuss the results of a survey of states providing treatment for tobacco dependency under their Medicaid programs. The survey focused on determining whether each state's program met the Agency for Health Care Policy and Research (AHCPR) clinical practice guideline that states that Medicaid and other programs cover various aspects of nicotine replacement therapy (NRT) and counseling. A questionnaire asking about details of Medicaid coverage of tobacco dependency treatment was sent to Medicaid program directors in the 50 states and the District of Columbia (DC) in 1998. The questionnaire specifically asked about (1) which pharmacotherapy treatments were covered; (2) whether comprehensive benefits (including all forms of NRT, bupropion, and group and individual counseling) were
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offered; (3) whether the program met AHCPR guidelines; (4) other treatment interventions, such as programs for women who are pregnant or breast feeding); and (5) factors associated with treatment coverage, such as smoking prevalence. All but one state responded. Twenty-four states plus DC covered one or more treatments for tobacco dependency in their Medicaid programs. Of the states providing Medicaid coverage, 22 states and DC covered some aspect of NRT, usually the nicotine patch, gum, and/or nasal spray. Only 10 states covered any form of counseling. Six states offered comprehensive Medicaid benefits for treating tobacco dependency. Medicaid directors in 28 states and DC were aware of the AHCPR guidelines; however, only four states based their benefits on the guidelines. Only four states offered any special programs designed to assist pregnant or breast-feeding women to quit smoking. Only about one-third of the 14 states with the highest rates of smoking (at least 25 percent of the adult population smoking) provided NRT or smoking cessation counseling. States that are major growers of tobacco were less likely to provide Medicaid coverage for tobacco dependency treatments. Researchers conclude that coverage and reimbursement policies in state Medicaid programs have not kept pace with the growing evidence base for tobacco dependence treatments. Most are failing to cover services that are effective in populations that need them the most. It is in the interest of the public's health and the most efficient use of government resources for state Medicaid programs to use the existing evidence base for establishing coverage for tobacco dependency treatments. 1 table, 14 references. •
Techniques for Smoking Cessation: What Really Works? Source: Texas Medicine. 97(2):63-67, February 2001. Summary: The author discusses effective techniques for smoking cessation that can be used by primary care physicians (PCP's) to promote smoking cessation among their patients. Topics include (1) the characteristics of nicotine dependency, (2) strategies to help patients quit smoking, and (3) the stages of change of a patient contemplating stopping smoking. Brief counseling-based smoking cessation interventions (that take less than 3 minutes) offered in the context of an office or hospital visit have been shown to be effective in encouraging patients to stop smoking. These interventions are most likely to succeed when the physician correctly identifies the patient's stage of readiness to change and focuses the intervention on moving the patient toward quitting by taking one stage at a time. The author describes specific counseling strategies that can be used for the precontemplation, contemplation, and preparation stages of change. Once a patient has progressed to the preparation stage and has set a quit date, he/she becomes a good candidate for medication to treat nicotine withdrawal and craving. Medicationbased approaches include nicotine replacement therapy and bupropion. 1 figure, 16 references.
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Direct Observation of Smoking Cessation Activities in Primary Care Practice Source: Journal of Family Practice. 50(8):688-693, August 2001. Summary: Researchers investigated how often family physicians incorporated smoking cessation efforts into their patients' routine office visits and examined the effect of physician, patient, and office characteristics on the frequency of these efforts. Participants were people seen for routine office visits in 38 primary care physician practices. Researchers collected data using direct observation of physician-patient encounters, a physician survey, and an on-site examination of office systems for supporting smoking cessation. Study outcomes were the frequency of tobacco discussions among all patients, the extent of these discussions among people who were
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smokers, and the presence of tobacco-related systems and policies in physicians' offices. Data analysis indicated that physicians discussed tobacco during 633 of the 2,963 encounters with patients. Discussing tobacco was more common in the 58 percent of practices that had standard forms for recording smoking status. These discussions were also more common during new patient visits, although they occurred less often with older patients and among physicians who had been in practice more than 10 years. Of the 244 identified smokers, physicians provided assistance with smoking cessation for 39 percent. They discussed bupropion and nicotine-replacement therapy with smokers in 31 percent and 17 percent of the cases, respectively. Although 68 percent of the offices had smoking cessation materials for their patients, few recorded tobacco use in the vital signs section of the patient history or assigned smoking-related tasks to nonphysician staff. The researchers conclude that smoking cessation practices vary widely in primary care offices and they recommend strategies to help physicians incorporate systematic approaches to maximize smoking cessation rates. 1 figure, 3 tables, 29 references. •
II. Smoking Cessation in the Hospital Setting: A New Opportunity for Managed Care: Introduction Source: Tobacco Control. 9(Supplement 1):i54-i56, 2000. Summary: The author introduces a discussion of the delivery of smoking cessation interventions by managed care organizations. Although most efforts have focused on outpatient settings, smoking interventions delivered in hospitals and other sites treating patients with chronic medical illness may be particularly effective. The value of this idea has been demonstrated over the past decade. Programs designed for patients recovering from myocardial infarction have produced the best results; they have doubled the smoking cessation rate of postmyocardial infarction patients. Effective programs already share these common elements: (1) Systematic identification of smokers at or shortly after admission; (2) a bedside counseling session by a nurse or specially trained counselor, often supplemented by written or audiovisual material; (3) physician advice to stop smoking; and (4) continued contact, usually by telephone, for at least 3 months after discharge. They do not yet systematically incorporate drugs, such as nicotine replacement or bupropion, that boost smoking cessation rates in ambulatory settings. Managed care organizations need not wait to take action. Since 1996, the Agency for Health Care Policy and Research evidence-based smoking cessation clinical guidelines have clearly endorsed the concept of hospital-based smoking intervention. The challenge for managed care is to find ways to implement the elements of model intervention programs into existing health care delivery systems. 19 references.
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Office Interventions for Adolescent Smokers Source: Adolescent Medicine: State of the Art Reviews. 11(3):577-588, October 2000. Summary: The authors discuss two types of smoking cessation interventions that physicians can use in their offices with adolescents: (1) behavioral and (2) pharmacologic. Adolescent smoking behavior is influenced by different physiological and psychosocial factors, and this behavior progresses through different stages. Each stage offers an opportunity for different types of intervention. Clinicians should anticipate smoking initiation by adolescents and focus on prevention, considering every office encounter an opportunity for clinician-initiated intervention. They should ask the adolescents specific questions, using a screening smoking history to assess smoking behavior. Following initial assessments, they should provide appropriate levels of behavioral intervention. For motivated teens, pharmacologic interventions can be an important addition to behavior modification. These include nicotine replacement
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therapy (gum, transdermal patch, oral inhaler, and nasal spray) and nonnicotine replacement therapy (bupropion). Profound biochemical and physiological effects compounded by the influence of psychosocial and genetic factors make treating adolescent nicotine addiction difficult, and primary failure rates for quitting are high in adolescents. Continuing support from the primary care physician is essential. 2 figures, 6 tables, 63 references. •
Effectiveness of Interventions to Help People Stop Smoking: Findings From the Cochrane Library Source: British Medical Journal. 321(7257):355-358, August 5, 2000. Summary: Researchers summarize evidence of the effectiveness of available smoking interventions, based on findings from the Cochrane Tobacco Addiction Review group. The group identifies and summarizes evidence of interventions to reduce and prevent tobacco use, creating and maintaining systematic reviews to inform clinicians, policymakers, and people who want to quit smoking. Summary points include: (1) advice given by doctors, structured interventions by nurses, and individual and group counseling are effective forms of intervention; (2) generic self-help materials are no more useful than brief advice but more effective than doing nothing, and personalized materials are more effective than are standard materials; (3) anxiolytics and lobeline are ineffective; (4) all forms of nicotine replacement therapy are effective; (5) the antidepressants nortriptyline and bupropion increase cessation rates in a small number of trials, although the usefulness of the antihypertensive drug clonidine is limited by side effects; and (6) the effectiveness of aversion therapy, acupuncture, mecamylamine, hypnotherapy, and exercise is uncertain. 27 references.
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Promoting Cessation of Tobacco Use Source: Physician and Sportsmedicine. 28(12):59-60, December 2000. Summary: Tobacco causes over 450,000 deaths yearly, and although adults smoking rates have decreased in the past 2 decades, the decline has leveled off recently, and youth tobacco use is increasing. The recently released Public Health Service Clinical Practice Guideline, entitled Treating Tobacco Use and Dependence, contains evidencebased information about behavioral counseling; first-line pharmacologic therapies (e.g., nicotine-delivered agents and sustained release bupropion hydrochloride); and secondline pharmacologic therapies (e.g., clonidine hydrochloride and nortriptyline hydrochloride). Since most tobacco users see health care professionals each year, a first step to effective care is systematic institutional identification and tracking of these people. Tobacco dependence should be considered a chronic disease. Effective treatments are available, and clinicians should treat their patients through periods of relapse and remission. Every patient who uses tobacco should be offered an effective treatment. Even brief consultation at every clinic visit is a significant step toward improving abstinence rates. The guide offers various brief interventions for treating patients according to their smoking status. Relapse prevention counseling is important and should include congratulations for success, encouragement of patient problem solving, and identification of specific problems that threaten abstinence. 4 references.
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Smoking Cessation Guidelines for Health Professionals: An Update Source: Thorax. 55(12):987-999, 2000. Summary: The authors update the evidence base and key recommendations of the Health Education Authority smoking cessation guidelines for health professionals
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published in 1998. This update used current Cochrane reviews as well as individual studies. It presents additional detail about the effectiveness of interventions and comments on issues related to implementation. Recommendations include clarification of important ideas addressed only in general terms in the original guidelines. This update concludes that smoking cessation interventions delivered via the National Health Service are a very cost-effective method of preserving life and reducing ill health. The strategy that the guidelines recommend involves the following: (1) General practitioners should opportunistically advise smokers to quit during routine consultations, giving advice on and/or prescribing effective medications to help them and referring them to specialist cessation services; (2) specialist smokers' services providing behavioral support for smokers who want help stopping, as well as effective medications, should be provided; (3) specialist cessation counselors should provide behavior support for people in hospitals and pregnant smokers who want to quit; and (4) all health professionals involved in smoking cessation should encourage and assist smokers in the use of nicotine replacement therapies or bupropion. The key recommendations of the 1998 guidelines are reinforced. New key features of this update include (1) clarification of what primary health care teams can be expected to undertake, (2) the recommendation that smokers be referred to specialist smokers' clinics, (3) a key distinction between behavioral support provided by trained smoking cessation specialists and more limited support provided by other health professionals as part of routine care, (4) recommendations concerning bupropion, and (5) the recommendation that hospitals be smoke-free and this policy be strictly enforced. 1 table, 70 references. •
Smoking Cessation in Primary Care Source: Indiana Medicine. 89(2):165-168, March-April 1996. Summary: A smoking cessation specialist outlines three areas in which health care professionals can play an important role: (1) The medical setting, (2) office-based interventions, and (3) pharmacologic therapy. With regard to the medical setting, health care professionals should ensure that offices and hospitals are smoke-free, reduce the exposure of their patients to the advertising and promotion of tobacco products by subscribing to magazines that do not contain any tobacco advertising, and not focus their attention on abstinence as the only outcome. Although abstinence is the ultimate goal, movement through the stages of change; i.e., precontemplation, contemplation, preparation, action, and maintenance, is an important outcome in itself. Persons in the preparation stage of readiness are twice as likely to stop smoking on the next attempt compared to those who are in the contemplation stage at the time of the initial intervention. The National Cancer Institute has developed an office-based intervention for physicians and other health professionals that provides brief but effective intervention. It is based on the four A's: (1) Ask all patients about their smoking behavior, (2) advise every smoker to stop smoking, (3) assist every smoker in setting a quit date, and (4) arrange a followup visit. Pharmacological therapy offers a useful adjunct to smokers who are trying to stop smoking. Although nicotine gum has recently been overshadowed by the introduction of nicotine patches, it still has a role to play in smoking cessation and is effective when used properly. After initiating nicotine patch therapy on the stop date, the patient should have a followup physician visit within the first 2 weeks. For those who have not stopped smoking at 4 weeks while using the patch, the author recommends that the patch be discontinued and the patient encouraged to establish a new quit date in the near future. Patients with a high degree of nicotine dependence may need a more intensive program such as a group intervention or an inpatient treatment program where patients are hospitalized to initiate abstinence. Pharmacologic agents under investigation include nicotine nasal
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spray and bupropion. The author concludes by saying that the physician plays a key role in helping patients stop smoking. 20 references. •
Should the Use of Smoking Cessation Products Be Promoted by Dental Offices?: An Evidence-Based Report Source: Journal of the Canadian Dental Association. 67(3): 149. March 2001. Contact: Available from Canadian Dental Association. 1815 Alta Vista Drive, Ottowa, ON K1G 3Y6. (613) 523-1770. E-mail:
[email protected]. Website: www.cda-adc.ca. Summary: This article reports on a study undertaken to address the issue of whether dentists should promote the use of smoking cessation products. In the study, an evidence based methodology was applied to find answers to three questions: Does tobacco use affect periodontal health? Are dentists effective cessation counselors? Do smoking cessation products improve the effectiveness of cessation intervention? The author searched MEDLINE and undertook manual searches, uncovering relevant evidence to use in developing evidence based recommendations. There is fair evidence that tobacco use is a major factor in the progression and treatment outcome of adult periodontitis and that quitting tobacco use is beneficial to periodontal health. There is good evidence to recommend that oral health professionals provide cessation counseling. Quit rates are nearly doubled when cessation services are offered. There is good evidence to recommend the use of smoking cessation adjuncts, including transdermal nicotine and nicotine gum, as well as bupropion (an antidepressive drug that has shown some effectiveness in smoking cessation). The author concludes that in view of the strong supporting evidence, dental offices should incorporate systematic smoking cessation services into routine patient care and should promote the use of proven cessation products by patients who are attempting to quit. 2 tables. 54 references.
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Treatment of Nicotine Addiction Source: Texas Dental Journal. 117(6): 26-32. June 2000. Contact: Available from Texas Dental Association. 1946 South Interregional Highway, Austin, TX 78704-3698. (512) 443-3675. Website: www.tda.org. Summary: This article outlines strategies for dentists to use when helping patients address a nicotine addiction. The authors note that people begin using tobacco for sociocultural reasons, but the social stimuli are quickly surpassed in influence by internal drug seeking and drug using behavior. Cessation strategies that stress only behavioral interventions and do not deal with the patient's physical nicotine dependence address only part of the problem. The authors note that a systematic and caring approach that includes education, behavioral counseling, and psychological support together with pharmacotherapy results in significantly higher abstinence rates. The authors review various cessation strategies, including the Four A's (Ask, Advise, Assist, Arrange), drug therapies, nicotine gum, transdermal nicotine patches, nicotine nasal spray, nicotine inhalation system, bupropion HCl (Zyban), weight control programs, and diet therapy. The authors conclude that the combination of pharmacotherapy and behavioral interventions, even on a minimal level, have been shown to be effective in cessation. Such strategies are certainly highly cost effective, given the enormous costs to society of smoking related illnesses. One chart summarizes the FDA approved aids used in nicotine cessation. 2 figures. 23 references.
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Pharmacotherapy of Smoking Cessation Source: Archives of Family Medicine. 9(3):270-281, March 2000. Summary: The authors reviewed data on the efficacy of approved medications, benefits, adverse effects, and appropriate use of these products in smoking cessation. They also discuss nicotine addiction and treatment for special populations. Most smokers want to quit, but their quit attempts are usually unsuccessful because of their addiction to nicotine. The Agency for Health Care Policy and Research (AHCPR) published its Smoking Cessation Clinical Practice Guideline recommending a 5-step approach to be used by primary care physicians: (1) Ask, (2) advise, (3) assess, (4) assist, and (5) arrange. Pharmacological treatment for smoking cessation includes (1) nicotine replacement therapy (NRT), including nicotine polacrilex gum, transdermal nicotine patches, nicotine nasal sprays, and nicotine inhalers; (2) nonnicotine drugs, including bupropion, an aminoketone with doperminergic and adrenergic actions; and (3) combination drug therapy, including combined use of NRT products and combined use of the transdermal patch and bupropion. The AHCPR recommends that clinicians offer minorities the same smoking cessation treatments proven to be effective for the general population. Behavioral therapy has been shown to be effective and should be encouraged for helping pregnant women quit smoking. If this is not effective, NRT methods should be considered since they deliver lower levels of nicotine than smoking. Physicians should adopt a more aggressive approach to encouraging smoking cessation among patients with cardiovascular and lung disease, including combination drug therapy since these patients are likely to be more nicotine dependent. Physicians should be aware that relapse is common among smokers during and after smoking cessation treatment. The authors concluded that recent increases in approved pharmacological options for smoking cessation provides primary care physicians with a wide range of treatment approaches. 1 figure, 3 tables, 96 references.
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Smoking and Women's Health Source: International Journal of Gynecology and Obstetrics. 70(1):159-163, July 2000. Summary: The author discusses the role of the obstetrician/gynecologist in reducing morbidity and mortality from cigarette smoking by (1) educating women about the dangers, (2) advising them not to smoke, and (3) assisting those who do smoke to quit. Education is needed regarding both the reproductive and non-reproductive health issues of tobacco use. Smoking among women is associated with an increased risk of cancer, coronary artery disease, bronchitis, emphysema, peripheral vascular disease, cerebrovascular disease, and gastric ulcers. Smoking also affects many aspects of reproductive health, including fertility, menstrual function, and contraceptive options. In the United States, the National Cancer Institute recommended a program of clinical interventions (four A's), and has encouraged all physicians and other health care professionals to incorporate them into their practices with the goal of reducing the number of smokers. The four A's are (1) ask all patients if they smoke, (2) advise those who do smoke to stop, (3) assist smokers in their efforts to quit, and (4) arrange followup to review the patient's progress. There is evidence from clinical trials that the use of nicotine replacement or bupropion will improve smoking cessation rates. There are also nicotine gums, transdermal patches, inhalers, and nasal sprays available. There is some evidence that using both bupropion and the nicotine patch may be even more effective than using either agent alone. 12 references.
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Smoking and Women's Health: Opportunities to Reduce the Burden of Smoking During Pregnancy Source: Canadian Medical Association Journal. 163(3):288-289, August 8, 2000. Summary: The authors discuss the role of clinicians in smoking cessation in pregnant women. The need to assess the smoking habits of each woman during each contact with a clinician is clear. Clinicians who provide health care to women have an important role to play in reducing the burden of smoking among women. Studies indicate that brief cessation counseling for 5 to 15 minutes when delivered by a trained provider with pregnancy-specific self-help materials significantly increase rates of cessation among pregnant smokers. Five specific steps toward cessation (Ask, Advise, Assess, Assist, and Arrange) and recommended providers are outlined in a one-page form, Brief Smoking Cessation Counseling for Pregnant Patients. Efforts to prevent tobacco exposure should begin before conception since more than 50 percent of women do not recognize that they are pregnant until after the fourth week of gestation. Pregnant women who smoke most heavily do not appear to respond to behavioral interventions. The use of pharmacologic approaches to achieve smoking cessation in women who are unable to stop smoking, including nicotine replacement therapy, nonnicotine products, such as bupropion hydrochloride, and second-line pharmacotherapies, such as clonidine and nortriptyline, has been suggested; but the safety of these approaches during pregnancy is not well documented. Long-term reduction in tobacco exposure during pregnancy can be achieved only by encouraging teenage girls and young women not to start smoking. 10 references.
Federally Funded Research on Bupropion The U.S. Government supports a variety of research studies relating to bupropion. 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 bupropion. 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 bupropion. The following is typical of the type of information found when searching the CRISP database for bupropion: •
Project Title: A CLINICAL TRIAL OF TWO MEDICATIONS ON SMOKING CESSATION Principal Investigator & Institution: Johnson, Karen C.; Associate Professor of Medicine; Preventive Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163
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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Timing: Fiscal Year 2002; Project Start 07-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Cigarette smoking poses a serious but preventable health risk. Even though the detrimental effects of smoking are well known, the prevalence of cigarette smoking remains high in the U.S., particularly for younger persons, persons of lower socioeconomic status, and minority groups. Although some persons quit smoking on their own or with the help of behavioral smoking cessation interventions, there are a substantial number of smokers who are unable to quit smoking or relapse to smoking without the aid of pharmacologic therapy for smoking cessation. Currently, there are two types of pharmacologic therapies (Nicotine Replacement Therapy and Sustained-release bupropion) that are FDA approved for smoking cessation in the U.S. To date, there has been no clinical trial comparing use of the nicotine patch and sustained-release bupropion, alone or in combination, as pharmacologic therapy for smoking cessation among low income, younger participants or in minority participants. Given the high relapse rates among these groups in general, the combination of nicotine replacement therapy and sustained-release bupropion may be particularly efficacious. Therefore, we hypothesize that use of a combination of the nicotine patch and sustained-release bupropion as compared to use of the nicotine patch alone or to sustained-release bupropion alone will result in increased initial and long term rates of smoking cessation in younger low income and minority persons who smoke. We plan to test these hypotheses in this double blind clinical trial by randomizing younger, low income and minority persons who smoke to one of three groups: Group 1) Nicotine patch plus placebo sustained-release bupropion, Group 2) Sustained-release bupropion plus placebo nicotine patch, or Group 3) Nicotine patch plus sustained-release bupropion. Our primary endpoint assessment is smoking cessation rates by self-report verified by biochemical validation at different time points between the three treatment groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIDEPRESSANT TREATMENT FOR DEPRESSED COCAINE DEPENDENT PATIENTS Principal Investigator & Institution: Oliveto, Alison H.; Research Scientist; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: Preliminary data with two antidepressants, bupropion and sertraline, suggest a common mechanism for treating cocaine dependent patients, particularly those with concurrent depression. In addition to other mechanisms of action, these two share dopamine reuptake inhibition which may be important, not only due to the important role that dopamine plays in cocaine induced reinforcement, but also because the doparnine reuptake carrier can be upregulated in many cocaine patients. This upregulation may respond to renormalization using a weak blocker of the dopamine transporter when patients are cocaine-free and craving. Thus, the aim of this proposal is to examine the clinical efficacy of bupropion vs. placebo (years I3) as well as sertraline vs. placebo (years 3-5) in currently abstinent, depressed cocaine-dependent volunteers. We will also pilot the use of a pharmacological augmentation strategy for nonresponders to the initial trial with sertraline. Each I2-wk, double blind, randomized clinical trial will provide treatment for 60 depressed cocaine-dependent individuals (1865 yrs). Participants first will be placed in research beds on the Quarterway House at the VA CT Healthcare System to initiate initial cocaine abstinence. Subjects will be randomly assigned to receive either active medication (i.e., 300 mg/day of bupropion in study I and 200 mg/day of sertraline in study 2) or placebo. At the end of week 2,
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depressive symptoms severity will be redetermined and used as a stratifying factor in subsequent analyses. Then participants transfer to the Outpatient Treatment Research Program, where they continue to receive active medication or placebo and participate in weekly individual cognitive behavioral therapy for weeks 3-12. During weeks 3-12, participants can earn monetary incentives for attending scheduled visits and returning take-home medication bottles. During the pharmacological augmentation portion of the sertraline trial, nonresponders continue to receive the placebo or sertraline under blinded conditions and openly receive bupropion (50 mg/day) as they continue to participate in cognitive behavioral therapy during weeks 13-16. Efficacy will be determined by length of time in treatment, length of time to relapse by self-report and urine toxicology, depressive symptom severity and psychosocial functioning. Depressive symptom severity as a prognostic factor in treatment response will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASSESSING AND UNDERSTANDING TOBACCO DEPENDENCE Principal Investigator & Institution: Fiore, Michael C.; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: (Applicant's Description) Why is relapse far and away the most likely outcome of a cessation attempt? It is difficult to imagine answers to this question that do not implicate tobacco dependence. Dependence is the conceptual nexus integrating the surface features of addiction (e.g., heavy use, severe withdrawal, tendency to relapse, etc.). Greater understanding of the construct linking those phenomena should foster more rapid progress in developing effective treatments. The overarching goal of this research is to develop improved dependence- assessment instruments through theoretical scale construction that focuses on hypothesized mechanisms underlying dependence, rather than on surface manifestations (e.g., cigarettes per day, whether one inhales). Once initial scales are constructed, they will be subjected to diverse validity assessments. Two studies are proposed. In Study I, 460 smokers will be recruited such that they reflect a broad range of dependence. All will participate in a cessation trial with random assignment to 2 or 4 mg nicotine gum or placebo. Three theory-based constructs will serve as chief criteria for the selection of Subscale on the Dependence Questionnaire (DQ): withdrawal severity, pre-cessation smoking heaviness, and relapse. These will be assessed with multiple, sensitive indices. For example, assessments of withdrawal will include measures of both symptom elevation and symptom trajectory. Moreover, over the first five days of cessation, intensive assessment of symptoms will occur via computerized telephone interview. Two additional measures will be gathered because of their strong motivational links to dependence. Genetic markers related to dopaminergic structures and activities will be assessed in all 460 subjects. In addition, a subsample of placebo subjects (N=60) will participate in a behavioral economic assessment, allowing examination of elasticity as a dependence index and providing a further criterion against which to test the DQ. Study 2 (N=400) will employ the same design with two exceptions. First, the study will not involve the elasticity assessment. Second, the active smoking cessation pharmacotherapy will be changed to bupropion so that the stability of the factor structure and predictive validity of the DQ can be determined in a systematic replication. The validity data will address both vital clinical as well as theoretically significant criteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOBEHAVIORAL LUNG CANCER PREVENTION PROGRAM Principal Investigator & Institution: Lerman, Caryn E.; Professor of Psychology in Psychiatry; V T Lombardi Cancer Res Center; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001; Project Start 10-SEP-1993; Project End 30-JUN-2001 Summary: ABSTRACT=In our original grant (R01CA63562), we evaluated the impact of a smoking cessation treatment which incorporated motivational feedback about genetic susceptibility to lung cancer. We found strong positive effects of genetic feedback on perceived risk, perceived quitting benefits, and fear arousal. While smokers receiving genetic feedback made more quit attempts, they were no more likely to quit than were smokers receiving standard minimal contact cessation treatment. Observing that the vast majority of smokers were unable to quit, even in the face of perceived vulnerability and heightened motivation, we became interested in the genetic basis of nicotine dependence and smoking cessation. The strongest evidence (by our group and others) supports the role of the dopamine transporter gene (SLC6A3) which regulates reuptake of dopamine at the synapse. This is consistent with a large body of data suggesting that the reinforcing effects of nicotine are due to its impact on the neurotransmitter dopamine. Thus, in this competitive renewal, we propose to extend our research by evaluating the role of SLC6A3 in the response of smokers to pharmacological smoking cessation treatment (bupropion/Zyban). We have selected bupropion because: (a) initial data from randomized clinical trials provide strong support for its efficacy as a smoking cessation treatment, and (b) bupropion has inhibitory effects of dopamine transport (the protein product of the SLC6A3 gene). The specific aims of the proposed research are: (1) to evaluate the role of genetic factors in response to standard smoking cessation treatment; (2) to evaluate the role of genetic factors in response to bupropion treatment; and (3) to evaluate the psychobiological mechanisms by which genotype and bupropion influence smoking cessation. The study will be a double blind randomized placebocontrolled clinical trial of bupropion in 600 adult male and female smokers. The factorial design includes one treatment factor (bupropion plus standard treatment (with nicotine patch) vs. placebo plus standard treatment with patch) and one subject factor (SLC6A3 genotype, genetically predisposed vs. genetically protected). Bupropion or placebo will be delivered over a 10-week treatment period. All subjects will receive standard minimal contact cessation treatment, which includes two in-person sessions plus five brief structured phone-counseling sessions. A major innovation of this study is that we will use a behavioral economics computer paradigm to evaluate the reinforcing value of nicotine at pre-treatment and during bupropion therapy. Other mediating outcomes (mood, withdrawal) will be assessed at pre-treatment and at multiple points during treatment. The primary smoking cessation outcomes will be assessed at 1-, 6and 12- months post-treatment. The proposed research will be the first to examine the role of specific genetic factors in response to pharmacological therapy for smoking cessation and to evaluate novel mediating mechanisms. The long-term objective is to provide information necessary to match smoking cessation treatments to individuals, based on their genetic predispositions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BODY IMAGE TREATMENT FOR WEIGHT CONCERNED SMOKERS Principal Investigator & Institution: Clark, Matthew M.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003
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Summary: (provided by applicant): This application will serve as the foundation on which the Principal Investigator will build a major line of research dedicated to the area of improving smoking abstinence rates in weight-concerned smokers. Many individuals smoke to manage their weight. This subpopulation of smokers has been classified as having weight concerns. Weight concerned smokers have lower smoking abstinence rates compared to non-weight concerned smokers, and women have higher rates of weight concern than men. Behavioral weight management interventions added to nicotine dependence treatment have not been found to be effective and pharmacological interventions have delayed rather than prevented weight gain. New avenues need to be explored for this difficult-to-treat subpopulation. A novel approach is to focus on changing the weight concerns themselves by implementing a body image intervention. Negative body image has been found to predict reduced rates of smoking abstinence. The primary aim of this study is to evaluate the efficacy of body image treatment compared to weight management intervention on improving the smoking abstinence rates in weight concerned smokers after 12 weeks of treatment and at 6-month (week 24) follow-up. A further aim is to examine the effect of body image treatment on improving body image satisfaction, and reducing weight concerns in weight concerned smokers. We hypothesize that the body image treatment will be associated with higher 7-day point-prevalence smoking abstinence rates, greater improvements in body image satisfaction scores, and decreased weight concerns at end of treatment (week 12) and at 6-month follow-up as compared to the weight management intervention. The ultimate goal is to develop effective interventions that will reduce tobacco-related morbidity and mortality in this population. This is consistent with the objectives of the National Cancer Institute to develop and test new behavioral, pharmacological, and combination therapies to treat nicotine dependence, with special emphasis on populations at high risk. Subjects will be randomly assigned to either a 12-week group cognitive-behavioral treatment for body image improvement (experimental group) (N=20) or to a 12-week group behavioral weight management treatment (contact control group) (N=20). Subjects in both conditions will receive bupropion and prescription for home-based exercise. The major assessments will occur at end-of-treatment (week 12) and at 6-month (week 24) follow-up. Dependent measures include 7-day point prevalence smoking abstinence confirmed with expired air carbon monoxide, and self-report measures of body image satisfaction and weight concerns. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION AND BEHAVIORAL TREATMENT FOR YOUNGER SMOKERS Principal Investigator & Institution: Hurt, Richard D.; Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-MAY-2004 Summary: (adapted from investigator's abstract): The primary aims of this study are: (1) to evaluate the efficacy of a 12-week course of sustained release buproprion (300mg/d) compared to placebo on end of treatment and 1-year abstinence rates, (2) to evaluate the efficacy of brief office intervention with parental support compared to minimal intervention on the end of treatment and 1-year abstinence rates, and (3) to determine if the combination of buproprion with brief office intervention with parental support is more effective than placebo and minimal intervention. The primary hypotheses to be tested are: (1) a 12-week course of buproprion will increase the end of treatment and 1year smoking abstinence rates, compared to placebo, and (2) smoking abstinence rates at the end of treatment and 1-year will be increased with brief office intervention with
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parental support, compared to minimal intervention. The ultimate goal of this work is to develop effective interventions, which will reduce the risk of tobacco-related morbidity and mortality in these younger smokers. The investigator proposes to test these hypotheses and accomplish these aims by providing 616 adolescent cigarette smokers aged 13-17 with buproprion or placebo for 12 weeks combined with minimal intervention or brief office intervention with parental support, in a 4-group, randomized double blind design. The four groups will be: (1) placebo buproprion, minimal intervention, (2) placebo buproprion, brief office intervention with parental support, (3) active buproprion, minimal intervention, and (4) active buproprion, brief office intervention with parental support. Primary assessments will be point prevalence smoking abstinence rates at end of treatment (week 12) and at 52 weeks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CESSATION
BUPROPION
AND
WEIGHT
CONTROL
FOR
SMOKING
Principal Investigator & Institution: Marcus, Marsha D.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-JUL-1986; Project End 30-NOV-2004 Summary: Although rates of smoking have declined, the decrease in prevalence has been much less pronounced in women than in men, and women are particularly vulnerable to ongoing smoking-related morbidity and mortality. One reason for gender differences in smoking cessation is concern about cessation-related weight gain among women. In the previous grant period, we tested the efficacy of two adjuncts to a standard cessation program for weight concerned women, behavioral weight control (WEIGHT) and cognitive behavior therapy to reduce weight concerns (CBT). Results of this trial have shown that CBT is a promising adjunctive treatment for weight concerned women. Specifically, 59.7% of known in the CBT condition were abstinent from smoking in post- treatment. Further, CBT yielded significantly higher abstinence rates in 3month follow-up when compared to standard cessation only or the WEIGHT adjunct, with cessation rates of 39.4%, 23.6%, and 22.6% for the three groups, respectively. Nevertheless, abstinence rates decreased significantly during follow-up for all groups, and in the present study, we propose a randomized, double-blind, controlled trial to determine whether the addition of buproprion (Zyban) to CBT treatment for weightconcerned women will enhance longer-term abstinence. Four hundred fifty weightconcerned women smokers will be randomized to either cognitive behavioral treatment for weight concerns plus standard cessation (CBT) or standard smoking cessation only (STANDARD), and six months of either buproprion (Zyban) or placebo. Primary outcome will be rates of smoking abstinence and time to relapse across the four treatment conditions. In addition, we will determine the effects of these treatments on tobacco withdrawal, mood, and weight. Results of this investigation will provide information on the relative efficacy of CBT and buproprion alone and in combination, and the utility of drug and counseling strategies that are specifically tailored for a highrisk population. This is a competing continuation of 2-R01-DA04174-13. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION AS A SMOKING CESSATION AID IN ALCOHOLICS Principal Investigator & Institution: Grant, Kathleen M.; U.S. Dept/Vets Affairs Med Ctr(Omaha) Affairs Medical Center Omaha, NE 68105 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004
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Summary: (provided by applicant): Objectives: The purpose of the current proposal is to test the use of sustained release bupropion in patients in treatment for alcohol abuse/dependence as an aid for smoking cessation. It is our overall hypothesis that cigarette smoking cessation can be achieved in patients during treatment for alcohol abuse/addiction, particularly if treatment is tailored. Our proposed work will address the following four specific aims: Aim one will assess whether the use of sustained release bupropion as a smoking cessation alters abstinence from cigarette smoking for patients with alcohol abuse/dependence in an alcohol treatment program. Aim two will assess whether the use of sustained release bupropion as a smoking cessation aid alters sobriety from alcohol in patients. Aim three will assess the incidence of side effects of sustained release bupropion when used as a smoking cessation aid for patients with alcohol abuse or dependence in an alcohol treatment program. Aim four will assess the adherence to the medication regimen between the two groups. Research Design and Methodology: We propose to use a randomized, double blind, placebo controlled clinical trial to test the safety and efficacy of the addition of a nine-week course of sustained release bupropion for cigarette smoking cessation in a VA SATC and a community-based alcohol treatment program. 200 total patients will be enrolled. Patients meeting study criteria will be randomized to receive either sustained released bupropion or placebo. Both groups will receive nicotine replacement therapy. Participants will be followed for 6 months. A repeated measure design will be used to compare outcome measures of smoking cessation and sobriety from alcohol in two groups (control, intervention) at baseline, 4 weeks, 9 weeks, and 6 months. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION AS AN ADJUNCT TO THE NICOTINE PATCH PLUS CBT Principal Investigator & Institution: Fava, Maurizio; Director, Depression Clinical & Res. Pro; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: We are proposing a five-year, double-blind, placebo-controlled trial on the smoking cessation efficacy of bupropion as an adjunct to the standard combination of group cognitive-behavioral therapy (CBT) plus nicotine replacement. Our primary aims are 1) to examine the additional benefit of adding the antidepressant bupropion to a standard treatment for smoking cessation of CBT and nicotine replacement among smokers who have a history of either current or past unipolar depressive disorders (major depressive disorder, dysthymia, and minor depression), and 2) to determine, if bupropion indeed improves in this population a smoker's odds of quitting, whether its effect is achieved mainly through its impact on the negative mood states associated with depression. In order to provide a powerful test of both hypotheses, this study will enroll only smokers with a history of either current or past unipolar depressive disorders. In addition, allowing the inclusion of patients with a history of unipolar depressive disorders makes the proposed study more clinically relevant and its findings more generalizable, as several studies suggest that, as the prevalence of smoking continues to diminish in the general population, an increasing percentage of those who remain smokers are patients with psychiatric illnesses, especially depression. We expect that the efficacy of the standard combination of group CBT plus nicotine replacement will be greatly enhanced by the addition of bupropion in all smokers, but that the addition of bupropion will be especially helpful to those smokers who currently suffer from clinically significant depressive symptoms. The study involves the enrollment over 48 months of 300 individuals. We predict that 50 percent of the enrolled patients will meet
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criteria for current unipolar depressive disorders. After the 12-week acute treatment phase, patients will be followed for 12 months. The study design therefore involves the random assignment of current or past history of unipolar depressed patients to two treatment conditions: 1) group CBT plus nicotine patch plus bupropion (current depressive disorder bupropion group, estimated n=75; past depressive disorder bupropion group, estimated n=75); 2) group CBT plus nicotine patch plus placebo (current depressive disorder placebo group, estimated n=75; past depressive disorder placebo group, estimated n=75). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION FOR HOSPITALIZED SMOKERS W CORONARY DISEASE Principal Investigator & Institution: Rigotti, Nancy A.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 20-MAR-1999; Project End 28-FEB-2003 Summary: Over 2 million Americans are hospitalized annually with a myocardial infarction (MI) or unstable angina pectoris, two acute, potentially fatal manifestations of coronary heart disease (CHD) that are responsible for substantial morbidity, mortality, and health care costs. Smoking cessation is highly cost-effective and universally recommended for the approximately 20 percent of these patients who smoke. Hospitalization for acute CHD is an excellent time to initiate smoking cessation because it requires temporary tobacco abstinence at the same time that illness increases smokers' motivation to quit. However, at least 40 percent of smokers fail to quit even with the most effective current treatment, cognitive-behavioral counseling that begins in the hospital and continues after discharge. More powerful intervention strategies are clearly needed. Adding pharmacotherapy to counseling, which is standard practice in outpatients, is a new approach that has not been tested in this setting. Concern about the safety of nicotine replacement in MI patients limits its use. A non-nicotine antidepressant, sustained-release (SR) bupropion (Zyban, Wellbutrin SR), has demonstrated efficacy for smoking cessation and was recently FDA- approved for this use. Bupropion appears to be safe in cardiac patients and may have the additional benefit of preventing post-MI depression, an independent predictor of mortality. We propose to test the efficacy and safety of this novel treatment, bupropion SR, for smoking cessation in adult smokers hospitalized with acute CHD. We have designed a randomized, double-blind, placebo-controlled trial to determine whether bupropion SR, initiated in the hospital and continued for 12 weeks, is effective and safe when added to a previously-tested nurse-delivered cognitive-behavioral smoking counseling intervention that begins in the hospital and continues by telephone contact after discharge. Outcomes will be assessed at hospital discharge and 1, 3, and 12 months after the start of treatment. The primary outcome measure is biochemically-confirmed 7-day point prevalence tobacco abstinence at 1 year follow-up. Secondary objectives are to test whether bupropion SR delays the time to smoking relapse; increases the smoking cessation rate at the end of treatment (3-months); and reduces CHD morbidity and depressive symptoms and improves health-related quality of life over 1 year. If found to be safe and effective, bupropion SR could become a standard part of "secondary prevention" therapy for smokers with acute CHD, a large, high-risk, high-cost patient group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION FOR SMOKING CESSATION IN PREGNANCY Principal Investigator & Institution: Miller, Hugh S.; Obstetrics and Gynecology; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Smoking in pregnancy is associated with a variety of complications, including low birth weight (LBW), intrauterine growth restriction (IUGR), antenatal bleeding and pre-term birth (PTB). These significant health hazards could largely be prevented with successful antepartum smoking cessation. In recognizing both the success and the limitations of counseling based smoking cessation programs, we are interested in piloting the use of pharmacologic agents for reduced smoking during pregnancy. The first objective of the proposed research is to evaluate the efficacy of a pharmacologic aid for successful smoking cessation in pregnancy. The specific aims include evaluating bupropion SR's efficacy for both cessation and reduction of antenatal smoking by comparing pregnant women receiving smoking cessation counseling combined with placebo to those pregnant women who receive smoking cessation counseling combined with bupropion SR. The second objective of the proposed research is to evaluate the safety of bupropion SR used for smoking cessation in pregnancy. The specific aims include determining the adverse events and adverse effects associated with antenatal bupropion administration. Secondarily, the pilot seeks to evaluate the impact of bupropion SR on maternal well being, anxiety, depression, psychosocial variables and neonatal outcome (birth weight, Apgar scores, and neonatal intensive care unit admission rate). This research will consist of a pilot double blind placebo controlled randomized trial in which pregnant women who self-report continued smoking at the inception of prenatal care, will be randomized to one of two groups. The interventions will consist of brief smoking cessation counseling in combination with either placebo or bupropion SR. Participants will be surveyed to determine important demographic factors, psychosocial variables, and intercurrent medical illnesses, including measures of psychiatric disease, particularly concurrent depression. Maternal outcome measures will include cessation and smoking reduction rates by self-report and biochemical analysis (urinary cotinine and breath carbon monoxide analysis). The proposed research seeks to evaluate whether a pharmacologic aid (bupropion SR) administered antenatally can achieve higher rates of smoking cessation and smoking reduction without imposing serious adverse outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION IN ADOLESCENTS WITH COMORBID ADHD & DEPRESSION Principal Investigator & Institution: Daviss, William B.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 06-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Attention deficit hyperactivity disorders (ADHD) in youth occur comorbidly with other psychiatric conditions approximately two thirds of the time. Major depressive disorder and dysthymic depression are common, occurring in as many as 40% of youth with ADHD. The comorbid occurrence of ADHD and depression (ADHD + Dep) may cause substantial long-term morbidity. While psychopharmacology is widely used to treat juvenile ADHD and/or depression, no research has established an efficacious treatment for ADHD + Dep, or for most other comorbid ADHD disorders. This five year Mentored Patient-Oriented Research Career Development Award (RCDA) will provide the candidate, a board certified child and
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adolescent psychiatrist, training to undertake pharmacological trials of youth with ADHD and comorbid disorders. The candidate has had extensive previous clinical experience and some research experience in the pharmacological treatment of juvenile ADHD + Dep. The RCDA will provide the candidate formal training in pharmacology, clinical trial design, and statistical analyses as well as the empirical assessment of juvenile ADHD, depression, and other comorbid psychopathology. The candidate will also receive training in ethical issues germane to juvenile psychopharmacology studies. Training will occur through a combination of formal coursework, guided readings, and consultation with mentors having relevant expertise. This training will be applied in a pharmacologic study of adolescents with ADHD and depression (major depression, dysthymia). The protocol will consist of a 2-week washout/observational period, then an 8-week randomized, placebo-controlled trial (RCT) to determine the efficacy of bupropion SR. Then a 24-week open label continuation phase will be used to determine if treatment response and tolerability persist. Exploratory analyses will assess correlations of initial treatment response with both pharmacological variables (plasma levels of bupropion and its metabolites; noradrenergic and dopaminergic effects as estimated by reuptake blockade of rat synaptosomes) and psychosocial variables (baseline psychopathology and psychosocial impairment). The candidate' s training and research experiences during the RCDA will enable him to pursue larger, more scientifically rigorous pharmacologic trials of youth with ADHD and depressive or other comorbid psychopathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION SR IN ATYPICAL DEPRESSION Principal Investigator & Institution: Golden, Robert; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION SR ON SLEEP Principal Investigator & Institution: Poland, Russell E.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, CA 90502 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION TO PREVENT POSTPARTUM SMOKING RELAPSE Principal Investigator & Institution: Dalton, Madeline A.; Assistant Professor; Pediatrics; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2005 Summary: (provided by applicant) In this R21 grant application we propose to conduct pilot work that will lay the foundation for a randomized clinical trial of bupropion SR to prevent smoking relapse in postpartum women. Although many women quit smoking during pregnancy, up to 70 percent are smoking again within one year of delivery. Behavioral interventions designed to prevent relapse following delivery have met with only limited success. At the same time, several trials have demonstrated that bupropion SR is safe and effective in promoting cessation. However, there are no
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Bupropion
published studies evaluating the effectiveness of bupropion SR in preventing relapse during particularly vulnerable periods, such as the postpartum period. Our ultimate goal is to evaluate the effectiveness of bupropion SR in preventing relapse during the postpartum period among women who quit smoking during pregnancy and are abstinent at the time of delivery through a double-blind, placebo-controlled, randomized clinical trial. This pilot study will allow us to develop and fine tune the methodology for the trial and demonstrate our ability to enroll and follow participants. In this study, we will enroll 50 women at the time of delivery and randomly assign them to receive placebo or bupropion SR for 12 weeks. Our objectives are to: a) test protocols for recruitment, sample collection, and follow-up; b) develop survey instruments; c) evaluate patient compliance; and d) estimate eligibility, participation, and retention rates for the larger trial. Patients and investigators will be blind to treatment assignment. Subjects in the treatment group will receive 300mg bupropion SR (150mg QD am for 7 days followed by 150mg BID for 11 weeks). Subjects in the control group will receive placebo following the same schedule. Both groups will receive 5 telephone-counseling sessions to encourage the maintenance of cessation in accordance with clinical practice guidelines. Patient compliance will be measured using the MEMS Track CapTM (Aprex Corporation, Union City, CA), which records each time and date the medication bottle is opened. Self-reported smoking status will be validated with a urine cotinine dipstick (<=100ng/ml) at baseline and saliva cotinine (<=30ng/ml) at 12 and 26 weeks postpartum. Data on covariates and mediating factors known to be associated with smoking cessation and relapse will be collected at baseline, week 12 and week 26 through telephone interviews. If proven effective in a follow-up randomized trial, the enrollment and implementation strategies we are testing could be utilized to implement a county or state program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION TREATMENT FOR YOUTH SMOKING CESSATION Principal Investigator & Institution: Muramoto, Myra; Assistant Professor; None; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-JUL-2003 Summary: (Applicant's Description) Tobacco use remains the leading preventable cause of premature death in the U.S., and this public health problem will remain so if advances in the treatment of nicotine dependence do not occur. While the approved medications for smoking cessation to date are those that provide nicotine replacement, recent studies evaluating the effects of novel non-nicotine medications suggest that significant improvements in cessation rates may be possible. One of the most promising non-nicotine medications is bupropion (Zyban). Bupropion has been available as an antidepressant that increases dopamine availability and thus elevates mood, and will be FDA approved as a smoking cessation medication. Furthermore, it has been investigated as a medication for the treatment of attention deficit/hyperactivity disorder in youth. Because the efficacy of bupropion for adult smoking cessation is greater than nicotine replacement, and because the safety of bupropion has been shown in youth, it is the clear choice for investigation as a pharmacologic treatment for youth smoking cessation. Since the optimal dose for smoking cessation has not been assessed in youth, a dose ranging study to evaluate the safety and efficacy of bupropion for smoking cessation in youth is proposed. The proposed study is a randomized, double-blind, placebo-controlled clinical trial designed to assess (1) which bupropion dose, if any, increases abstinence rates over placebo, and (2) which factors, such as medication adherence, nicotine dependence, and motivation to quit, affect treatment outcome.
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There are a number of potential benefits from the proposed study. The results of the proposed study could lead to a better understanding of how to use a pharmacologic treatment for youth smoking cessation. Initiation of tobacco use is largely a sociocultural process, nicotine dependence is a medical condition whose treatment is optimized when the full armamentarium of medical care is provided. The proposed study will follow Agency for Health Care Policy and Research guidelines for smoking cessation, including a medical model approach that combines behavioral and pharmacologic intervention within a health care environment. While many studies have evaluated cessation methods for adults, there remains a dearth of research evaluating methods for enhancing youth smoking cessation. With so little research upon which to expand, the proposed study could lead to important new understandings regarding the process and mechanisms of youth smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GAMBLING
BUPROPION
VS
PLACEBO
TO
TREAT
PATHOLOGICAL
Principal Investigator & Institution: Black, Donald W.; Professor; Psychiatry; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2005 Summary: (provided by applicant): Pathological gambling (PG) has become a major health concern, particularly as gambling opportunities have proliferated. Despite its importance, there are few treatment options with proven efficacy. This application is submitted in response to PAR-99- 134 "Exploratory/Development Grants for MH Intervention/Research" The goal of the project is to conduct a randomized, double-blind comparison of bupropion-SR versus placebo in the treatment of PG. Bupropion will be used because of its reported efficacy in treating attention-deficit hyperactivity disorder (ADHD), and clinical similarities between PG and ADHD. This study will be one of the first of its kind, and has the potential to provide pilot data supporting the efficacy of a novel treatment for PG. We propose to recruit approximately 80 adults with DSM-IV PC during the first two years of the project, and to randomize subjects to bupropion-SR or placebo for a 12-week clinical trial. Subjects will be recruited through physician referral, advertisements in the local media, and by word-of-mouth. Subjects will be screened with the 20-item South Oaks Gambling Screen (SOGS) and the NORC DSM Screen for Gambling Problems (NODS). Those screening positive for PG (SOGS score equal to or >5 and NODS score equal to or >5) will be offered inclusion in the trial provided they meet specified inclusion/exclusion criteria. Baseline assessments will include the Structured Clinical Interview for DSM-IV, the Structured Interview for DSM-IV Personality Disorders, the Yale-Brown Obsessive-Compulsive Scale Modified for PG (YBOCS-PG), the Hollingshead Scale, the NORC Gambling Self-Administered Questionnaire, and the Global Assessment Scale. Baseline assessment will also include a physical examination, an electrocardiogram, urine drug screen, and other screening laboratories. Measures to gauge improvement will include the YBOCS-PG, three Clinical Global Impression scale ratings, a patient self-rated scale, the Hamilton Depression Rating Scale, and the Attention Deficit Hyperactivity Disorder (ADHD) Symptom Checklist. Following a two-week screening period, subjects will be randomized to medication or placebo. The dosage of bupropion-SR will begin at 100 mg twice daily and increased weekly to a total of 400 mg daily. Subjects on placebo will be administered a similar number o tablets. Subjects will be seen at weeks 1, 2, 4, 6, 8, 10, and 12. Adverse events and concomitant medications will be recorded at each visit. We hypothesize that the subjects receiving bupropion will have better symptomatic
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Bupropion
improvement than subjects receiving placebo. Further, we hypothesize that symptoms consistent with attention-deficit disorder will improve in parallel to the reduction in PG behavior. If bupropion is confirmed as an effective treatment, future studies will include larger samples to help test whether specific subgroups will improve preferentially, and comparisons of bupropion with the SSRI fluvoxamine, and naltrexone, an opiate antagonist, both shown to have efficacy in treating PG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION OF NICOTINE RECEPTORS Principal Investigator & Institution: Martin, Billy R.; Louis/Ruth Harris Professor and Chair; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 30-JUN-2006 Summary: Nicotine produces diverse pharmacological effects after acute administration, and we have shown recently that profound dependence occurs after repetitive exposure. Pharmacological evidence, coupled with molecular biology, has revealed multiple neuronal nicotinic receptor subtypes in brain, and the definitive functional role for these receptor subtypes is slowing emerging. In order to continue establishing the functional role of these receptor subtypes, we will continue to pursue our structure-activity relationship studies that are providing intriguing leads for developing more receptor selective agonists and antagonists. Moreover, these probes are providing a means for assessing structural requirements for activation of the receptor. Analogs will be evaluate for receptor selectivity and efficacy using receptor binding, a battery of in vivo pharmacological effects, and in vitro functional assays. The synthetic analogs that we will be examining have sufficient structural diversity to allow redefinition of the pharmacophore for nicotine receptors. In addition to understanding nicotine's acute actions, we propose to investigate the mechanism by which nicotine produces dependence. We recently developed a dependence model using chronic nicotine infusion in mice. This model will allow us to determine which receptor subtypes are involved in dependence. These studies will consist of substituting receptor selective agonists for nicotine as well as participating withdrawal with receptor selective antagonists. Chronic infusion in nicotine in receptor knock-out mice will confirm the involvement of specific receptor subtypes in nicotine dependence. Moreover, we propose to distinguish between the contributions of peripheral and central nicotine receptors in the development of dependence. Finally, our observations that bupropion has both nicotine agonist and antagonist properties represents an important lead for further exploration of the mechanisms underlying the pharmacological effects of nicotine and the development of dependence. To further investigate the antagonistic effect of bupropion, a number of bupropion analogs as well as its metabolites will be evaluated for antagonism of nicotine effects. Finally, bupropion will be evaluated in mice chronically infused with nicotine to determine whether it alleviates or exacerbates withdrawal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPECIFICITY
COCAINE
DISCRIMINATION
AND
PHARMACOLOGICAL
Principal Investigator & Institution: Rush, Craig R.; Associate Professor of Psychiatry; Behavioral Science; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2001; Project Start 01-MAR-1997; Project End 31-JAN-2003
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Summary: (Applicant's Abstract) The revised application is entitled "Human Cocaine Discrimination: Pharmacological Specificity". The title was changed since less emphasis is given to elucidating the neuropharmacological mechanisms underlying the discriminative stimulus effects of cocaine in human research volunteers. The revised application consists of 5 inpatient, laboratory experiments aimed at characterizing the discriminative stimulus effects of cocaine in humans. Exp. 1 will replicate the only other study that established cocaine as a discriminative stimulus in humans, and extend these findings by testing the discriminative stimulus effects of d- amphetamine and pentobarbital to further determine the pharmacological specificity of the cocaineplacebo discrimination. Exp. 2 will determine the effects of training dose on subsequent discrimination performance. Exp. 3-5 will test the discriminative stimulus effects of 6 compounds (i.e., mazindol, methylphenidate, bupropion, diethylpropion, desipramine and fluoxetine) in cocaine-trained humans. d-Amphetamine and pentobarbital will be included as a positive and negative control, respectively, in each of these experiments. Two training conditions will be used in each experiment to further explore the influence of cocaine training dose on subsequent discrimination performance. Drug-effect and mood questionnaires will be used in each experiment. The experiments proposed in this application have at least 6 important implications. First, these experiments will lay the groundwork for studying the discriminative stimulus effects of cocaine in humans. Second, these experiments will determine the influence of cocaine training dose on subsequent drug discrimination performance. Third, because some of the compounds to be tested exert their effects primarily via dopamine systems (i.e., mazindol, methylphenidate, bupropion, diethylpropion) and others via norepinephrine (i.e., desipramine) or serotonin (i.e., fluoxetine) systems, these experiments will begin to elucidate the neuropharmacological mechanisms underlying the discriminative stimulus effects of cocaine in humans, and whether these mechanisms vary across different training conditions. Fourth, because all of the compounds have previously been tested in nonhuman laboratory animals trained to discriminate between cocaine and vehicle, these experiments will begin to determine, albeit indirectly, to what extent the findings from preclinical studies generalize to humans. Fifth, the inclusion of drugeffect and mood questionnaires will provide ancillary information concerning the relationship between the discriminative stimulus and subjective effects of cocaine. Finally, because the interoceptive and discriminative stimulus effects of cocaine clearly contribute to its abuse, the experiments proposed in this application could provide information relevant to the treatment of cocaine abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOCHROME P450 IN NICOTINE METABOLISM Principal Investigator & Institution: Murphy, Sharon E.; Assistant Professor; Biochem/Mole Biol/Biophysics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (PROVIDED BY APPLICANT) Nicotine is well established to be the addictive agent in tobacco, and its metabolites are chemically well described. Surprisingly, the specific enzymes responsible for nicotine metabolism are rather poorly characterized. In this proposal the role of individual P450s in the metabolism of nicotine and cotinine will be investigated. In most smokers the majority of nicotine is metabolized to cotinine. The first step of this pathway is nicotine 5'- oxidation. Cotinine is metabolized to trans-3'-hydroxycotinine, the major nicotine metabolite excreted by smokers. P450 2A6 is reported to be responsible for both the 5'-oxidation of nicotine and
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Bupropion
the 3'-hydroxylation of cotinine. Nicotine is not exclusively metabolized by P450 2A6, and P450 2A6-catalyzed nicotine metabolism is not specific for 5'-oxidation. We have reported that both P450 2A6 and human liver microsomes (HLM) catalyze the 2'oxidation of nicotine. The product of this reaction is the precursor of the lung carcinogen, NNK. P450 2A13, which is closely related to P450 2A6, is expressed in the lung and is an efficient catalyst of both nicotine 5'-oxidation and NNK metabolic activation. The extent of nicotine 2'-oxidation by this enzyme is unknown. P450 2A 13 could prove to be an important enzyme in NNK induced lung carcinogenesis in smokers. P450 2B6 is also a catalyst of nicotine 5'-oxidation and appears to contribute to nicotine metabolism by HLM. The antismoking agent bupropion is metabolized by P450 2B6. It is proposed that one mechanism of bupropion's action may be its inhibition of nicotine metabolism. Studies to investigate the importance of nicotine metabolism in smoking and the use of metabolism inhibitors to modify smoking behavior are ongoing. For these studies to succeed and to optimize the use of pharmacological agents to help reduce smoking, it is critical to understand all the enzymes involved in nicotine metabolism and to characterize the products of each pathway. The goals of this proposal are to determine the contribution of P450 2A6 and other hepatic P450s to nicotine and cotinine metabolism, to investigate the metabolism of nicotine and cotinine by human lung microsomes and P450s present in the lung, and to determine the specificity of that metabolism by the important P450s in the lung and liver. The hypotheses to be tested are that both nicotine and cotinine are metabolized by P450s other than P450 2A6 and that the specificity of that metabolism will vary among, P450s. The specific aims are: 1) .to determine the role of human hepatic P450s other than P450 2A6 in both nicotine and cotinine metabolism, 2) to characterize the metabolism of nicotine and cotinine by human lung microsomes, 3) to completely characterize the products of nicotine and cotinine metabolism by human lung microsomes, 4) to determine whether bupropion inhibits any of the pathways of nicotine metabolism in HLM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION, ANTIDEPRESSANTS & SYMPATHETIC REACTIVITY Principal Investigator & Institution: Straneva, Patricia A.; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 22-SEP-2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPING MEDICATION FOR TOBACCO ADDICTION: NMDA AGENTS Principal Investigator & Institution: Bisaga, Adam A.; 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-2008 Summary: (provided by applicant): Tobacco addiction is an enormous public health problem. Recent advances in understanding the effects of nicotine on the brain and behavior present an opportunity to advance medication development. Neurotransmission at NMDA receptors is involved in many of nicotine's effects and it is postulated that modulation of NMDA neurotransmission may be effective in the treatment of tobacco addiction. We propose to develop and implement human laboratory models to screen promising medications and establish whether modulation of the NMDA receptor system with memantine, a non-competitive NMDA antagonist,
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has beneficial effects in the treatment of tobacco addiction. For comparison we will test bupropion, an antidepressant with proven efficacy in the treatment of tobacco addiction. Inpatient laboratory studies will include paradigms designed to model several dimensions of tobacco addiction using non-treatment seeking, nicotinedependent smokers. We will assess the effect of chronic treatment with bupropion and memantine in two paradigms that model two main components of tobacco addiction that can be a target for pharmacological modulation. In Study 1 we will model maintenance of cigarette smoking, and assess how medications affect: early tobacco withdrawal, effects of cigarettes in smoking-deprived and non-deprived smokers, reactivity to cigarette cues, and cigarette smoking under unlimited choice conditions and under operational conditions (cigarettes versus money choice). In Study 2 we will develop a laboratory model of smoking relapse induced by cigarette exposure in abstinent smokers, and will compare self-administration behavior after the exposure to the neutral or active cigarette stimulus. In Study 3, we will use a smoking relapse model to assess how medication affects extended withdrawal, the effects of cigarettes in deprived smokers, and self-administration behavior in abstinent participants following cigarette re-exposure. At the conclusion of 5 years, we will be able to develop laboratory models for early-stage testing of new and/or existing compounds for the treatment of tobacco addiction and to further elucidate the neurobiology of nicotine dependence in humans, particularly the contribution of NMDA receptor neurotransmission. This application represents, to our knowledge, the first attempt to systematically evaluate the contribution of NMDA receptor-mediated neurotransmission on nicotine's action in humans from the perspective of medication development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMEMT OF NOVEL TREATMENTS FOR NICOTINE ADDICTION Principal Investigator & Institution: Dwoskin, Linda P.; Professor; Pharmaceutical Sciences; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Tobacco smoking is the number one health problem accounting for more illnesses and deaths in the US than any other factor. Despite efficacy of some current pharmacotherapies (i.e., nicotine replacement and bupropion), relapse rates continue to be high, indicating that novel medications are needed. Research in the current application proposes to develop a new class of subtype-selective nicotinic receptor (nAChR) antagonists as therapeutic agents with efficacy for tobacco use cessation and for treatment of nicotine dependence. As much as tobacco use behavior and nicotine addiction have links to depression, these novel drug candidates may also prove to be new treatments for depression. Based on the observations that the bupropion acts as a nAChR antagonist and that the nonselective nAChR antagonist, mecamylamine, has some efficacy as a tobacco use cessation agent, but is limited by its peripherally-mediated side-effect of constipation, we predict that the subtype-selective nAChR antagonists, which we propose to develop, may have therapeutic advantages and efficacy as tobacco use cessation agents in the treatment of nicotine addiction. We hypothesize that quaternizing the pyridine-N atom of the nicotine molecule with a lipophillic N-substituent to afford N-nicotinium analogs and/or by connecting these quaternary ammonium moieties with a lipophillic linker to afford N,N'-bis-analogs will result in subtype-selective nAChR antagonists, which will inhibit either nicotine-evoked dopamine, norepinephrine or serotonin release, and thus, inhibit nicotineinduced behaviors, indicating their potential as nicotine addiction treatments. Brain
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Bupropion
bioavailability, pharmacokinetics and metabolism of the lead candidates will also be evaluated. Comparison of results using native and recombinant nAChRs will provide new insights into the subunit composition of nAChRs mediating these functions. Drug candidates will be assessed for their ability to decrease nicotine self-administration, to decrease nicotine-induced reinstatement of nicotine seeking behavior, and to precipitate withdrawal in nicotine-dependent animals. Thus, an integrative approach (i.e., medicinal chemistry, pharmacokinetics, metabolism, pharmacology, psychology and neuroscience) will be used to increase our understanding of the underlying mechanisms of tobacco use and nicotine addiction, with focus on pharmacotherapeutic candidate development. PROJECT I "Synthesis Of Novel Analogs" (PI - Dr. Peter A. Crooks) (provided by applicant): Rationale: This research will provide synthetic procedures for the preparation of a series of optimized analogs of our parent compounds: N-ndodecylnicotinium iodide (NDDNI), and N,N'-n-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), developed from initial studies on a series of N-n-alkylnicotinium iodides. Both NDDNI and bPiDDB potently inhibit S(-)-nicotine (NIC)-evoked dopamine (DA) release from native neuronal nicotinic acetylcholine receptors (nAChRs) with Ki values of 9 and 5 nM, respectively. The overall objective of this project is to focus on the design of conformationally restricted analogs of NDDNI and bPiDDB, in order to identify compounds that have high affinity and selectivity as antagonists at nAChR subtypes that mediate NIC-evoked DA release, NIC-evoked norepinephrine (NE) release, and NIC-evoked 5-hydroxytryptamine (5-HT) release. Hypothesis: Modification of the NIC molecule by quaternization of the pyridine-N atom with a lipophillic substituent to afford N-substituted analogs and/or by connecting these quaternary ammonium moieties with a lipophillic linker to afford b/s-analogs will result in nAChR subtype-selective, brain-bioavailable antagonists. In this respect, we hypothesize that altering the NDDNI and bPiDDB molecules to afford more geometrically defined, conformationally restricted analogs will afford potent and selective antagonists at the above nAChRs, and will provide important structural information for determining the antagonist pharmacophores at these various nAChR subtypes. This research will be the first to investigate the characteristics of the respective antagonist pharmacophores for these three neurotransmitter releasing nAChR subtypes. We have also shown that both NDDNI and bPiDDB inhibit brain [3H]choline uptake by the blood-brain barrier (BBB) choline transporter when evaluated in the in situ rat brain perfusion preparation (Allen and Smith, 2001), thus providing an indication of their affinity for the choline transporter and the potential to be transported through the BBB. More importantly, the structurally-related analog, N-n-octylnicotinium iodide (NONI), which has an affinity for the BBB choline transporter of Ki = 49 pM (Km for choline is. 42 uM), has been radiolabeled and shown to access the brain via the choline transporter. Thus, we also plan to evaluate optimized analogs of NDDNI and bPiDDB that show high affinity and selectivity at specific nAChR subtypes for their ability to inhibit brain [3H]choline uptake using the in situ rat brain perfusion methods (Takasato et al., 1984; Allen and Smith, 1999; 2001 ). The most promising antagonists will be radiolabeled and their ability to penetrate the BBB utilizing the choline transporter determined. We will evaluate inhibition by these compounds in 8 brain regions: frontal, parietal and occipital cortex; hippocampus, striatum, thalamus/hypothalamus, cerebellum and pons/medulla. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISEASE MANAGEMENT FOR SMOKERS IN RURAL PRIMARY CARE Principal Investigator & Institution: Ellerbeck, Edward F.; Associate Professor; Preventive Medicine and Public Health; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2003; Project Start 09-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Cigarette smoking and complications from cigarette smoking disproportionately affect people living in rural communities. Previous strategies to promote smoking cessation have largely been urban-based, involved short term interventions, enrolled smokers already motivated to quit, and been poorly integrated into primary care practice. Nicotine addiction may be better conceptualized as a chronic illness that might be most effectively addressed using newer models of chronic disease management. A disease management approach to smoking cessation would provide support for multiple quit attempts, treat smokers of all stages of readiness to quit, and coordinate cessation efforts with primary health care providers. The primary aim of this study is to assess the effectiveness of both high and low intensity, disease management programs for nicotine dependence. In this study, we will recruit 750 smokers from 20 rural, primary care clinics in Kansas. Subjects will be randomly assigned to one of three study arms, each providing 20 months of treatment: C (comparison group), LDM (low-intensity disease management) or HDM (highintensity disease management). Participant's in-group C will receive health educational mailings and an offer for free nicotine replacement therapy (six weeks) or bupropion (seven weeks) every 6 months (months 0, 6, 12, and 18). Participants in LDM will receive the same interventions as C plus a low-intensity disease management program that includes a single telephone counseling session using motivational interviewing (MI)at months 0, 6, 12, and 18 to encourage a cessation attempt and also includes coordination of smoking assessments and pharmacotherapy with the patient's physician. HDM participants will receive C plus a high intensity disease management program that includes up to six telephone-based MI counseling sessions at months 0, 6, 12, and 18 to encourage a smoking cessation attempt and to prevent relapse after a quit attempt, as well as coordination of smoking assessments, quit attempts, and pharmacotherapy with the patient's physician. The primary outcome of the study is 7-day point prevalence abstinence from cigarettes at 2 years after enrollment. Secondary outcomes include: 1) number of quit attempts and 2) progress in stage of change. If successful, this intervention will provide a generalizable model for addressing nicotine dependence that could improve long-term management of smoking in primary care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOES BUPROPION HELP AFRICAN AMERICANS QUIT SMOKING? Principal Investigator & Institution: Ahluwalia, Jasjit S.; Chair and Director of Research; Psychology and Sociology; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 30-JUN-2002 Summary: The primary aim of this study is to assess the incremental benefit of adjuvant behavioral therapy with the transdermal nicotine patch (TNP) for smoking cessation in inner-city African Americans. This 4 year randomized intervention trial will be conducted at two community-based clinics. The primary outcome of the study is biochemically-verified continuous abstinence from cigarettes at 6 months from the endof-treatment. Secondary outcomes include 1) continuous, 30-day, and 7-day abstinence
30
Bupropion
at one year; 2) differences among, and within, the three groups in advancing along the stages of change continuum; and, 3) cost-effectiveness, as measured by cost-persuccessful quitter. This two arm study has one comparison group (c) and one intervention group (Tx1). Group 1 (Comparison = C) will receive usual care, typical of a primary care setting, consisting of brief physician advice and a previously developed culturally-sensitive smoking cessation guide written at the sixth grade reading level (Pathways to Freedom). Group 2 (Boosted Self-Help = Tx1) will receive the same as C with the addition of a culturally-sensitive smoking cessation video (Kick-It!), a baseline individual counseling session, and four stage-based booster phone calls, the goals of which are, to encourage quitting, to increase use of the written and audiovisual materials, and to maintain compliance with TNP. There will be six data collection points: 1) at screening, in person; 2) at baseline, in person; 3) at 6 weeks, in person; 4) at 10 weeks (the end-of-treatment), by telephone; 5) at six months, in person; and, 6) at one year, by telephone. Recruitment and retention of subjects will be enhanced by phone and mailed reminders to pick up remaining TNP at six weeks and to return for the six month visit, by a monetary stipend for return at the sixth month visit, and by home visits at six months for no shows. The intervention groups have been designed so that efficacy, durability, and generalizabilty, can be accurately measured and assessed. This randomized controlled trial will use the patient as the unit of randomization and analysis. We project that 400 smokers for C, and 400 for Tx1, a total of 800 patients, will be required at baseline to detect proposed treatment effects for the primary outcome with a power of 80%. Ultimately, we envision that the interventions, if efficacious, could be used as a pre-packaged intervention and be distributed at settings such as churches and social service agencies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG ABUSE, COUNSELING
DEPRESSION AND
RESPONSES
TO
HIV
Principal Investigator & Institution: Marmor, Michael; Environmental Medicine; New York University School of Medicine 550 1St Ave New York, NY 10016 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant) The long-term objective of this research is to reduce the incidence of infection with human immunodeficiency virus type 1 (HIV) in industrialized countries by developing methods to identify and treat high-risk individuals whose response to HIV testing and counseling is hindered by psychopathology. The project's specific aims are (1) to describe the distribution of psychopathologies among persons undergoing HIV testing and counseling, and (2) to test the hypotheses that high-risk, HIV-seronegative persons with mild-to-moderate depression will be more likely to adopt protective behavior changes when provided with pharmacotherapy for their depression than when treated with placebo. The study design to achieve specific aim 2 will be a randomized, double-blinded clinical trial of bupropion hydrochloride versus placebo administered for a total of 7 months. The study population will be initially high-risk, HIV-seronegative men who have sex with men (MSM). Individuals who are ineligible or decline entry into the clinical trial will be entered into an observational study. The primary outcome measure of the clinical trial will be self-reported numbers of partners in unprotected receptive anal intercourse. Secondary outcomes will be substances used and frequency of substance use by selfreport and toxicology; (c) new infections with sexually transmitted infections including gonorrhea, syphilis, Kaposi's sarcoma-associated herpesvirus, and hepatitis C virus (HCV) and HIV; and (d) measures of psychological factors that have been shown to be,
Studies
31
or are thought to be, associated with HIV incidence rates, including measures of selfefficacy, self-esteem, stage of change, and depression. Enrollment data from the observational study will be combined with enrollment data from the clinical trial to provide a description of the distribution of psychopathologies and substance abuse among high-risk MSM. Longitudinal data form the observational study will be used to assess the associations of psychopathologies, substances used and frequency of substance use with adverse outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS ACTIVATION
OF
DEPRESSION
TREATMENT
ON
PLATELET
Principal Investigator & Institution: Markovitz, Jerome H.; Medicine; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2003 Summary: (adapted from investigator's abstract): The primary objective of this study is to assess the effects of standard pharmacologic treatments of the clinical depression on platelet activation PA). Increased PA is present in clinical depression, and has been implicated as one mechanism that may explain the link between depression and coronary heart disease (CHD) events. The investigators' preliminary work indicates that platelet secretion in increased in clinical depression, and that pharmacologic treatment with the selective serotonin reuptake inhibitor sertraline attenuates this increase. They also found evidence that depressed patients with a family history of CHD have increased PA. In the present application, the investigators seek to extend these findings by (a) performing a double-blind, placebo-controlled trial of sertraline and (b) assessing the effects of another pharmacologic treatment for depression (bupropion) on PA. As in previous studies, PA will be assessed by state-of-the-art flow cytometric detection, using methods developed and standardized in our laboratory. After initial PA testing, a total of 180 patients will be randomized to receive either sertraline or placebo for 8 weeks, with retesting at the end of this time period. A control group of 70 nondepressed individuals of similar age and gender composition will also be tested twice over 8 weeks. After follow-up measures for PA are taken, the blind will be broken and patients previously on placebo will be given 8 weeks of treatment with bupropion (an antidepressant medication that affects dopamine and norepinephrine pathways without affecting serotonin pathways). A final PA measure will be performed at the end of this 8-week treatment, in order to a) assess the stability of the response to sertraline and b) assess the open-label effects of bupropion. The investigators anticipate that 144 subjects will complete the entire protocol. The hypotheses for the study are: (1) PA is increased in depressed patients relative to controls, with the highest levels found among depressed patients with a family history of CHD; (2) Sertraline decreases PA in depressed patients relative to placebo; and (3) Bupropion, an antidepressant with nonserotonergic mechanisms of action, also decreases PA. This work will contribute to the understanding of mechanisms and treatment for depression so as to diminish CHD risk, particularly among those with a family history of CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFICACY OF BUPROPION FOR TREATING SPIT TOBACCO USERS Principal Investigator & Institution: Dale, Lowell C.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006
32
Bupropion
Summary: Although overall rates of cigarette smoking have declined over the past 40 years, the use of spit tobacco (ST) has tripled. The use of ST can lead to nicotine addiction and physical dependence. ST use is known to increase the risk of periodontal disease and oral cancer. Moreover, ST use increases the risk for cancer of the esophagus, larynx, stomach and pancreas and the risk of cardiovascular disease. Effective interventions are needed to assist ST users to stop. Bupropion, a monocyclic antidepressant that inhibits the neuronal re-uptake of norepinephrine and dopamine and may also selectively inhibit neuronal nicotinic receptors, has demonstrated efficacy for smoking cessation. In a placebo-controlled pilot study, we have shown possible treatment effects of sustained release bupropion (SR) in ST user. Our aims are: 1) To evaluate the efficacy of a 12-week course of bupropion SR rates of abstinence from all tobacco use; 2) To evaluate the efficacy of a 12-week course of bupropion SR compared to placebo on the end of treatment and 12- month rates of abstinence from all tobacco use; 2) To evaluate the efficacy of a 12-week course of bupropion SR compare to placebo on the end of treatment and 12-month rates of abstinence from ST; 3) To determine what baseline characteristics in addition to medication assignment are associated with abstinence from all tobacco and from ST, at the end of treatment and at 12 months; 4) To determine the association between baseline urine tobacco alkaloids with self-reported tobacco use behavior and level of nicotine dependence assessed using the Fagerstrom Tolerance Questionnaire modified for ST users; 6) To determine if ST users successful in abstaining from ST switch to a nicotine-replacement product or a different tobacco product (cigarettes, pipe, or cigars). In a randomized, double-blind, placebo-controlled trial, we will compare bupropion SR to placebo in 320 regular users of ST. Active or placebo bupropion will be taken for a total of 12 consecutive weeks starting one week before the target quit date. Behavioral intervention will be provided for all subjects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FRAMING MESSAGES FOR SMOKING CESSATION WITH BUPROPRION Principal Investigator & Institution: Salovey, Peter; Chris Argyris Professor; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: Perhaps one of the reasons why smoking continues despite the welldocumented benefits of quitting is the persuasive messages encouraging smoking cessation tend to focus on the costs of smoking rather than on the benefits of not smoking. These messages are usually designed to elicit feelings of threat or fear by presenting the negative consequences of smoking. On the other hand, messages emphasizing the benefits of smoking cessation may be more motivating for cessation. In general, appeals aimed at persuading individuals to perform a particular health behavior can be framed in different ways. Gain-framed messages present the benefits that are accrued through adopting the behavior (e.g., "If you stop smoking you will find you have more energy"). Loss framed messages covey the costs of not adopting the requested behavior (e.g., "If you do not stop smoking, you will find that you are often out of breath"). Although these two messages convey essentially the same information about smoking cessation, in certain circumstances, one of these messages may be more influential. Across a wide range of studies of health behaviors, gained-framed messages appear to be more appropriate when encouraging a prevention behavior (i.e. smoking cessation), but loss- framed messages appear to be more appropriate when encouraging a prevention behavior (i.e. smoking cessation), but loss-framed messages appear to more appropriate when encouraging a prevention behavior (i.e. smoking cessation), but loss-
Studies
33
framed messages appear to have more impact when encouraging an early-detection (screening) behavior (i.e. mammography). The primary goal of this project is to investigate whether gain-versus loss-framed messages are more influential in encouraging individuals to complete a six-week trial of bupropion SR therapy for smoking cessation and in smoking cessation itself. We hypothesize that gain-framed messages will be more effective in promoting smoking cessation with bupropion SR than loss-framed messages, even though many of the slogans, warnings, and other print information directed toward smokers are loss-framed. A secondary aim of the study will be to examine the relative value of gain framed and loss framed messages in relationship to characteristics of the smoker, including history of cancer, gender, depression, and alcohol use. Finally, the durability of message framing effects will be evaluated using data from three and six month follow-ups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISORDERS
INTEGRATED
TREATMENT
FOR
COCAINE
AND
MOOD
Principal Investigator & Institution: Schmitz, Joy M.; Professor; Psychiatry and Behavioral Scis; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 01-JUN-1994; Project End 30-JUN-2004 Summary: (Applicant's Abstract) Major depression co-occurs commonly in the population of cocaine dependent patients. Despite high prevalence and negative consequences on illness course and prognosis, little is known about effective treatments for dual diagnosis. Traditional models treat each disorder separately, an approach that has proven ineffective. The proposed study provides a direct and logical extension of our previous research evaluating treatments that focus simultaneously on cocaine and mood disorders using integrated cognitive behavioral therapy (CBT) and antidepressant therapy. The study will employ a double-blind, placebo-controlled design in which depressed, cocaine-dependent patients will be randomized into one of four treatment conditions according to a full W factorial research design. Two levels of psychotherapy will compare integrated CBT and Clinical Management (CM) for depression and substance use. Two levels of pharmacotherapy will compare bupropion 400 mg/d and placebo. Dually-diagnosed subjects (N=140) will be treated for 12 weeks, then followed for 12 months. The design provides sufficient power to test both the independent and interactive effects of psychotherapy and pharmacotherapy. The integrated CBT is based on concepts and techniques shared by both Marlatt's Relapse Prevention model of substance abuse and Rehm's Self Control model of depression therapy. Data collected during the original funding period support the feasibility and potential utility of the integrated CBT approach and warrant progression to a larger-scale Stage II efficacy study. The CM approach adapted for this study will provide nonspecific elements of psychotherapy (e.g., support, education, empathy, and advice) and thus serve as an adequate psychotherapy-control condition. Our rationale for testing bupropion is based on its specific dopaminergic activity, efficacy as an antidepressant, low side-effect profile, and preliminary evidence of positive response in depressed cocaine-abusing patients. The study is technically rigorous, theoretically innovative, and scientifically significant. Careful screening and structured clinical interviewing will be used to collect information for making reliable and valid diagnostic judgments of cocaine dependence and current comorbid mood disorder based on DSM-IV criteria. Written therapy manuals, trained therapists, competency checks, and adherence rating scales will be used to verify treatment fidelity. Procedures to safeguard against adverse events will include initial medical evaluation, monitoring of medication plasma levels, daily
34
Bupropion
recording of pill taking using an electronic medication dispensing unit, twice-weekly clinic visits, and regular contact with study psychiatrists. The assessment battery captures the domains of diagnoses, substance use patterns, mood symptomatology, addiction severity, and psychosocial functioning. Primary outcome measures will be cocaine use (via observed urine samples) and depression ratings (BDI, HDRS). Repeated assessments at 3-, 6-, 9-, and 12-months following treatment will be used to evaluate relapse rates, patterns, and predictors. This research will contribute important new theoretical and empirical information concerning efficacious treatment for cocaine dependent patients with comorbid mood disorders. Further, these studies will enhance our knowledge about the relation between dual disorders, the relative effects of treatment on mood and substance use outcomes, and the optimal combination of pharmacologic and psychotherapeutic treatments for this important subpopulation of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERVENTIONS FOR TOBACCO DEPENDENT ADOLESCENTS Principal Investigator & Institution: Hatsukami, Dorothy K.; Professor of Psychiatry; None; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant) Approximately 40-80 percent of adolescent daily smokers have tried to quit smoking, but have been unsuccessful. Present treatments for adolescent smokers have not produced high rates of tobacco abstinence. On the other hand, a significant number of young smokers who have failed to achieve abstinence have been able to reduce their levels of smoking. Few studies have examined the course of these outcomes and whether intervention focusing on reducing or sustaining reduced smoking among the adolescent who cannot quit would produce more effective longterm treatment results. The goal of this grant proposal is to determine whether treatment aimed at smoking reduction among adolescents unable to quit is a viable method of intervention. Two studies are proposed. The first study will determine effective methods for smoking reduction. Adolescents uninterested in quitting will be randomized to one of four conditions for a period of 4 weeks: 1) placebo medication, 2) nicotine patch, 3) nicotine gum, and 4) bupropion. Outcome measures will include compliance to the method of treatment and extent of smoking reduction. The second study will involve a tobacco exposure reduction intervention among those adolescents unable to quit smoking. All adolescents enrolled in the study will be provided smoking cessation treatment. Those adolescents who are unsuccessful will be randomly assigned to an intervention focusing on reduction of smoking or usual care. Those assigned to the reduced smoking intervention will be provided the treatment method(s) that are demonstrated to be efficacious in reducing smoking in the first study. The usual care group will be seen for the same frequency of treatment visits as the reduction group to control for clinic contacts. Follow-up will occur with all groups (successful abstainers and those randomly assigned to interventions) at 12, 26 and 52 weeks. The outcome measures will include a comparison between the reduction intervention group and the usual care on: (1) extent of cigarette reduction and percent who reduce by > 50 percent of baseline; (2) the percent of adolescent smokers who eventually become abstinent from smoking; and (3) the course of treatment outcome. We hypothesize that those individuals who are assigned to tobacco reduction treatment condition compared to the usual care condition will sustain a reduced level of smoking and experience greater eventual success in achieving abstinence.
Studies
35
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIGHT SMOKING PROGRAM Principal Investigator & Institution: Gariti, Peter; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The percent of current lighter smokers has dramatically increased in the past decade. While the risks of smoking are thought to be dose related, the health risks of lighter smoking are nonetheless substantial. It is generally assumed that lighter smokers have an easier time quitting than heavier smokers, but systematic studies comparing the effectiveness of different forms or amounts of treatment have not been conducted. The primary goal of the proposed research is to compare and determine the efficacy and cost effectiveness of two different types of medications (nicodermal patch + dummy bupropion, bupropion + dummy patch) used in conjunction with two levels of psychosocial intervention (10 weeks of 1015 minute individual psycho educational counseling vs. four weeks of 5-minute sessions of individual medication management counseling) in a diverse population of lighter smokers. Four groups of 65 participants each will be compared using a 2 X 2 doubleblind, double-dummy design. The total medication treatment period will be 9 weeks with a target quit date set for day 8 in each condition. Completion of treatment and smoking cessation at 12, 26, and 52 weeks post-treatment initiation will be the primary measures of efficacy for each condition along with cost-effectiveness. Secondarily, the study will attempt to delineate mediators associated with the different treatment conditions (medication compliance, participant views and use of self-help written material and counseling) using self-report questionnaires administered to all participants at weeks 12, 26, and 52. The research will also attempt to: 1). determine the extent to which baseline nicotine dependence severity scores (Fagerstr6m Test for Nicotine Dependence) are a negative predictor of treatment response; 2). determine whether participants with a prior history of heavier smoking respond less favorably than those without such a history; 3). determine if patients who receive bupropion exhibit greater increases in positive affect and greater decreases in negative affect, 4).determine whether any sociodemographic, psychiatric or treatment response (e.g., withdrawal symptoms, adverse events, weight gain, treatment satisfaction) characteristics of the participants are predictive of treatment response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SMOKERS
MAINTAINING
ABSTINENCE
IN
CHRONIC
CIGARETTE
Principal Investigator & Institution: Hall, Sharon M.; Professor & Vice Chair; Langley Porter Psychiatric Institute; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The overall goals of this line of research are to treat chronic cigarette smokers and to understand the processes related to smoking and relapse in these smokers. Combined treatment with antidepressants, nicotine replacement therapies (NRT), and psychological intervention produces high initial abstinence rates. Our ongoing work suggests that extended treatment can maintain these rates, achieving abstinence rates greater than or equal too 60% at one year. A series of hypotheses about the efficacy of extended antidepressant treatment and an
36
Bupropion
empirically based behavioral relapse prevention intervention will be tested. There are five experimental conditions. Chronic smokers (N=400) receive 12 weeks of combined pharmacological treatment (sustained release bupropion + nicotine patch) and psychological intervention, and then are randomly assigned to one of five conditions in a placebo-controlled, double-blind design: (1) 40 weeks active bupropion with medical management (Active/MM); (2) 40 weeks placebo drag with medical management (Placebo/MM); (3) 40 weeks bupropion + behavioral relapse prevention (Active/RP); (4) 40 weeks placebo + behavioral relapse prevention (Placebo/RP); (5) no farther treatment (Brief Treatment). The innovative behavioral relapse prevention intervention will focus on five areas generally agreed to be important post-cessation. These are fluctuating motivation, depression, withdrawal/dependence, weight gain and social support. Participants will be assessed at baseline on smoking behavior, nicotine dependence, psychiatric diagnosis, demographics and measures of anger, anxiety, depression, mood disturbance, social support, stress, health status, motivation for change, and drug and alcohol use. At weeks 12, 24, 36, 52, 64, and 104, participants will be assessed on self-reports of smoking verified by carbon monoxide and anatabine/anabasine assays, as well as on psychometric measures. The proposed research will address significant issues in the treatment of poor prognosis smokers, including the development of strategies to maintain abstinence, determination of the efficacy of extended pharmacological treatment, and determination of the efficacy of a behavioral relapse prevention intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAINTENANCE TREATMENT FOR SMOKING CESSATION Principal Investigator & Institution: Killen, Joel D.; Associate Professor; Medicine; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2005 Summary: (investigator's abstract): Four hundred adult smokers will be enrolled in the study. The primary goal is to compare 2 strategies designed to promote longer-term maintenance of smoking cessation. Each strategy will include an acute treatment phase and a maintenance treatment phase. All smokers will receive the same "Acute Phase Treatment." In this acute phase, all smokers will receive treatment for nicotine dependence that combines nicotine patch (21mg), bupropion (300mg), and relapse prevention training (RPT). During the acute phase, nicotine patch will be provided for a total of 8 weeks and bupropion and RPT will be provided for a total of 9 weeks. Following the acute treatment phase, participants will enter a "Maintenance Treatment Phase." During maintenance treatment, half of the participants (n=200) will receive an additional 16 weeks of therapy with bupropion. The other half (n=200) will receive matching placebo. Primary hypothesis: Participants who receive bupropion during the maintenance treatment phase will have a higher abstinence rate at l2mo follow-up than participants assigned to receive matching placebo. Abstinence will be defined as a report of non-smoking (not even a puff) for 7 consecutive days prior to contact plus a saliva cotinine level below 20 ng/ml. With 200 participants per cell, we will have, in general, 80 percent power at a 2-tailed alpha of .05 to detect a difference in abstinence rates of at least 15 percent over a large range of success probabilities. Secondary objectives: we propose to genotype all subjects for polymorphisms at loci hypothesized to affect nicotine dependence and/or bupropion efficacy. These include CYP2D6, the serotonin transporter, the dopamine transporter, dopamine D2 receptor, and the dopamine D4 receptor. Analyses will examine whether polymorphisms at these loci moderate response to treatment. The proposed study will address several important
Studies
37
gaps in our knowledge. First, our proposed study would be perhaps the first to evaluate the efficacy of an antidepressant medication as maintenance therapy in the treatment of nicotine dependence. Second, this study would be among the first to examine the efficacy of a treatment for nicotine dependence combining nicotine replacement and antidepressant medication. Third, to our knowledge this may be the first prospective trial of smoking cessation techniques in which genetic data are included as predictors of outcome. In general, this study will provide important practical information to the medical and health communities concerning the utility of longer-term therapy with antidepressant medication for smoking cessation and will advance our knowledge of the underlying relationship of nicotine addiction and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAKING A BETTER BUPROPION Principal Investigator & Institution: Reinhard, John F.; Senior Research Scientist; Trelion Pharmaceuticals, Inc. Box 14587, 2 Davis Dr Research Triangle Park, NC 27709 Timing: Fiscal Year 2002; Project Start 10-APR-2002; Project End 31-OCT-2002 Summary: (provided by applicant): Bupropion is a safe and generally well-tolerated treatment for depression and nicotine dependence when used in doses 95 percent of circulation OHB is the levorotatory enantiomer (-OHB). Studies, in-house, have demonstrated that -OHB is devoid of therapeutic activity but is 3-fold more toxic than +OHB. The present proposal is predicated on the hypothesis that formation of -OHB is enantioselective from (S)-bupropion and that the metabolism of (R)-bupropion, while much less acile, primarily results in +OHB. Studies, with human microsomes, are proposed to test this hypothesis. If successful, a Phase II submission will request support to conduct a proof-of-concept study in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MARIJUANA PHARMACOTHERAPIES: CONTROLLED CLINICAL TRIALS Principal Investigator & Institution: Mc Dowell, David; Medical Director, Stars; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-MAR-2004 Summary: (Applicant's Abstract) Cannabis preparations are the most commonly used illicit substances in the United States. In recent years, rates of marijuana use and, in turn, dependence have been rising, especially among younger people. Heavy and chronic use of marijuana carries with it substantial morbidity. In the years to come, cannabis dependence will likely become an even more severe and prevalent health problem. Compared to other substances of abuse, the treatment of heavy and chronic marijuana use (dependence) has received comparatively little investigation. There are very few controlled treatment trials for cannabis dependence. Recent animal and human laboratory studies have characterized substantial withdrawal symptoms associated with the abrupt cessation of marijuana. These symptoms are characterized by a range of effects that include anxiety, irritability, somatic complaints, and difficulty sleeping. The symptoms associated with marijuana withdrawal resemble both depression and nicotine withdrawal, suggesting the utility of a pharmacological intervention. We propose a carefully constructed double-blind placebo-controlled trial testing two agents, bupropion and nefazodone, in the context of psychosocial intervention. We hypothesize
38
Bupropion
that reducing withdrawal symptoms will result in greater retention in treatment and lead to higher rates of abstinence in treatment seeking marijuana users. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR NEUROBIOLOGY OF DEPRESSION Principal Investigator & Institution: Shelton, Richard C.; Psychiatry; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: This is a request for five years of salary support via the Midcareer Investigator Award in Patient-Oriented Research (K24). Throughout my career I have sought to bridge basic neurobiological and clinical domains, with special emphasis on mood disorders. By the early 1990's, I began to redirect my energies toward the development of a series of studies using newer molecular biological methods to investigate the causes and possible treatments for depression. Using a fibroblast cell culture model, my collaborators and I have discovered that melancholic major depressives have a reduction of cyclic AMP binding to the regulatory subunit of protein kinase A (PKA) linked to beta adrenoceptors. This results in a concomitant reduction in phosphorylation activity (including that of CREB) and altered gene expression. We also have shown an altered expression of a specific nuclear phosphatase gene using the differential display reverse transcription polymerase chain reaction methodology with cPCR. Herein, I have outlined these findings along with plans for related projects over the next five years. I also have described briefly two other project areas that stand in the mid-ground between basic and clinical investigations. One is an investigation of mood regulation using new clinical ratings instruments (developed, in part by our research group) to measure components of mood under conditions of pharmacological manipulation. The second represents a novel therapeutic intervention in refractory major depression. Drawing from a set of basic laboratory observations, I have conducted a successful trial of the combination of olanzapine and fluoxetine in refractory depressives. Together, these study areas demonstrate my capacity to bridge from basic laboratory findings, on the one hand, to clinical phenomenology and treatment, on the other. Finally, consistent with the goals of the K24, I have a long track-record of mentorship of new investigators from a number of disciplines. However, an increasing burden of administrative and clinical responsibilities threatens my research productivity and mentorship. This award will relieve me of many of these demands and will allow me to: 1.Develop further expertise in basic molecular biological methods; 2. Develop new projects oriented to future funding opportunities; and 3. Continue to mentor the next generation of investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: NEGATIVE AFFECT TREATMENT MEDICATION
IN
RELAPSE:
WITHDRAWAL
AND
Principal Investigator & Institution: Baker, Timothy B.; Professor; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: (Applicant's Description) Numerous smoking cessation treatments have been developed over the past 20 years. Unfortunately, these have not led to a notable increase in cessation rates over the same period. One impediment to a rational, empirically-based approach to smoking treatment is that we know very little about how effective treatments work. The proposed research will use Electronic Diaries (EDs; palmtop
Studies
39
computers) to gather fine-grained, virtually real-time information on variables thought to mediate the effects of efficacious smoking cessation treatments. In addition, recent research suggests that tonic change in affect/withdrawal powerfully predicts relapse; this project will permit sensitive tests of this relation. In this research, 390 smokers motivated to quit will be randomized to one of three groups. In the Bupropion group, smokers will attempt to quit smoking with the aid of bupropion pharmacotherapy (150 mg b.i.d.). In the Combined condition, smokers will receive bupropion pharmacotherapy and will participate in group therapy sessions comprising therapeutic elements of known efficacy (i.e., social support and coping-skills training). A final group of smokers will be assigned to a Placebo condition; these subjects will not attend group sessions and will be given placebo pharmacotherapy. All subjects will use EDs to collect real-time information about urges, withdrawal, negative affect, smoking rates, etc -during a 4-day period prior to the quit date and for the first 8 weeks of the cessation attempt. The study design allows for sensitive descriptive and predictive examinations of both short-term episodes and longer-term trends in theoretically prominent variables such as negative affect, withdrawal, stressors, temptations, and urges. It also permits tests of mediation to determine whether bupropion pharmacotherapy and/or counseling work through modifying the timing, frequency, trends, and/or severity of such variables. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE AND SMOKING CESSATION IN SCHIZOPHRENIA Principal Investigator & Institution: Evins, Anne E.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Abstract) This proposal focuses on providing the candidate with the expertise needed to bridge several disciplines in the study of pharmacologic and behavioral interventions in the treatment of nicotine addiction in schizophrenia. Nearly 90 percent of patients with schizophrenia smoke cigarettes compared to less than 25 percent of the general U.S. adult population. Compounded by the problem that patients with schizophrenia are less likely to receive adequate routine and preventative medical care, heavy smoking represents a significant and neglected public health problem for people with schizophrenia. In pilot trials, the candidate found bupropion SR to be safe and effective for smoking reduction and cessation in patients with schizophrenia while improving negative and depressive symptoms and preventing weight gain and exacerbation of psychosis. In the proposed study, 60 subjects with schizophrenia who smoke greater than 10 cigarettes per day and wish to quit smoking will be randomized, in double blind fashion, to receive either bupropion SR or placebo for twelve weeks, combined with a nine week cognitive behavioral Quit Smoking Group Therapy Program modified by the candidate for patients with schizophrenia. The primary outcome measure is 7-day point prevalence of greater than or equal to 50 percent smoking reduction at the end of 12 weeks treatment that is biochemically confirmed. Secondary outcome measures are 7-day point prevalence tobacco abstinence at the end of the 3 month treatment and 3 month follow up phases, sustained tobacco abstinence or reduction, change in psychiatric symptoms, cognitive functioning, weight, side effects and health related quality of life. Career Development Plan: The candidate will build upon her experience conducting treatment trials for negative symptoms of schizophrenia. With consultation from individuals with the appropriate expertise, the candidate will design, implement and interpret pharmacologic intervention trials for smoking cessation in schizophrenia, study of cognitive behavioral therapy interventions
40
Bupropion
in patients with the dual diagnoses of addiction and major mental illness, study of harm reduction strategies in patients with schizophrenia unable to attain abstinence, and studies of the effect of nicotinic agents on attention and memory in schizophrenia that will lay the foundation for future independent investigation by the candidate in these areas. The mentored investigative work will take place at the Massachusetts General Hospital and will complement an intensive training program of coursework at the Massachusetts General Hospital and the Harvard School of Public Health on methodology, epidemiology, statistics, and responsible conduct of research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CESSATION
NOVEL
LAPSE-RESPONSIVE
APPROACH
TO
SMOKING
Principal Investigator & Institution: Stitzer, Maxine L.; Professor of Behavioral Biology; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 05-SEP-2000; Project End 31-AUG-2003 Summary: (Applicant's Abstract) This treatment development project will provide valuable information about a novel approach to smoking cessation that intervenes aggressively with poor prognosis smokers who have had a smoking lapse during the first two post-cessation weeks. The model is based on previous observations that early smoking lapse is a powerful predictor of failure in smoking cessation attempts. It utilizes the most potent available empirically tested behavioral techniques, rapid smoking and counseling, combined with bupropion pharmacotherapy, to test a new lapse-contingent model of intervention. Rapid smoking with counseling is expected to counteract some of the adverse cognitive and physiological effects of self-initiated early smoking lapses through counter-conditioning. During the 3-year treatment development project we will 1) write a manual describing the new lapse-contingent rapid smoking plus counseling intervention, 2) train an appropriate staff member to administer the therapy, 3) implement therapist adherence and competency assessments, 4) conduct an open pilot study (n=12) of the new therapy, 5) make interim protocol and manual alterations as needed, and 6) evaluate the new treatment in a small sample (n=63) pilot study in which lapsers are randomly assigned to the full intervention, to intensive counseling only or to a control condition with no special intervention following their first post-cessation smoking lapse. Our hypothesis is that those receiving the full intervention with rapid smoking will have significantly better outcomes than either of the control groups at all follow-up time points (1, 3 and 6 months postcessation). The novel concept here is to obtain more reliable initiation and early postcessation abstinence, without which long-term success appears unlikely, by proactively intervening with those who do have an early smoking lapse in an attempt to improve their prognosis. Therapeutic procedures that reduce or reverse the detrimental effects of early lapse could be a significant breakthrough in improving smoking cessation rates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPIATE AND NICOTINE DEPENDENCE--MEDICATIONS AND THERAPY Principal Investigator & Institution: Sullivan, Maria A.; Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 30-JUN-2004
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Summary: Heroin and nicotine dependence are two addictions for which new combined pharmacotherapy/behavioral therapy interventions are possible. The goal of this mentored clinical scientist award is to promote the developing research skills of Maria A. Sullivan, M.D., Ph.D., by providing two areas of clinical research for testing novel combined medication/therapy strategies for opiate and nicotine dependence. Dr. Sullivan, a Board-Certified Psychiatrist, has completed a successful research fellowship in the Division on Substance Use at Columbia University/New York State Psychiatric Institute (NYSPI). As a fellow, Dr. Sullivan has begun studying patterns of smoking among schizophrenic patients and carried out a pilot intervention using bupropion/behavioral therapy to treat nicotine dependence among patients with chronic psychosis. This year Dr. Sullivan has joined the staff in the Division as an Assistant Professor of Clinical Psychiatry. She is currently serving as the Co-Director for the NIDA funded grant, "Opiate Dependence: Combined Naltrexone/Behavior Therapy." In the next several years, Dr. Sullivan plans to carry out clinical treatment trials to explore novel combined pharmacotherapy/psychotherapy approaches to opiate and nicotine dependence. Her proposed research plan will enable her to develop skills in two specific areas of addiction psychiatry: (1)conducting double-blind pharmacotherapeutic trials of agents which target specific mood symptoms in opiate or nicotine dependence or withdrawal; and (2)developing manualized psychotherapies tailored to promote abstinence and relapse prevention for individuals abusing certain classes of drugs. In this way, Dr. Sullivan will be well prepared to achieve her long-term research career goal of developing treatment approaches for comorbid substance use/psychiatric disorders. Under the sponsorship and guidance of Dr. Herbert Kleber, together with the faculty and resources available at Columbia University, Dr. Sullivan's training plan combines formal course work with clinical research experience at several sites of the New York State Psychiatric Institute. She will be working closely with several preceptors to receive training in the following areas: design and methods of clinical treatment studies; controlled medication trials; developing and implementing manual-guided relapse prevention therapies for opiate and nicotine dependence in selected populations; and biostatistics and epidemiology. Her specific research plan includes double-blind placebo-controlled trials of bupropion for nicotine dependence and nefazodone with open-label naltrexone for opiate dependence. For both treatment studies, manual-guided relapse prevention therapies will be developed and implemented. Dr. Sullivan's planned research will provide her with unique training and will afford her the opportunity to develop a clinical research career focused on developing new combined medication/therapy approaches to the treatment of substance abuse disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPTIMIZING TREATMENT FOR SCHIZOPHRENIC SMOKERS Principal Investigator & Institution: George, Tony P.; Assistant Professor of Psychiatry; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-MAY-2005 Summary: (provided by applicant) Schizophrenic patients have high co-morbid rates of cigarette smoking (up to 90 percent), and are typically nicotine dependent smokers who have great difficulty quitting smoking. This may relate to improvement of extrapyramidal side effects, cognitive dysfunction and information processing deficits by cigarette smoking, as well as shared genetic factors between the two disorders. Over the past three years, our research program has studied the effects of cigarette smoking on clinical and cognitive function in schizophrenic smokers, and the development of
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pharmacological and behavioral treatment approaches. These studies have suggested that: 1) the atypical antipsychotic clozapine may reduce smoking consumption in schizophrenic outpatients; 2) atypical antipsychotic drugs are superior to typical antipsychotic drugs in combination with the nicotine patch for smoking cessation in treatment-motivated schizophrenic smokers; 3) cigarette smoking may enhance some aspects of cognitive function in schizophrenic patients, and; 4) the anti-smoking agent bupropion (Zyban) appears to be safe and effective for treatment of nicotine dependence in schizophrenia. These findings could have important health benefits for schizophrenic patients, as many often die prematurely from smoking-related medical illness. Furthermore, our findings also suggest that nicotinic receptor mechanisms may be important in the biology of schizophrenia. In this randomized, double-blind trial, we propose to study optimal strategies for smoking cessation in n=100 nicotine dependent outpatient schizophrenic smokers. We will compare bupropion (n=50) to placebo (n=50), in combination with nicotine patch and a specialized group therapy program, for smoking cessation in these patients. The effects of antipsychotic medication class (atypical versus typical antipsychotic) on treatment responses will also be evaluated. Our predictions are that: 1) Bupropion will be superior to placebo for smoking cessation in schizophrenia; 2) atypical versus typical antipsychotic treatment status will enhance smoking cessation outcomes in these patients. The results of this study could provide valuable information on effective medication treatments for cigarette smoking in schizophrenic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGICAL AIDS FOR INTERACTIVE SMOKING CESSATION Principal Investigator & Institution: Swartz, Lynne H.; Oregon Center for Applied Science 1839 Garden Ave Eugene, OR 97403 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2003 Summary: Pharmacological aids such as nicotine replacement (NR) products and buproprion (Zyban) have been demonstrated to be efficacious under FDA-specified conditions. However, despite the improved success in stopping smoking associated with using such products, many people either do not use them or do not use them properly. The primary aims of this project are to develop and test a tailored multimedia intervention designed to improve smoking cessation success by: a) motivating cigarette smokers to use pharmacological aids such as NR products and Zyban, b) assisting them in choosing the type of pharmacological aid best suited to them, and c) ensuring that they employ optimal technique for the use of the chosen pharmacological aid. In Phase I, a complete NR/Zyban intervention segment tailored for the older, Caucasian, female subpopulation was produced for use with our previously developed interactive multimedia smoking cessation programs. The efficacy of the segment was demonstrated in a randomized-control trial. In Phase II, we will develop pharmacological intervention materials explicitly tailored to the characteristics and needs of eleven other subpopulations (using three dimensions: age, race/ethnicity, and gender). The pharmacological intervention materials developed in Phase II will be disseminated in both kiosk and Internet/intranet formats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPENDENCE
PHARMACOLOGICAL
TREATMENT
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MARIJUANA
Principal Investigator & Institution: Haney, Margaret; Assistant Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001 Summary: There is recent evidence that marijuana use has increased, and that a subset of marijuana smokers are seeking treatment for their marijuana abuse. These data, in combination with empirical evidence that marijuana dependence develops in humans, support the objective of this proposal to develop a model to assess the ability of pharmacological interventions to decrease marijuana use. Specifically, the acute and residual effects of smoked marijuana under both an active and placebo dose of study medication will be assessed. The underlying assumption of this proposal is that marijuana self-administration can be disrupted via several mechanisms. The following behaviors will be measured: marijuana self- administration, psychomotor task performance, social behavior, food intake, and subjective reports of drug effects. Aim #1. Evaluate the ability of the anticonvulsant, divalproex, and the antidepressant, bupropion to decrease marijuana use indirectly by attenuating symptoms of smoked marijuana withdrawal. Hypotheses: these medications will I) attenuate symptoms of irritability, anxiety, and depression during marijuana abstinence, and 2) correspondingly, reduce marijuana self-administration after a period of monitored marijuana abstinence. Aim #2. Evaluate the ability of the mu-opioid antagonist, naltrexone to directly decrease marijuana self-administration by decreasing its acute effects. Hypotheses: naltrexone will 1) decrease the subjective and behavioral effects of smoked marijuana, 2) decrease marijuana self- administration, and 3) decrease the development of marijuana dependence, evidenced by fewer symptoms of abstinence. Thus, naltrexone may be a useful treatment medication in two ways: by decreasing both marijuana smoking and the development of marijuana dependence. Although smoked marijuana is one of the most widely abused drugs in the world, little is known about effective treatments for marijuana abuse and dependence. The strength of this protocol lies in the utilization of a controlled laboratory setting to examine the interactive effects of potential treatment medications with marijuana self-administration and a range of its behavioral effects. The data collected will suggest more efficacious approaches to treating marijuana abusers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOTHERAPY FOR OPIOID AND COCAINE DEPENDENCE Principal Investigator & Institution: Kosten, Thomas R.; Professor of Psychiatry; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-AUG-1988; Project End 31-MAY-2006 Summary: This competitive renewal is a 24-week placebo controlled randomized clinical trial that builds on our demonstration of a significant synergism between contingency management (CM) and the antidepressant desipramine (DMI) in reducing cocaine use in an opioid-maintained population. In that study those who got CMplusDMI went from 9 percent (week 1) to 74 percent (week 12) drug-free urines, while the other three groups (CMplusplacebo, voucher control-VCplusDMI, Vcplusplacebo) rose only to 39 percent in week 12. Two related studies have shown that giving CM alone to these types of patients with depression is particularly ineffective, while a related antidepressant withnoradrenergic activity-bupropion is particularly effective for depression in these patients. Bupropion (300 mg daily) also will improve on DMI by its dopamine
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transporter (DAT) binding that can reverse chronic cocaine induced upregulation of DAT, an activity that DMI does not share. Thus, the proposed study aims to enhance the pharmacotherapy by changing to bupropion and to enhance the CM by reinforcing protreatment behaviors as well as drug-free urines. During the first 12 weeks the CM will be applied towards two goals: 1. drug free urine toxicologies with an escalating schedule of reinforcements for sustained abstinence, 2. behavioral changes to promote continued abstinence. This second goal will be continued during weeks 13-24, while direct reinforcement for urine toxicology results will be discontinued. In summary we address five Specific Aims in 160 methadone maintained patients using a two by two research design that will randomize to four cells: CMplusplacebo, CMplusbupropion, voucher control (VC) plus placebo or VC plus bupropion. 1. To compare bupropion to placebo on treatment retention and cocaine and opioid abstinence. 2. To compare contingency management (CM) to yoked controls on treatment retention and cocaine and opioid abstinence. 3. To examine a potential interaction of bupropion with CM for improving initial abstinence during weeks 1-12 of this trial and in relapse prevention as well as initial abstinence during weeks 13-24. 4. To examine depression as a predictor of response. 5. To examine three month follow-up status after completing the treatment trial for continuation in treatment, abstinence from illicit drugs, and depressive symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT STUDY--BUPROPION HCL AND PLACEBO TREATMENT OF SMOKING IN SCHIZOPHRENICS Principal Investigator & Institution: Fatemi, S Hossein.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001 Summary: Schizophrenia is a debilitating and chronic brain disorder which affects 1% of the world population. There is significant evidence to indicate high rates of smoking in this patient population causing additional health problems for this group of individuals. There is a scarcity of studies examining the effects of psychopharmacologic interventions in helping schizophrenic patients to either reduce or stop their tobacco intake. Recent evidence shows superiority of bupropion HCl to placebo in cigarette smoking cessation. Although cessation of smoking should be the ultimate goal, many schizophrenics are unwilling or unable to quit. We would like to test the hypothesis that bupropion will cause reductions in nicotine use by schizophrenic patients. We propose to do a double blind randomized placebo-controlled within subject cross-over study in 10 subjects to establish the feasibility and acceptability of bupropion in this population. We hope that this study will provide pilot data to undertake a subsequent larger, clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT--EARLY INTERVENTION Principal Investigator & Institution: Lloyd, Elizabeth; Miriam Hospital Providence, RI 02906 Timing: Fiscal Year 2001 Summary: (Applicant's Description) Estimates of smoking prevalence indicate increasing smoking rates among youth. In contrast, little is known about smoking rates among college students, a group that has previously been, but no longer appears to be, more resistant to cigarette use than other young adults. Further, technical college
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students smoke at higher rates than both traditional four-year college students as well as the general population. Given their particular constellation of risk factors, technical college students may be particularly prone to years of continued smoking. Targeting young adults would provide an unexplored window of opportunity for halting the entrenchment of smoking and preventing future detrimental medical, psychological, and economic consequences. The proposed pilot study will test the hypothesis that adding sustained- release bupropion to standard cognitive-behavioral group therapy plus nicotine replacement will enhance the achievement and maintenance of smoking cessation in a sample of young adults (ages 18-30 years) attending technical school. We will also explore the relationship between various risk factors, including sociodemographic and smoking-related variables and psychiatric comorbidity, and smoking cessation outcomes. The study employs a randomized, double-blind, placebocontrolled design to test the incremental efficacy of 1) standard smoking cessation treatment + placebo ,s. z) standard smoking cessation treatment + bupropion hydrochloride. Two hundred smokers will receive 6 group sessions of standard smoking cessation treatment, which includes 7 weeks of transdermal nicotine replacement. Half will receive active bupropion or a matching placebo. Subjects will be treated for 10 weeks and followed for 6 months. Current and past psychiatric symptoms will be assessed. We expect that this study will result in the development of an efficacious treatment for a high-risk young adult population, and will therefore have important clinical and public health significance in reducing prevalence of smoking in future generations. We further expect that this study will increase our knowledge of the interaction of combined pharmacologic and psychosocial treatments on various risk factors for smoking relapse in the process of smoking cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF CIGARETTE SMOKING IN ADHD YOUTH Principal Investigator & Institution: Biederman, Joseph; Chief; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2002 Summary: (Applicant's Description) There is no doubt that cigarette smoking is a substantial source of morbidity and premature morbidity the United States. Each year, cigarette smoking causes about 30 to 40 percent of coronary heart disease deaths and 30 percent of cancer deaths, leading to nearly half a million deaths each year. Yet, despite these statistics, there are more than 54 million smokers in the nation. Four million of these are adolescents and over 3,000 youth start smoking each day. If these rates of teenage smoking continue, the costs to society will be enormous. Cigarette smoking has become so widespread in youth that it is considered a "pediatric disease" by the Food and Drug Administration. Studies suggest that most adults could be prevented from becoming tobacco users if they could be kept tobacco-free during adolescence. This finding suggests that preventive efforts focus on adolescence, a known risk period for the initiation of smoking. This proposal seeks to apply a psychopharmacologic high risk paradigm to prevent regular smoking and nicotine dependence in adolescence. The work has three innovative features: 1) use of epidemiologic data to define a group of adolescents at high risk for smoking; 2) use of an anti-smoking medication that also addresses clinical features of the high-risk group and 3) implementation of procedure to facilitate the long-term follow-up of research participants. These features are defined by the three main aims of our proposal. Prior work shows that children with attention deficit hyperactivity disorder (ADHD), who also have comorbid conduct, mood or anxiety disorders, are at high risk for regular smoking and nicotine dependence. Thus,
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our first aim is to recruit a group of these adolescents into a preventative treatment protocol, before they have initiated regular smoking. Our second aim is to complete a double-blind clinical trial of bupropion for the prevention of smoking in high-risk ADHD adolescents. Bupropion is an appropriate agent for this group for several reasons. It is efficacious for the treatment of depression, one of the most common comorbid disorders in the high risk group. Moreover, prior research also shows that it reduces ADHD symptoms and is an effective treatment for smoking cessation. Moreover, its putative mechanism of action affects neural systems believed to mediate both ADHD and smoking. In addition to these main aims, we will assess the effects of bupropion on symptoms of ADHD and depression and will implement procedures that will allow us to study the outcome of this sample in future proposals, should that be warranted. We will use a balanced, double-blind, placebo-controlled study design. Sixty-five high risk adolescents will be given placebo and sixty-five bupropion. Subjects will he recruited over a 3-month period and will have varying lengths of follow-up based on when they were recruited into the study. The study is designed so that each subject will have at least one year of follow-up data. Some subjects will have as much as 3.5 years of follow-up data. The use of pharmacological agents, such as Bupropion, have not been explored in the prevention of cigarette smoking. Since this medication has been used for both the treatment of ADHD and cigarette smoking, it could aid in the prevention of cigarette smoking in this high-risk population. The number of cases that could he prevented is not trivial. Since there are estimated to be 3.5 million children with ADHD and 20% have been shown to be smokers, targeting this group could potentially impact 700,000 children and adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PSYCHOBIOLOGICAL /GENETIC DETERMINANTS-SMOKING CESSATION Principal Investigator & Institution: David, Sean P.; Memorial Hospital of Rhode Island 111 Brewster St Pawtucket, RI 02860 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): My career goal is to develop the experience, skills, and infrastructure to become an independent investigator in smoking cessation research with a focus on molecular genetics. This K08 Mentored Clinical Scientist Award proposal outlines a comprehensive, five-year program of supervised research in pharmacogenetic smoking cessation clinical trials with Sponsors Raymond Niaura, Ph.D. at Brown University, and Co-Sponsor Peter Shields, M.D. at Georgetown University, a structured didactic seminar series integrated with the Transdisciplinary Tobacco Use Research Center at Brown University combined with laboratory training in genotyping techniques at Georgetown University and establishment of an independent laboratory at Brown University. This work will be informed by an outstanding network of transdisciplinary mentors and collaborative research with Co-Sponsors at the University of Oxford. The focus of the proposed research is an evaluation of the role of the dopamine transporter SLC6A3 polymorphism, and other dopaminergic candidate gene polymorphisms, in treatment response of smokers to bupropion hydrochloride for smoking cessation. The proposed research would be the first study to explore how genotype and treatment interact through multiple cognitive, behavioral, affective, and physiological endophenotypes to reduce the reinforcing properties of smoking and impact smoking outcomes. The specific aims are: (1) To evaluate the role of the dopamine transporter SLC6A3 polymorphism in treatment response to bupropion for smoking cessation, (2) To test the hypotheses that bupropion diminishes the reinforcing
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properties of smoking and that the effect of bupropion on reduction of the reinforcing properties of smoking will be significantly greater among smokers who carry DRD2Taq1 A2/A2 genotypes than it is among smokers with DRD2-Taq1 A1/A1 or A1/A2 genotypes, (3) To investigate the interaction between genotype and cue reactivity among smokers with DRD2-Taq1 A2/A2 and DRD2-Taq1 A1/A1 or A1/A2 genotypes, and (4) To evaluate the impact of additional dopaminergic candidate gene polymorphisms on treatment response to bupropion for smoking cessation and multiple endophenotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PSYCHOPHARMACOLOGY OF ADOLESCENTS WITH AUD AND ADHD Principal Investigator & Institution: Bukstein, Oscar G.; Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: APPLICANT'S ABSTRACT: This proposal for a Mid-Career Investigator Award in Patient-Oriented Research (K-24) describes a plan in patient-oriented research, mentor ship and career development in the area of clinical trials involving adolescents with alcohol use disorders (AUDS) and comorbid attention-deficit hyperactivity disorder (ADHD) and other psychopathology. The mentor ship plan includes organized, structured efforts in recruiting appropriate trainees, including child and adolescent psychiatrists, for mentor ship and involvement and development of specific training experiences for these trainees. The proposed career development plan includes course work and supervision in methodology and statistics related to clinical trials and psychopharmacology in adolescents with ADHD and AUDS. To assist both career development and mentor ship efforts, this application includes a proposal for a doubleblind, placebo-controlled study of bupropion Sustained Release (SR) in adolescents with comorbid AUD and ADHD. The specific aim of the study is to compare the efficacy of bupropion SR vs. placebo in the treatment of adolescents with comorbid AUD and ADHD for ADHD symptoms, drinking and other substance use behaviors. There have been few studies that have examined pharmacological treatment in this comorbid population. As psycho stimulants present a potential risk to adolescents with comorbid AUD/ADHD due to abuse or diversion, other medications need to be considered. One hundred (100) adolescents, ages 14-18, will be recruited from community treatment programs. After screening, informed consent and baseline assessment to confirm diagnoses of an AUD and current ADHD, the adolescents will be randomized into two groups, which will receive either placebo or bupropion SR (titrated to a dose of 300 mg/day). During the 16-week trial, weekly or bi-weekly follow-up assessments will assess efficacy for both ADHD and AUD symptomatology and safety. The results and conduct of this study, along with organized, structured mentor ship activities and the development of advanced skills in clinical trials, will serve to advance the applicant's long-term goals of conducting both pharmacological and multi-modal clinical trials in adolescents with AUDs or Substance Use Disorders (SUDS) and comorbid psychiatric disorders. It will also provide opportunities for mentor ship to trainees and junior colleagues. These complementary efforts will advance the field through both research and training. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RETARGETING MID LIFE AND OLDER SMOKERS Principal Investigator & Institution: Ossip-Klein, Deborah J.; Research Associate Professor; Community and Prev Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001; Project Start 03-JUL-1996; Project End 30-JUN-2004 Summary: (Applicant's abstract): There are over 13 million smokers ages 50+ in the United States, who tend to be heavy, long-term smokers who are more likely to have chronic diseases caused or exacerbated by smoking. Stopping smoking can reduce morbidity and mortality from disabling diseases and conditions across the lifespan. Thus, the implications of smoking and smoking cessation for maintenance of health and independent living for older populations are considerable. Little data are available on effective treatments for smoking in this growing population. Assisted self-help interventions seem particularly appropriate to this group, who may be limited geographically or by health status in their ability to access smoking intervention services. Preliminary results from the current and preceding trials suggest that proactive telecounseling, in combination with a self-help manual and access to a reactive quitline, enhances quit rates, particularly among those using concurrent pharmacotherapy for smoking cessation. Results of other trials indicate that multiple quit attempts are often necessary to achieve smoking abstinence, and telecounseling may enhance recycling (i.e., re-quitting after a failed attempt). The proposed study will extend the scope of the current trial to examine the effectiveness of recycling smokers ages 50+ with a failed quit attempt in the past two years (recruited from the current trial and supplemented with community recruits). Two groups will be compared: 1) Minimal Intervention Control self-help manual and access to a reactive quitline (smokers call in to the quitline for assistance); and 2) Proactive - manual and quitline along with proactive telecounseling calls (calls out to participants) to supporting re-quitting and supporting use of FDA approved pharmacotherapies for smoking cessation (nicotine replacement, bupropion, and others if they are approved during the period of study. Subjects will be followed at 6, 12, and 18 months for assessment of smoking status, health outcomes, and use of cessation resources (manual, quitline, proactive telecounseling, pharmacotherapy) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SERIAL CSF SAMPLING DURING TRYPTOPHAN DEPLETION BIOPOLAR DEPRESSED PATIENTS Principal Investigator & Institution: Gwirtsman, Harry E.; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001 Summary: To compare between groups, and correlate within subjects, the changes in 49 hour lumbar CSF levels of indoleamines and changes in mood behaviors with a depletion of plasma tryptophan (TRP, the precursor of serotonin, 5HT) in twelve bipolar depressesed patients. Within subject comparisons are planned between a baseline TRP depleted state prior to treatment and a TRP depleted state during antidepressant line treatment. Additional comparisons will be analyzed between previously studied normals and other psychopathologic groups. This will compare sertraline and bupropion effects on central indoleamine metabolism and mood. CSF levels of the antidepressants at steady state will be compared to plasma levels. CSF levels of indoleamines at baseline will correlate with mood improvement after treatment. The primary objectives will generalize to other indoleamines. Shifts in ratios between CSF
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levels of various indoleamines during different phases of TRP depletion will provide information regarding chronic effects of sertraline on indoleamine metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP/DOPAMINE PHENOTYPES IN GENETICALLY DISTINCT MICE Principal Investigator & Institution: Rye, David B.; Associate Professor; Neurology; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2003 Summary: (adapted from the applicants' absract) One poorly understood neuromodulator of state is the mesostriatal dopamine (DA) system, which not only promotes motivation/reward and movement, but also arousal (viz., wakefulness). Conversely, DA blockade and interruption of mesostriatal pathways slows movement and promotes sleepiness. The details of mesostriatal DA's effects upon wake/sleep rhythms, and sleep architecture, and the cellular and subcellular substrates involved remain poorly defined. Circadian and homeostatic wake/sleep factors affect mesostriatal circuit plasticity, but their functional import is also undefined. Mice with genetic deletions of the dopamine transporter (DAT-/-), their heterozygotes (DAT+/-), wild type littermates, the pure C57BL/6 and S129/sv strains from which the transgenics derive, and the DBA/2 inbred strain with known under expression of mesostriatal D2 receptors afford a means to probe DA's role in state control, and to account for genetic variation in wake/sleep phenotypes. Aim #1 proposes to characterize 24-hour motor activity patterns in relation to sleep/wake architecture in these mice. Motor hyperactivity in DAT -/- and DAT +/- during the subjective night yields to hypoactivity during subjective day suggesting a sleep/wake reversal in the face of chronically elevated synaptic DA (preliminary data). The mechanisms underlying a homeostatic sleep drive powerful enough to overcome chronic DA elevations - if indeed sleep attends the observed hypoactivity - may reside in other proteins involved in mesostriatal DA transmission. Aim #2 therefore proposes to measure traditional DA markers, and molecularly defined D1 receptor, DAT and vesicular monoamine transporter (vMAT2) expression across 24-hours in limbic and motor striatal circuits to enhance interpretation of Aim #1 findings. Aim #3 investigates the effects of prolonged wakefulness induced by physical means, bupropion (a DAT blocker), and caffeine (an adenosine receptor blocker), on the mesostriatal DA system in these same mice. The investigators postulate that these transgenic and inbred mice will exhibit unique circadian rhythms of proteins mediating DA neurotransmission and unique responses of these proteins to prolonged wakefulness that may be treatment modality specific, much the same way that depressives differ in their response to REM-sleep deprivation, and narcoleptics differ from depressives in their REM-sleep responses to DAT blockade. Taken together, the findings will advance an understanding of how state might modulate the course and treatment of insomnia, depression, and neuropsychiatric diseases whose pathophysiologies are rooted in DA sensitive basal ganglia circuits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SMOKING CESSATION FOR HEAD AND NECK CANCER PATIENTS Principal Investigator & Institution: Schnoll, Robert A.; Associate Member; Fox Chase Cancer Center Philadelphia, PA 19111 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007
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Bupropion
Summary: (provided by applicant): Continued smoking by head and neck cancer patients is associated with poor survival, a greater risk of disease recurrence and a second primary tumor, reduced treatment efficacy, and adverse treatment-related complications. Nevertheless, 25-35 percent of patients who smoked prior to the diagnosis continue to do so following treatment. To date, rigorous studies of smoking cessation interventions for cancer patients have yet to be conducted. Since the presence of significant depressive symptoms - which can impede successful quitting - are common among cancer patients, it may be particularly important to address negative affect within a cessation program for this population using an antidepressant (i.e., bupropion). However, in light of barriers to bupropion use, including cost and adverse side effects, discerning subgroups of smokers in need of intensive (i.e., use of pharmacologic treatments, in addition to counseling and nicotine replacement therapy [NRT]) vs. moderate (i.e., involving counseling and NRT alone) treatments has become a priority in the field of nicotine addiction research. The presence vs. the absence of significant depressive symptoms may be a useful way for matching smokers to optimal treatments (i.e., depressed smokers may require bupropion in addition to counseling and NRT, whereas non-depressed smokers may be able to achieve cessation with NRT and counseling alone). Further, the mechanism through which bupropion affects smoking behavior has yet to be clearly delineated, although it may be through bupropion's influence on affect. Thus, this placebo-controlled randomized trial with 366 head and neck cancer patients will: 1) Compare intensive smoking cessation treatment (i.e., bupropion, NRT, counseling) to moderate smoking cessation treatment (i.e., placebo, NRT, counseling) for increasing quit rates among head and neck cancer patients (Aim 1);2) Determine whether the presence of significant depressive symptoms moderate the effect of bupropion on quit rates (Aim 2); and 3) Explore whether the effect of bupropion on smoking cessation is mediated by changes in positive or negative affect (Aim 3). The primary outcome for this study will be continuous abstinence, assessed using the time-line follow-back method, from the quit day until the 2-, 6-, and 12-month follow-up assessments. Overall, data from this study may guide the use of bupropion for treating nicotine addiction among head and neck cancer patients. In particular, our results may provide a guide for matching intensive vs. moderate cessation interventions according to the psychological needs of the cancer patient. Further, understanding the role of changes in affect as the mechanism that underlies the effects of bupropion may help to refine mood management clinical approaches for cancer patients. In turn, our findings may help guide the implementation of smoking cessation treatments for all cancer patients within Comprehensive Cancer Centers in the US. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRESS RESPONSE AND SMOKING CESSATION IN DEPRESSED YOUTH Principal Investigator & Institution: Rao, Uma; Associate Professor; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Cigarette smoking and other forms of tobacco exposure are the leading preventable causes of morbidity and mortality in our society, Epidemiological surveys have shown that over 90% of people who ever smoked and 70% of regular smokers initiated smoking before the age of 18. Research also indicates that early initiation of smoking may lead to more severe form of nicotine dependence and reduced likelihood of quitting smoking in later life. Therefore, smoking during
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adolescence not only relates to the younger population, but also to the long-term physical and mental health of adults. Given the socioeconomic and psychosocial burden associated with adolescent smoking, early and effective intervention is critical. Despite the evidence that nicotine addiction begins during adolescence, little work has been done on developing interventions. Using a randomized, double-blind, placebocontrolled design, this investigation seeks to evaluate whether bupropion, an antidepressant drug that is also effective for smoking cessation in adults, is helpful in reducing smoking in depressed adolescents. In addition to examining the short-term effect of bupropion on smoking cessation, bupropion's effect on smoking cessation status and clinical course of depression will be evaluated at 6 months. The study also aims to examine the relationship between hypothalamic-pituitary-adrenal (HPA) activity and smoking cessation in response to short-term treatment with bupropion in this population. To our knowledge, this proposal represents the first investigation to examine the role of pharmacotherapy for cigarette smoking in depressed youngsters. By including depressed adolescents, the study will focus on a group known to be at high risk for smoking. Data also suggest that adult depressed patients may be more treatment-resistant to smoking cessation interventions. The study also aims to identify subgroups of depressed adolescents with differential response to bupropion. Such information potentially would be helpful in the development and testing of more specific treatments for the different groups of adolescent smokers. More focused and effective interventions early in the course of the disorder might be helpful in potentially reducing the long-term morbidity and mortality stemming from teenage smoking. Results of the proposed study might lead to treatment for both depression and nicotine dependence in adolescent patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNTHESIS OF NICOTINE ANALOGS Principal Investigator & Institution: Glennon, Richard; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 30-JUN-2006 Summary: Because nicotine seems to produce a number of beneficial effects, presumably mediated via nicotinic acetylcholinergic (nACh( receptors, it is desirable to develop novel nicotinic agents that retain the beneficial effects of nicotine but that lack its toxic and undesirable aspects. Such agents could be of benefit in smoking cessation therapy, pain management, and the treatment of certain mental and neurological disorders. Our long term goal is the development of such agents. A more immediate goal is an enhanced understanding of neuronal nACh receptors and knowledge of how to design agents that will interact selectively with these receptors. To this end, we are attempting to define and investigate and pharmacophore for central nACh receptor action. A nicotinic pharmacophore, initially proposed in 1970, has been challenged and modified by us and by others. We currently believe that multiple pharmacophores are possible, and that different pharmacophores might even account for agonist vs. antagonist actions. Our present investigations can be broadly divided into two categories: development and validation of pharmacophore models, and exploitation of leads we have already developed. Specifically, we propose to a) explore what appears to be a new nACh receptor binding feature, b) evaluate a structure-based hypotheses regarding binding and functional activity, c) determiner whether or not structurally distinct ligands bind in a common manner at nACh receptors, d) investigate a series of agents that offers the prospect of possessing "peripheral" analgesic activity, e) explore potentially selective nACh receptor ligands, and f) investigate the actions of bupropion
52
Bupropion
optical isomers and metabolites, and to examine a role for dopamine in the nicotine-like effects of bupropion. Compounds necessary for these investigations will be synthesized. All compounds will be examined in radioligand binding assays at alpha4beta2, nACh receptors. Selected compounds, depending on their affinity (i.e., alpha4beta2 Ki 100 nM), will be examined in other binding assays and as agonists and antagonists in functional assays (e.g. antinociceptive activity, locomotor effects and body temperature using mice; drug discrimination studies with rats), following a specific protocols. Radioligand binding (and to some extent functional) data will be used to determine the validity of existing pharmacophore models and, if necessary to develop new models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRAFFICKING TRANSPORTERS
AND
REGULATION
OF
MONOAMINE
Principal Investigator & Institution: Melikian, Haley E.; Assistant Professor; Psychiatry; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007 Summary: (provided by applicant): Monoamine reuptake is a major mechanism for regulating extraneuronal monoamine levels and terminating synaptic transmission. Reuptake is mediated by plasma membrane transporters that are the primary targets for psychostimulants such as cocaine, methamphetamine and MDMA ("Ecstasy"), as well as for therapeutic drugs such as fluoxetine (Prozac), sibutramine (Meridia), bupropion (Wellbutrin) and methylphenidate (Ritalin). These agents block reuptake, resulting in elevated extraneuronal monoamine levels and enhanced postsynaptic responses. Recent evidence demonstrates that transporters are subject to acute regulation by cellular signaling pathways. Transporter regulation is coupled to dynamic changes in transporter cell-surface presentation, suggesting that membrane trafficking is fundamental to transporter homeostasis and regulation. However, the cellular and molecular mechanisms governing transporter regulation and trafficking are not yet defined. Given the pronounced effect pharmacological transporter blockade exerts on synaptic transmission, it is highly likely that transporter sequestration also has significant downstream effects on neuronal signaling. Moreover, modulation of transporter availability is certain to have significant impact on the efficacy of psychoactive drugs. The major goals of this project are to elucidate the cellular and molecular mechanisms mediating acute transporter regulation and trafficking. This investigative line will be pursued by testing the following hypotheses: (1) Transporters undergo constitutive internalization and recycling, and (2) transporter regulation is achieved by altering transporter trafficking kinetics. These hypotheses are based on strong preliminary data that the dopamine transporter (DAT) undergoes constitutive endosomal trafficking and that protein kinase C (PKC) activation directly alters DAT trafficking. The proposed hypotheses will be tested by directly analyzing basal and regulated transporter trafficking kinetics in cell lines. Intrinsic domains mediating basal and PKC-regulated DAT trafficking will be identified using molecular truncation and mutagenesis approaches. It is expected that these approaches will provide a clear and comprehensive picture of the mechanisms underlying acute transporter modulation. Such results are expected to have a significant impact on future therapeutic strategies aimed at monoamine-related drug abuse and mental illnesses. Moreover, the outcomes will greatly improve our understanding of the factors contributing to monoamine availability and signaling in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSDERMAL CODRUGS FOR TREATMENT OF ALCOHOLISM Principal Investigator & Institution: Stinchcomb, Audra L.; Assistant Professor; Pharmaceutical Sciences; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Naltrexone is currently used in oral tablet form as an adjunct in the treatment of alcohol dependence, as well as to help maintain opioid addicts in a drug-free state. Transdermal delivery of naltrexone is desirable in order to help reduce side effects associated with oral therapy and improve compliance. Naltrexone itself does not have the essential physicochemical properties that would allow a therapeutic dose of the drug to cross the human skin barrier. This problem may be solved by designing and synthesizing derivatives (co-drugs) which are more skin permeable than naltrexone. A co-drug or mutual pro-drug consists of two synergistic drugs chemically linked together, in order to improve the drug delivery properties of one or both drugs. Bupropion, a successful smoking cessation treatment, is the drug chosen for linkage to naltrexone. Simultaneous treatment of alcohol and tobacco addiction is vital, because of the biochemical and behavioral causal links in this common co-morbidity, as well as alcoholics' high death rate from tobacco-related diseases. Opioid addicts may also benefit from this treatment combination, because of their high prevalence of smoking and co-abuse. The hypothesis is that chemical combinations of naltrexone and bupropion in a co-drug form will improve the transderrnal delivery rate of the drugs. The specific aims of this project are: (1) to synthesize a series of naltrexone, 6-beta-naltrexol, bupropion, and hydroxybupropion codrugs designed to elucidate quantitative structure-activity relationships (QSARS) for transdermal flux and subsequent bioconversion rates, (2) to characterize the physicochemical properties of the co-drugs, including molecular volume, lipophilicity, hydrogen-bonding potentials, melting points, heats of fusion, hydrolysis kinetics, and solubilities in select solvents, (3) to measure the co-drugs' penetration and bioconversion rates in human skin in vitro, and (4) to characterize the pharmacokinetics of the co-drugs in guinea pigs in vivo. These objectives will help to identify the critical parameters involved in the optimization of transdermal co-drug designs. Correlation of the in vitro data with the in vivo model will aid in the creation of a reliable QSAR database that is necessary to help identify the best co-drugs for clinical use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSDERMAL SCHIZOPHRENICS
NICOTINE
AND
BUPROPION-SR
IN
Principal Investigator & Institution: Tidey, Jennifer W.; Ctr for Alcohol & Addict Studs; Brown University Providence, RI 02912 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant) There is a high prevalence (60-88 percent) of cigarette smoking among people with schizophrenia, but few smoking cessation interventions have been developed for these patients. Little is known about factors that control smoking in this population or whether interventions that reduce cigarette smoking among the general population are effective in smokers with schizophrenia. Two pharmacotherapies that reduce smoking in the general population are transdermal nicotine and sustained release bupropion. Because of neurochemical dysfunction associated with schizophrenia, these pharmacotherapies may be less effective in smokers with schizophrenia. Clinical and experimental studies on the effects of nicotine replacement in smokers with schizophrenia have yielded equivocal results. Preliminary
54
Bupropion
results from a single treatment study with sustained release bupropion appear promising. The studies in the present proposal are designed to examine under controlled laboratory conditions the effects of transdermal nicotine (0, 21, 42 mg/day) and sustained release bupropion (0, 150, 300 mg/day) on smoking in people with schizophrenia and non-schizophrenic controls. The effects of transdermal nicotine and sustained release bupropion on smoking topography measures, smoking urges, nicotine withdrawal symptoms and affect will be determined. These studies use within-subjects, repeated measures, placebo controlled designs. Together, they will provide muchneeded information on the biological, behavioral and subjective effects of transdermal nicotine and sustained release bupropion on smoking in people with schizophrenia. In turn, this information could contribute to the development of effective smoking cessation treatments for smokers with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF ADULT ADHD IN METHADONE PATIENTS 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 2001; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: In spite of the availability of effective pharmacologic agents for the treatment of opiate dependence, such as methadone and naltrexone, successful treatment remains inadequate for many patients. One factor which may contribute to poor treatment outcome for patients in methadone maintenance programs is the presence of comorbid disorders, of which Attention-Deficit Hyperactivity Disorder (ADHD) has been a neglected one. Based on data we have collected, the prevalence of adult ADHD is substantially higher among substance abusers, both methadone-maintained patients and cocaine abusers seeking treatment, compared to the general population. It is our hypothesis that a comorbid diagnosis of ADHD in methadone-maintained patients may impede treatment efficacy. Medications, such as methylphenidate (MPH) and bupropion (BRP), are currently two of the most effective treatments for ADHD. In fact, we have shown that sustained-release MPH is effective in reducing both ADHD symptoms and cocaine use in cocaine abusers with adult ADHD. By treating methadone maintained patients who have adult ADHD with effective medications, we hypothesize that a reduction in ADHD symptoms will improve treatment efficacy as defined by: retention in the treatment study and in the methadone program, reduction in illicit drug use and drug craving, and improvement in functioning based on the Addiction Severity Index and Clinical Global Impression. Specifically, the effectiveness of sustained-release MPH and sustained-release BPR will be assessed using a three-armed, double-blind, placebo-controlled treatment trial in 120 methadone-maintained patients diagnosed with adult ADHD. Unfortunately, ADHD often goes undiagnosed. The second aim of this proposal is to determine the positive predictive value of several self-report instruments used to evaluate adult ADHD. Specifically, we will determine the utility of these instruments for assessing adult ADHD in substance-abusing populations. Overall, this proposal will provide a better understanding of the relationship between ADHD and substance abuse, better diagnostic evaluation, and improved pharmacologic treatment approaches for this sub-population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TREATMENT OF NICOTINE DEPENDENCE IN AN HMO SETTING Principal Investigator & Institution: Swan, Gary E.; Director; Sri International 333 Ravenswood Ave Menlo Park, CA 94025
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55
Timing: Fiscal Year 2002; Project Start 03-JAN-1997; Project End 30-SEP-2004 Summary: In the grant CA71358, Treatment of Nicotine Dependence in and HMO Setting, we conducted a large randomized field trial of the effectiveness of two different doses of bupropion SR (150mg or 300mg) in combination with two different approaches to behavioral support (the Zyban Advantage Plan (ZAP), a personalized mailing program or Free & Clear, a proactive telephone-based smoking cessation program). The trial, conducted at Group Health Cooperative (GHC), showed that the higher dose was associated with short-term outcome (similar to the one industry-sponsored trial of different dosing levels) but that higher intensity behavioral counseling was associated with long-term effectiveness. The trial was limited to patients enrolled in the staff model system at GHC and did not include patients under the care of physicians in the GHC "network" - community doctors, group practices, and other hospitals contracted with GHC. In this application we seek to disseminate to 500-700 "networked" providers within GHC Northwest District three main study findings: 1) that a relatively standalone recruitment and screening system with physician back-up can result in safe and effective treatment of their smoking patients; 2) that a higher dose of bupropion SR was effective in the short run but more so in combination with the moderately intensive Free & Clear program and that even the lower dose of buproprion SR in combination with Free & Clear program can result in satisfactory outcomes at 12 months; and 3) that encouraging concomitant use of a behavioral support program is a more effective addition to a course of bupropion SR than simply using a higher dose. As part of this dissemination effort we aim to: 1) provide feedback to the targeted populations from the original trial (smokers, GHC staff model physicians); and 2) disseminate the findings from the trial to GHC-contracted physicians and health care providers who were not actively informed while it was being conducted (the "network" physicians) by: a) utilizing components of the Precede-Proceed Model of Health Promotion Planning to devise, in collaboration with the intended audience, an approach to dissemination of the trial's findings and methods that will maximize use of available GHC resources; b) utilizing the theoretical framework provided by Moulding, Silagy and Weller for designing effective dissemination practices; and c) assessing process and outcome measures including elements of the RE-AIM model of Glasgow, Vogt, and Boles to evaluate the dissemination effort. Effective dissemination of the trial's findings will result in greater utilization of behavioral counseling and possibly lower dosages of bupropion SR in the treatment of smokers at GHC. Thus, more efficient use of existing resources will result in greater reach of cessation efforts to smoking patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF NICOTINE DEPENDENT SMOKERS Principal Investigator & Institution: Hayes, Steven C.; Chair and Foundation Professor; Psychology; University of Nevada Reno Reno, NV 89557 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Certain nicotine-dependent smokers smoke in order to modify or suppress unpleasant states such as negative affect and nicotine withdrawal. For these smokers, the immediate avoidance of troublesome thoughts, feelings, or sensations appears to take precedence over the known health risks associated with smoking. This proposal suggests a treatment model for nicotine-dependent smokers derived from the experimental literature on suppression, acceptance, and social support. This biobehavioral model is applied to the hypothesized mechanism of action in slow release bupropion, a promising new treatment for smoking cessation. A psychosocial component using social support to facilitate acceptance skills training for nicotine-
56
Bupropion
dependent smokers is proposed. It is hypothesized that acceptance, suppression, and insession social support may mediate treatment effects and moderate the impact of withdrawal symptoms and negative affect on treatment outcome. The specific aims are (a) to use the Experiential Acceptance and Support model to generate a manual integrating relevant interventions from Acceptance and Commitment Therapy and Functional Analytic Psychotherapy, to be used as a psychosocial component in the treatment of nicotine-dependent smokers, (b) to investigate theory-specified variables that may reflect on the putative mechanisms underlying the proposed treatment and slow release bupropion, (c) to pilot the combined treatment, (d) to evaluate the role of withdrawal symptoms and negative affect on treatment process and outcome, (d) to evaluate the clinical acceptability of the proposed treatment, and (e) to generate data to use in a power analysis for future studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENTS MECHANISMS
FOR
NICOTINE
DEPENDENCE:
BRAIN
Principal Investigator & Institution: Brody, Arthur L.; Associate Professor - in Residence; Brentwood Biomedical Research Institute Bldg. 114, Room 218 Los Angeles, CA 90073 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Despite new medication options for nicotine dependence, abstinence rates after 6 months or more of treatment remain relatively low at 14 to 35.5%. Because severity of craving has repeatedly been linked with relapse in smokers attempting abstinence, a possible route to the development of more effective treatments for nicotine dependence is through a better understanding of the neurobiological substrates of current successful treatments that reduce craving and cigarette usage. Recent brain imaging work from our group demonstrates that exposure of heavy cigarette smokers to cigarette related (compared with neutral) cues results in increases in both the intensity of craving and normalized metabolism in the anterior cingulate gyrus spanning the midline and left posterior orbitofrontal cortex. Additionally, intensity of cigarette craving was significantly positively correlated with relative metabolism in the bilateral OFC, dorsolateral prefrontal cortex, anterior insula, and right somatosensory cortex. These findings are consistent with studies of craving for other drugs that produce dependence (cocaine, opiates, and alcohol). In this proposal, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) will be used to assess regional brain metabolism associated with cigarette craving both before and after two distinct forms of treatment for nicotine dependence in order to examine the brain mechanisms of these treatments. Subjects meeting full DSM-IV criteria for nicotine dependence will undergo 2 FDG-PET scans (one during exposure to cigarette-related cues and the other during exposure to neutral cues) both before and after treatment with either bupropion HCI with no concomitant counseling, structured practical group counseling (using relapse prevention techniques) with no concomitant medication, or pill placebo. The goals of this study are: (1) to determine changes in regional cerebral metabolic activation during presentation of cigarette-related cues from pre- to posttreatment with either bupropion HCI, practical group counseling, or placebo, (2) to determine changes in cue-induced cigarette craving from pre- to post- treatment with either bupropion HCI, practical group counseling, or placebo, and determine brain metabolic correlates of changes in cue-induced craving, (3) to determine changes in regional metabolism in the neutral state from pre- to post- treatment with either bupropion HCI or practical group counseling and (4) to determine pre- treatment
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regional brain metabolic predictors of response to bupropion HCI and practical group counseling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRIAL OF SERTRALINE AND BUPROPION IN DEPRESSED PATIENTS Principal Investigator & Institution: Gillin, J C.; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TRYPTOPHAN DEPLETION IN BIPOLAR DEPRESSED PATIENTS Principal Investigator & Institution: Salomen, Ronald; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001 Summary: To compare between groups, and correlate within subjects, the changes in 49 hour lumbar CSF levels of indoleamines and changes in mood behaviors with a depletion of plasma tryptophan (TRP, the precursor of serotonin, 5HT) in twelve bipolar depressed patients. Within subject comparisons are planned between a baseline TRP depleted state prior to treatment and a TRP depleted state during antidepressant line treatment. Additional comparisons will be analyzed between previously studied normals and other psychopathologic groups. This will compare sertraline and bupropion effects on central indoleamine metabolism and mood. CSF levels of the antidepressants at steady state will be compared to plasma levels. CSF levels of indoleamines at baseline will correlate with mood improvement after treatment. The primary objectives will generalize to other indoleamines. Shifts in ratios between CSF levels of various indoleamines during different phases of TRP depletion will provide information regarding chronic effects of sertraline on indoleamine metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WEB-BASED SMOKING CESSATION MEDICATION COMPLIANCE SYSTEM Principal Investigator & Institution: Cartter, Christian; Quitnet.Com, Inc. 1 Appleton St, 4Th Fl Boston, MA 02116 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-SEP-2003 Summary: (provided by applicant): The prevalence of smoking among U.S. adults has remained relatively stable for the past five years at approximately 25%. Innovative approaches are needed to reach and treat the population of smokers. Preventive interventions which rely on behavioral counseling and social support, and which have large self-help components are well-suited to delivery via the Internet. Indeed, several recent studies have demonstrated efficacy of preventive health interventions delivered via the Internet. QuitNettm is a commercial website that implements the Tobacco Cessation Guidelines from the Surgeon General and the AHRQ. A key element of these guidelines, now regarded as the standard of care, is the use of pharmacotherapy. In order to have optimal effectiveness, pharmacotherapy requires support in the form of instructions for proper use, adjunct behavioral counseling, and follow-up. The primary threat to the efficacy of pharmacotherapy stems from problems with treatment
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Bupropion
compliance. The goal of this proposal is to develop a Medication Support System (MSS) that maximizes the efficacy of pharmacotherapy by addressing threats to compliance using proven cognitive and behavioral strategies. The MSS will be implemented as part of a comprehensive smoking cessation intervention offered on QuitNet.com and will consist of the following nine inter-related modules: 1) the Withdrawal Module conducts assessment of and intervention around withdrawal symptoms; 2) the Medication Trouble Shooting Module provides information and problem solving for patients experiencing difficulties (e.g., side effects) with medication use; 3) the Incentives and Rewards Module provides rewards contingent on the achievement of small goals and large milestones related to quitting smoking; 4) the Proactive Email Reminder Module generates proactive reminder messages to subscribers regarding medication-related behavioral goals; 5) the Ask the Expert Module provides intra-treatment support and guidance regarding pharmacotherapy through access to our smoking cessation expert; 6) the Bulletin Board Module facilitates the provision of social support among members around pharmacotherapy; 7) the Customized Medication Calendar and Journal encourage subscribers to self-monitor medication use and other smoking behaviors; 8) the Frequently Asked Question Module provides basic information that prepares and educates subscribers about nicotine dependence and its treatment, as well as the expected effects, side-effects, and benefits of pharmacotherapies; 9) the Buddy System Module encourages more intensive 1:1 support between subscribers and facilitates the identification of stage-matched buddies or stage- mismatched mentors. In Phase I, we will develop detailed specifications and conduct programming of all nine modules of the MSS system. A prototype will be presented to potential consumers in two rounds of focus groups to obtain detailed feedback. Current smokers and/or recent ex-smokers (N = 30) who used nicotine replacement and/or bupropion will be invited to participate in Round I focus groups to provide feedback on the MSS design and specifications. Focus group data will be used to finalize design specifications of the MSS system. In Round II focus groups, participants (N = 30) will use a working prototype of the system and provide feedback on usability, system layout and content areas. Feedback obtained in these sessions will be used to finalize development of the MSS system prior to launching on QuitNet. The goal of Phase II is to evaluate the efficacy of the MSS with respect to medication compliance and quitting outcomes in a randomized clinical trial. 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 “bupropion” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for bupropion in the PubMed Central database: 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Adverse events with Zyban (buproprion). by Kolber M, Spooner GR, Szafran O. 2003 Jul 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=164969
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Bupropion (Zyban, Wellbutrin SR): reports of deaths, seizures, serum sickness. by Wooltorton E. 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=99232
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Drug safety without borders: concerns about bupropion. by Mintzes B, Bassett K, Wright JM. 2002 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=121939
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General Practitioners' views on the provision of nicotine replacement therapy and bupropion. by McEwen A, West R, Owen L. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59675
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 bupropion, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “bupropion” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “bupropion” (hyperlinks lead to article summaries): •
A 102-center prospective study of seizure in association with bupropion. Author(s): Johnston JA, Lineberry CG, Ascher JA, Davidson J, Khayrallah MA, Feighner JP, Stark P. Source: The Journal of Clinical Psychiatry. 1991 November; 52(11): 450-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1744061&dopt=Abstract
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A case of bupropion-associated delirium. Author(s): Dager SR, Heritch AJ. Source: The Journal of Clinical Psychiatry. 1990 July; 51(7): 307-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2114399&dopt=Abstract
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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Bupropion
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A case of bupropion-induced seizure. Author(s): Sheehan DV, Welch JB, Fishman SM. Source: The Journal of Nervous and Mental Disease. 1986 August; 174(8): 496-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3090199&dopt=Abstract
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A case of monthly unipolar psychotic depression with suicide attempt by selfburning: selective response to bupropion treatment. Author(s): Schenck CH, Mandell M, Lewis GM. Source: Comprehensive Psychiatry. 1992 September-October; 33(5): 353-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1395556&dopt=Abstract
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A clinical trial of bupropion in the treatment of depressed outpatients. Author(s): Hughes S, Barnett S, Sosnouski P, Kirksey DF. Source: Minn Med. 1984 September; 67(9): 501-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6436657&dopt=Abstract
•
A comparative study of bupropion and amitriptyline in depressed outpatients. Author(s): Mendels J, Amin MM, Chouinard G, Cooper AJ, Miles JE, Remick RA, Saxena B, Secunda SK, Singh AN. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 118-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406439&dopt=Abstract
•
A comparison of bupropion hydrochloride with dexamphetamine and amitriptyline in healthy subjects. Author(s): Peck AW, Bye CE, Clubley M, Henson T, Riddington C. Source: British Journal of Clinical Pharmacology. 1979 May; 7(5): 469-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=475943&dopt=Abstract
•
A comparison of bupropion, dextroamphetamine, and placebo in mixed-substance abusers. Author(s): Miller L, Griffith J. Source: Psychopharmacology. 1983; 80(3): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6412263&dopt=Abstract
•
A comparison of sustained-release bupropion and placebo for smokeless tobacco cessation. Author(s): Glover ED, Glover PN, Sullivan CR, Cerullo CL, Hobbs G. Source: American Journal of Health Behavior. 2002 September-October; 26(5): 386-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206448&dopt=Abstract
Studies
61
•
A comparison of sustained-release bupropion and placebo for smoking cessation. Author(s): Hurt RD, Sachs DP, Glover ED, Offord KP, Johnston JA, Dale LC, Khayrallah MA, Schroeder DR, Glover PN, Sullivan CR, Croghan IT, Sullivan PM. Source: The New England Journal of Medicine. 1997 October 23; 337(17): 1195-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9337378&dopt=Abstract
•
A comparison of the safety and efficacy of bupropion HCL and amitriptyline hcl in depressed outpatients. Author(s): Remick RA, Campos PE, Misri S, Miles JE, Van Wyck Fleet J. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1982; 6(4-6): 523-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6819598&dopt=Abstract
•
A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Author(s): Wilens TE, Spencer TJ, Biederman J, Girard K, Doyle R, Prince J, Polisner D, Solhkhah R, Comeau S, Monuteaux MC, Parekh A. Source: The American Journal of Psychiatry. 2001 February; 158(2): 282-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156812&dopt=Abstract
•
A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. Author(s): Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, Fiore MC, Baker TB. Source: The New England Journal of Medicine. 1999 March 4; 340(9): 685-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10053177&dopt=Abstract
•
A double-blind comparison of bupropion and amitriptyline in depressed inpatients. Author(s): Davidson J, Miller R, Van Wyck Fleet J, Strickland R, Manberg P, Allen S, Parrott R. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 115-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406438&dopt=Abstract
•
A double-blind study comparing idazoxan and bupropion in bipolar depressed patients. Author(s): Grossman F, Potter WZ, Brown EA, Maislin G. Source: Journal of Affective Disorders. 1999 December; 56(2-3): 237-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10701483&dopt=Abstract
62
Bupropion
•
A double-blind study of bupropion and placebo in depression. Author(s): Feighner JP, Meredith CH, Stern WC, Hendrickson G, Miller LL. Source: The American Journal of Psychiatry. 1984 April; 141(4): 525-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6422779&dopt=Abstract
•
A double-blind trial of bupropion in children with attention deficit disorder. Author(s): Casat CD, Pleasants DZ, Van Wyck Fleet J. Source: Psychopharmacology Bulletin. 1987; 23(1): 120-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3110853&dopt=Abstract
•
A double-blind trial of bupropion versus desipramine for bipolar depression. Author(s): Sachs GS, Lafer B, Stoll AL, Banov M, Thibault AB, Tohen M, Rosenbaum JF. Source: The Journal of Clinical Psychiatry. 1994 September; 55(9): 391-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7929019&dopt=Abstract
•
A fixed-dose (300 mg) efficacy study of bupropion and placebo in depressed outpatients. Author(s): Lineberry CG, Johnston JA, Raymond RN, Samara B, Feighner JP, Harto NE, Granacher RP Jr, Weisler RH, Carman JS, Boyer WF. Source: The Journal of Clinical Psychiatry. 1990 May; 51(5): 194-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2110559&dopt=Abstract
•
A high-performance liquid chromatographic method for quantitating bupropion in human plasma or serum. Author(s): Jennison TA, Brown P, Crossett J, Urry FM. Source: Journal of Analytical Toxicology. 1995 March-April; 19(2): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7769789&dopt=Abstract
•
A multicenter evaluation of bupropion versus placebo in hospitalized depressed patients. Author(s): Fabre LF, Brodie HK, Garver D, Zung WW. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 88-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406472&dopt=Abstract
•
A multicenter evaluation of the efficacy and safety of 150 and 300 mg/d sustainedrelease bupropion tablets versus placebo in depressed outpatients. Author(s): Reimherr FW, Cunningham LA, Batey SR, Johnston JA, Ascher JA. Source: Clinical Therapeutics. 1998 May-June; 20(3): 505-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9663366&dopt=Abstract
Studies
63
•
A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients. Author(s): Margolin A, Kosten TR, Avants SK, Wilkins J, Ling W, Beckson M, Arndt IO, Cornish J, Ascher JA, Li SH, et al. Source: Drug and Alcohol Dependence. 1995 December; 40(2): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8745134&dopt=Abstract
•
A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation. Author(s): Tonnesen P, Tonstad S, Hjalmarson A, Lebargy F, Van Spiegel PI, Hider A, Sweet R, Townsend J. Source: Journal of Internal Medicine. 2003 August; 254(2): 184-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859700&dopt=Abstract
•
A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. Author(s): Evins AE, Mays VK, Rigotti NA, Tisdale T, Cather C, Goff DC. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 November; 3(4): 397-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694208&dopt=Abstract
•
A placebo controlled trial of bupropion for smoking cessation in schizophrenia. Author(s): George TP, Vessicchio JC, Termine A, Bregartner TA, Feingold A, Rounsaville BJ, Kosten TR. Source: Biological Psychiatry. 2002 July 1; 52(1): 53-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079730&dopt=Abstract
•
A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Author(s): Croft H, Settle E Jr, Houser T, Batey SR, Donahue RM, Ascher JA. Source: Clinical Therapeutics. 1999 April; 21(4): 643-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10363731&dopt=Abstract
•
A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine. Author(s): Coleman CC, King BR, Bolden-Watson C, Book MJ, Segraves RT, Richard N, Ascher J, Batey S, Jamerson B, Metz A. Source: Clinical Therapeutics. 2001 July; 23(7): 1040-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519769&dopt=Abstract
64
Bupropion
•
A possible bupropion and imipramine interaction. Author(s): Shad MU, Preskorn SH. Source: Journal of Clinical Psychopharmacology. 1997 April; 17(2): 118-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950476&dopt=Abstract
•
A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder. Author(s): Hertzberg MA, Moore SD, Feldman ME, Beckham JC. Source: Journal of Clinical Psychopharmacology. 2001 February; 21(1): 94-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199956&dopt=Abstract
•
A prospective safety surveillance study for bupropion sustained-release in the treatment of depression. Author(s): Dunner DL, Zisook S, Billow AA, Batey SR, Johnston JA, Ascher JA. Source: The Journal of Clinical Psychiatry. 1998 July; 59(7): 366-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9714265&dopt=Abstract
•
A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants. Author(s): DeBattista C, Solvason HB, Poirier J, Kendrick E, Schatzberg AF. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544372&dopt=Abstract
•
A prospective trial of sustained-release bupropion for depression in HIV-seropositive and AIDS patients. Author(s): Currier MB, Molina G, Kato M. Source: Psychosomatics. 2003 March-April; 44(2): 120-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618534&dopt=Abstract
•
A retrospective survey of the use of bupropion slow release by members of the Canadian Armed Forces. Author(s): Vaillancourt R, Wagenaar H, Fisher C, Conway RD, Plemel J. Source: Can J Clin Pharmacol. 2002 Winter; 9(4): 205-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584579&dopt=Abstract
•
A seizure following bupropion overdose. Author(s): Gittelman DK, Kirby MG. Source: The Journal of Clinical Psychiatry. 1993 April; 54(4): 162. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8486598&dopt=Abstract
Studies
65
•
Absence of orthostatic hypotension in depressed patients treated with bupropion. Author(s): Chouinard G, Annable L, Langlois R. Source: Prog Neuropsychopharmacol. 1981; 5(5-6): 483-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6803273&dopt=Abstract
•
Acute cholestatic hepatitis induced by bupropion prescribed as pharmacological support to stop smoking. A case report. Author(s): Alvaro D, Onetti-Muda A, Moscatelli R, Atili AF. Source: Dig Liver Dis. 2001 November; 33(8): 703-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785718&dopt=Abstract
•
Acute delirium and parkinsonism in a bupropion-treated liver transplant recipient. Author(s): Strouse TB, Salehmoghaddam S, Spar JE. Source: The Journal of Clinical Psychiatry. 1993 December; 54(12): 489-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8276742&dopt=Abstract
•
Acute doses of d-amphetamine and bupropion increase cigarette smoking. Author(s): Cousins MS, Stamat HM, de Wit H. Source: Psychopharmacology. 2001 September; 157(3): 243-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605079&dopt=Abstract
•
Acute hepatitis induced by bupropion. Author(s): Hu KQ, Tiyyagura L, Kanel G, Redeker AG. Source: Digestive Diseases and Sciences. 2000 September; 45(9): 1872-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11052334&dopt=Abstract
•
Acute liver failure with concurrent bupropion and carbimazole therapy. Author(s): Khoo AL, Tham LS, Lee KH, Lim GK. Source: The Annals of Pharmacotherapy. 2003 February; 37(2): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549952&dopt=Abstract
•
Acute myocardial infarction following bupropion (Zyban). Author(s): Patterson RN, Herity NA. Source: Qjm : Monthly Journal of the Association of Physicians. 2002 January; 95(1): 589. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834777&dopt=Abstract
66
Bupropion
•
Acute myocardial ischemia associated with ingestion of bupropion and pseudoephedrine in a 21-year-old man. Author(s): Pederson KJ, Kuntz DH, Garbe GJ. Source: The Canadian Journal of Cardiology. 2001 May; 17(5): 599-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11381283&dopt=Abstract
•
Acute psychosis after administration of bupropion hydrochloride (Zyban). Author(s): Neumann M, Livak V, Paul HW, Laux G. Source: Pharmacopsychiatry. 2002 November; 35(6): 247-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518275&dopt=Abstract
•
ADHD through the life span: the role of bupropion in treatment. Author(s): Cantwell DP. Source: The Journal of Clinical Psychiatry. 1998; 59 Suppl 4: 92-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554326&dopt=Abstract
•
Alcohol and bupropion pharmacokinetics in healthy male volunteers. Author(s): Posner J, Bye A, Jeal S, Peck AW, Whiteman P. Source: European Journal of Clinical Pharmacology. 1984; 26(5): 627-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6432553&dopt=Abstract
•
Amphetamine positive toxicology screen secondary to bupropion. Author(s): Weintraub D, Linder MW. Source: Depression and Anxiety. 2000; 12(1): 53-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10999247&dopt=Abstract
•
Amplitude/intensity functions of auditory event-related potentials predict responsiveness to bupropion in major depressive disorder. Author(s): Paige SR, Hendricks SE, Fitzpatrick DF, Balogh S, Burke WJ. Source: Psychopharmacology Bulletin. 1995; 31(2): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7491375&dopt=Abstract
•
An open pilot study of bupropion and psychotherapy for the treatment of cocaine abuse in methadone-maintained patients. Author(s): Margolin A, Kosten T, Petrakis I, Avants SK, Kosten T. Source: Nida Res Monogr. 1991; 105: 367-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1908556&dopt=Abstract
Studies
67
•
An open trial of bupropion for ADHD in adolescents with substance use disorders and conduct disorder. Author(s): Riggs PD, Leon SL, Mikulich SK, Pottle LC. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1998 December; 37(12): 1271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9847499&dopt=Abstract
•
An open trial of bupropion for the treatment of adults with attentiondeficit/hyperactivity disorder and bipolar disorder. Author(s): Wilens TE, Prince JB, Spencer T, Van Patten SL, Doyle R, Girard K, Hammerness P, Goldman S, Brown S, Biederman J. Source: Biological Psychiatry. 2003 July 1; 54(1): 9-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842303&dopt=Abstract
•
Antidepressant profiles of bupropion and three metabolites: clinical and pre-clinical studies. Author(s): Golden RN. Source: Pharmacopsychiatry. 1991 March; 24(2): 68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1953872&dopt=Abstract
•
Antidepressant response and plasma concentrations of bupropion. Author(s): Preskorn SH. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406443&dopt=Abstract
•
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
•
Ballism associated with bupropion use. Author(s): de Graaf L, Admiraal P, van Puijenbroek EP. Source: The Annals of Pharmacotherapy. 2003 February; 37(2): 302-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549967&dopt=Abstract
•
Bitemporal epileptiform discharges induced by bupropion: a case report. Author(s): Shah GD, Hirsch LJ. Source: Clinical Neuropharmacology. 2001 September-October; 24(5): 304-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586117&dopt=Abstract
68
Bupropion
•
Blood levels and acute response to bupropion. Author(s): Goodnick PJ. Source: The American Journal of Psychiatry. 1992 March; 149(3): 399-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1536282&dopt=Abstract
•
Bupropion (Zyban) for smoking cessation. Author(s): MacConnachie AM. Source: Intensive & Critical Care Nursing : the Official Journal of the British Association of Critical Care Nurses. 2000 August; 16(4): 266-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10922191&dopt=Abstract
•
Bupropion (Zyban) toxicity. Author(s): Tracey JA, Cassidy N, Casey PB, Ali I. Source: Ir Med J. 2002 January; 95(1): 23-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928786&dopt=Abstract
•
Bupropion (Zyban, sustained-release tablets): reported adverse reactions. Author(s): Hebert S. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1999 April 6; 160(7): 1050-1, 1054-5. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10207350&dopt=Abstract
•
Bupropion (Zyban, sustained-release tablets): update. Author(s): Dunlop H. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 January 11; 162(1): 106-7, 110-1. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216185&dopt=Abstract
•
Bupropion (Zyban, Wellbutrin SR): reports of deaths, seizures, serum sickness. Author(s): Wooltorton E. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 January 8; 166(1): 68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800252&dopt=Abstract
•
Bupropion and alcohol fatal intoxication: case report. Author(s): Ramcharitar V, Levine BS, Goldberger BA, Caplan YH. Source: Forensic Science International. 1992 October; 56(2): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1452106&dopt=Abstract
Studies
69
•
Bupropion and amitriptyline in the treatment of depressed patients. Author(s): Chouinard G. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 121-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406440&dopt=Abstract
•
Bupropion and anticonvulsant drug interactions. Author(s): Popli AP, Tanquary J, Lamparella V, Masand PS. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1995 June; 7(2): 99-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8556101&dopt=Abstract
•
Bupropion and compulsive behavior. Author(s): Jacobsen LK, Chappell P, Woolston JL. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1994 January; 33(1): 143-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8138514&dopt=Abstract
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Bupropion and delirium. Author(s): Liberzon I, Dequardo JR, Silk KR. Source: The American Journal of Psychiatry. 1990 December; 147(12): 1689-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2123081&dopt=Abstract
•
Bupropion and drug-induced parkinsonism. Author(s): Jerome L. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 August; 46(6): 560-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11526815&dopt=Abstract
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Bupropion and generalized acute urticaria: eight cases. Author(s): Fays S, Trechot P, Schmutz JL, Cuny JF, Truchetet F, Barbaud A. Source: The British Journal of Dermatology. 2003 January; 148(1): 177-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534623&dopt=Abstract
•
Bupropion and guanfacine. Author(s): Tilton P. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1998 July; 37(7): 682-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9666620&dopt=Abstract
70
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Bupropion and nightmares. Author(s): Balon R. Source: The American Journal of Psychiatry. 1996 April; 153(4): 579-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8599416&dopt=Abstract
•
Bupropion and secondary mania. Is there a relationship? Author(s): Masand P, Stern TA. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1993 December; 5(4): 271-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8312984&dopt=Abstract
•
Bupropion and serum sickness-like reaction. Author(s): Davis JS, Boyle MJ, Hannaford R, Watson A. Source: The Medical Journal of Australia. 2001 May 7; 174(9): 479-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11386597&dopt=Abstract
•
Bupropion and sexual function: a placebo-controlled prospective study on diabetic men with erectile dysfunction. Author(s): Rowland DL, Myers L, Culver A, Davidson JM. Source: Journal of Clinical Psychopharmacology. 1997 October; 17(5): 350-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9315985&dopt=Abstract
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Bupropion and smoking cessation. Author(s): Evins AE, Tisdale T. Source: The American Journal of Psychiatry. 1999 May; 156(5): 798-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10327924&dopt=Abstract
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Bupropion as a promising approach to rapid cycling bipolar II patients. Author(s): Haykal RF, Akiskal HS. Source: The Journal of Clinical Psychiatry. 1990 November; 51(11): 450-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2121720&dopt=Abstract
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Bupropion as add-on strategy in difficult-to-treat bipolar depressive patients. Author(s): Erfurth A, Michael N, Stadtland C, Arolt V. Source: Neuropsychobiology. 2002; 45 Suppl 1: 33-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893875&dopt=Abstract
Studies
71
•
Bupropion as an antidote for serotonin reuptake inhibitor-induced sexual dysfunction. Author(s): Ashton AK, Rosen RC. Source: The Journal of Clinical Psychiatry. 1998 March; 59(3): 112-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9541153&dopt=Abstract
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Bupropion clarification. Author(s): Kent RS. Source: The Journal of Clinical Psychiatry. 1999 March; 60(3): 196. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10192599&dopt=Abstract
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Bupropion coadministration with electroconvulsive therapy: two case reports. Author(s): Kellner CH, Pritchett JT, Jackson CW. Source: Journal of Clinical Psychopharmacology. 1994 June; 14(3): 215-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8027425&dopt=Abstract
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Bupropion does not antagonize cardiovascular actions of clonidine in normal subjects and spontaneously hypertensive rats. Author(s): Cubeddu LX, Cloutier G, Gross K, Grippo R, Tanner L, Lerea L, Shakarjian M, Knowlton G, Stat M, Harden TK, et al. Source: Clinical Pharmacology and Therapeutics. 1984 May; 35(5): 576-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6424997&dopt=Abstract
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Bupropion dose, seizures, women, and age. Author(s): Goldberg JP. Source: The Journal of Clinical Psychiatry. 1990 September; 51(9): 388-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2120202&dopt=Abstract
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Bupropion dosing recommendations. Author(s): Ionescu-Pioggia M, Johnston JA. Source: The Journal of Clinical Psychiatry. 1989 October; 50(10): 392. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2507533&dopt=Abstract
•
Bupropion dosing recommendations. Author(s): Davidson JR. Source: The Journal of Clinical Psychiatry. 1990 February; 51(2): 83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2105308&dopt=Abstract
72
Bupropion
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Bupropion effects in attention deficit and conduct disorders. Author(s): Simeon JG, Ferguson HB, Van Wyck Fleet J. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1986 August; 31(6): 581-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3093046&dopt=Abstract
•
Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette's syndrome. Author(s): Spencer T, Biederman J, Steingard R, Wilens T. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1993 January; 32(1): 211-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8428875&dopt=Abstract
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Bupropion exposures: clinical manifestations and medical outcome. Author(s): Belson MG, Kelley TR. Source: The Journal of Emergency Medicine. 2002 October; 23(3): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426011&dopt=Abstract
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Bupropion fails to affect plasma prolactin and growth hormone in normal subjects. Author(s): Whiteman PD, Peck AW, Fowle AS, Smith P. Source: British Journal of Clinical Pharmacology. 1982 May; 13(5): 743-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6805494&dopt=Abstract
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Bupropion for adults with attention deficit hyperactivity disorder. Author(s): Newcorn JH. Source: Current Psychiatry Reports. 2002 April; 4(2): 86-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174849&dopt=Abstract
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Bupropion for amphetamine withdrawal syndrome. Author(s): Chan-Ob T, Kuntawongse N, Boonyanaruthee V. Source: J Med Assoc Thai. 2001 December; 84(12): 1763-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999825&dopt=Abstract
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Bupropion for pharmacologic relapse prevention to smoking: predictors of outcome. Author(s): Hurt RD, Wolter TD, Rigotti N, Hays JT, Niaura R, Durcan MJ, Gonzales D, Sachs DP, Johnston JA, Offord KP. Source: Addictive Behaviors. 2002 July-August; 27(4): 493-507. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188588&dopt=Abstract
Studies
73
•
Bupropion for smokers. Bupropion may not be as good as editorial implies. Author(s): Harrison C. Source: Bmj (Clinical Research Ed.). 2001 February 17; 322(7283): 431; Author Reply 4323. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179179&dopt=Abstract
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Bupropion for smokers. Drug is almost identical in structure to diethylpropion, a controlled drug. Author(s): Kinnell HG. Source: Bmj (Clinical Research Ed.). 2001 February 17; 322(7283): 431-2; Author Reply 432-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179153&dopt=Abstract
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Bupropion for smokers. New products for smoking cessation maintain profile of smoking cessation services. Author(s): Richardson W. Source: Bmj (Clinical Research Ed.). 2001 February 17; 322(7283): 432; Discussuion 432-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179164&dopt=Abstract
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Bupropion for smokers. Where are practices supposed to find money for bupropion? Author(s): Vautrey R. Source: Bmj (Clinical Research Ed.). 2001 February 17; 322(7283): 432-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179167&dopt=Abstract
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Bupropion for smoking cessation : predictors of successful outcome. Author(s): Dale LC, Glover ED, Sachs DP, Schroeder DR, Offord KP, Croghan IT, Hurt RD. Source: Chest. 2001 May; 119(5): 1357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11348939&dopt=Abstract
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Bupropion for smoking cessation. Author(s): Jackson EA. Source: The Journal of Family Practice. 1998 February; 46(2): 111-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9487309&dopt=Abstract
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Bupropion for smoking cessation: from the rationale to the quantitative aspects of the results. Author(s): Van Meerhaeghe A. Source: Acta Cardiol. 2001 October; 56(5): 319-21. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712828&dopt=Abstract
74
Bupropion
•
Bupropion for SSRI-induced fatigue. Author(s): Green TR. Source: The Journal of Clinical Psychiatry. 1997 April; 58(4): 174. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9164429&dopt=Abstract
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Bupropion for the treatment of fatigue associated with multiple sclerosis. Author(s): Duffy JD, Campbell J. Source: Psychosomatics. 1994 March-April; 35(2): 170-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8171179&dopt=Abstract
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Bupropion for the treatment of nicotine dependence in spit tobacco users: a pilot study. Author(s): Dale LC, Ebbert JO, Schroeder DR, Croghan IT, Rasmussen DF, Trautman JA, Cox LS, Hurt RD. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002 August; 4(3): 267-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215235&dopt=Abstract
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Bupropion for the treatment of tobacco dependence: guidelines for balancing risks and benefits. Author(s): Hays JT, Ebbert JO. Source: Cns Drugs. 2003; 17(2): 71-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521356&dopt=Abstract
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Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women. Author(s): Gadde KM, Parker CB, Maner LG, Wagner HR 2nd, Logue EJ, Drezner MK, Krishnan KR. Source: Obesity Research. 2001 September; 9(9): 544-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11557835&dopt=Abstract
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Bupropion hydrochloride in attention deficit disorder with hyperactivity. Author(s): Conners CK, Casat CD, Gualtieri CT, Weller E, Reader M, Reiss A, Weller RA, Khayrallah M, Ascher J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1996 October; 35(10): 1314-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8885585&dopt=Abstract
Studies
75
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Bupropion hydrochloride induced serum sickness-like reaction. Author(s): Tripathi A, Greenberger PA. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 1999 August; 83(2): 165-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10480592&dopt=Abstract
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Bupropion hydrochloride. Author(s): Dufresne RL, Weber SS, Becker RE. Source: Drug Intell Clin Pharm. 1984 December; 18(12): 957-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6439541&dopt=Abstract
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Bupropion in children with attention deficit disorder. Author(s): Casat CD, Pleasants DZ, Schroeder DH, Parler DW. Source: Psychopharmacology Bulletin. 1989; 25(2): 198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2513592&dopt=Abstract
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Bupropion in chronic fatigue syndrome. Author(s): Goodnick PJ. Source: The American Journal of Psychiatry. 1990 August; 147(8): 1091. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2115748&dopt=Abstract
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Bupropion in chronic low back pain. Author(s): Davidson JR, France RD. Source: The Journal of Clinical Psychiatry. 1994 August; 55(8): 362. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8071306&dopt=Abstract
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Bupropion in depression. I. Biochemical effects and clinical response. Author(s): Golden RN, Rudorfer MV, Sherer MA, Linnoila M, Potter WZ. Source: Archives of General Psychiatry. 1988 February; 45(2): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3122698&dopt=Abstract
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Bupropion in depression. II. The role of metabolites in clinical outcome. Author(s): Golden RN, De Vane CL, Laizure SC, Rudorfer MV, Sherer MA, Potter WZ. Source: Archives of General Psychiatry. 1988 February; 45(2): 145-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3122699&dopt=Abstract
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Bupropion in depression: a tri-center placebo-controlled study. Author(s): Pitts WM, Fann WE, Halaris AE, Dressler DM, Sajadi C, Snyder S, Ilaria RL. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406473&dopt=Abstract
76
Bupropion
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Bupropion in Parkinson's disease. Author(s): Goetz CG, Tanner CM, Klawans HL. Source: Neurology. 1984 August; 34(8): 1092-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6431314&dopt=Abstract
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Bupropion in the long-term treatment of cyclic mood disorders: mood stabilizing effects. Author(s): Wright G, Galloway L, Kim J, Dalton M, Miller L, Stern W. Source: The Journal of Clinical Psychiatry. 1985 January; 46(1): 22-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2856918&dopt=Abstract
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Bupropion in the treatment of bipolar disorders: the same old story? Author(s): Fogelson DL, Bystritsky A, Pasnau R. Source: The Journal of Clinical Psychiatry. 1992 December; 53(12): 443-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1487473&dopt=Abstract
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Bupropion in the treatment of psychotic depression: two case reports. Author(s): Manberg PJ, Carter RG. Source: The Journal of Clinical Psychiatry. 1984 May; 45(5): 230-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6427198&dopt=Abstract
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Bupropion in tricyclic antidepressant nonresponders with unipolar major depressive disorder. Author(s): Ferguson J, Cunningham L, Merideth C, Apter J, Feighner J, Ionescu-Pioggia M, Samara B, Johnston JA, Ascher J. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1994 September; 6(3): 153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7881495&dopt=Abstract
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Bupropion manic induction during euthymia, but not during depression. Author(s): El-Mallakh RS. Source: Bipolar Disorders. 2001 June; 3(3): 159-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465677&dopt=Abstract
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Bupropion metabolites produce false-positive urine amphetamine results. Author(s): Nixon AL, Long WH, Puopolo PR, Flood JG. Source: Clinical Chemistry. 1995 June; 41(6 Pt 1): 955-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7768026&dopt=Abstract
Studies
77
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Bupropion mimics a transient ischemic attack. Author(s): Humma LM, Swims MP. Source: The Annals of Pharmacotherapy. 1999 March; 33(3): 305-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200854&dopt=Abstract
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Bupropion occupancy of the dopamine transporter is low during clinical treatment. Author(s): Meyer JH, Goulding VS, Wilson AA, Hussey D, Christensen BK, Houle S. Source: Psychopharmacology. 2002 August; 163(1): 102-5. Epub 2002 July 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185406&dopt=Abstract
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Bupropion or patch for smoking cessation? Author(s): Kane KY, Ellis MR. Source: The Journal of Family Practice. 1999 June; 48(6): 419. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10386482&dopt=Abstract
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Bupropion overdose and seizure. Author(s): Storrow AB. Source: The American Journal of Emergency Medicine. 1994 March; 12(2): 183-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8161393&dopt=Abstract
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Bupropion overdose in an adolescent. Author(s): Ayers S, Tobias JD. Source: Pediatric Emergency Care. 2001 April; 17(2): 104-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334088&dopt=Abstract
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Bupropion overdose: a 3-year multi-center retrospective analysis. Author(s): Spiller HA, Ramoska EA, Krenzelok EP, Sheen SR, Borys DJ, Villalobos D, Muir S, Jones-Easom L. Source: The American Journal of Emergency Medicine. 1994 January; 12(1): 43-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8285970&dopt=Abstract
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Bupropion overdose: a potential problem with the new 'miracle' anti-smoking drug. Author(s): Bhattacharjee C, Smith M, Todd F, Gillespie M. Source: Int J Clin Pract. 2001 April; 55(3): 221-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351778&dopt=Abstract
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Bupropion overdose: QTc prolongation and its clinical significance. Author(s): Isbister GK, Balit CR. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 999-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841807&dopt=Abstract
78
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Bupropion plasma levels and CYP2D6 phenotype. Author(s): Pollock BG, Sweet RA, Kirshner M, Reynolds CF 3rd. Source: Therapeutic Drug Monitoring. 1996 October; 18(5): 581-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8885123&dopt=Abstract
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Bupropion poisoning: a case series. Author(s): Balit CR, Lynch CN, Isbister GK. Source: The Medical Journal of Australia. 2003 January 20; 178(2): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526723&dopt=Abstract
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Bupropion reduces cocaine abuse in methadone-maintained patients. Author(s): Margolin A, Kosten T, Petrakis I, Avants SK, Kosten T. Source: Archives of General Psychiatry. 1991 January; 48(1): 87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1898631&dopt=Abstract
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Bupropion seizure proportion among new-onset generalized seizures and drug related seizures presenting to an emergency department. Author(s): Pesola GR, Avasarala J. Source: The Journal of Emergency Medicine. 2002 April; 22(3): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932084&dopt=Abstract
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Bupropion slow-release response in depression: diagnosis and biochemistry. Author(s): Goodnick PJ, Dominguez RA, DeVane CL, Bowden CL. Source: Biological Psychiatry. 1998 October 1; 44(7): 629-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9787888&dopt=Abstract
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Bupropion SR and smoking cessation in actual practice: methods for recruitment, screening, and exclusion for a field trial in a managed-care setting. Author(s): Jack LM, Swan GE, Thompson E, Curry SJ, McAfee T, Dacey S, Bergman K. Source: Preventive Medicine. 2003 May; 36(5): 585-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689804&dopt=Abstract
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Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: a randomized placebo-controlled study. Author(s): Gonzales DH, Nides MA, Ferry LH, Kustra RP, Jamerson BD, Segall N, Herrero LA, Krishen A, Sweeney A, Buaron K, Metz A. Source: Clinical Pharmacology and Therapeutics. 2001 June; 69(6): 438-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406741&dopt=Abstract
Studies
79
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Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial. Author(s): Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O'Neil PM. Source: Obesity Research. 2002 July; 10(7): 633-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105285&dopt=Abstract
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Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study. Author(s): Tonstad S, Farsang C, Klaene G, Lewis K, Manolis A, Perruchoud AP, Silagy C, van Spiegel PI, Astbury C, Hider A, Sweet R. Source: European Heart Journal. 2003 May; 24(10): 946-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714026&dopt=Abstract
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Bupropion SR for smoking cessation. Author(s): West R. Source: Expert Opinion on Pharmacotherapy. 2003 April; 4(4): 533-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667116&dopt=Abstract
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Bupropion SR in the naturalistic treatment of elderly patients with major depression. Author(s): Steffens DC, Doraiswamy PM, McQuoid DR. Source: International Journal of Geriatric Psychiatry. 2001 September; 16(9): 862-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571765&dopt=Abstract
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Bupropion SR reduces periodic limb movements associated with arousals from sleep in depressed patients with periodic limb movement disorder. Author(s): Nofzinger EA, Fasiczka A, Berman S, Thase ME. Source: The Journal of Clinical Psychiatry. 2000 November; 61(11): 858-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105739&dopt=Abstract
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Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults. Author(s): Kuperman S, Perry PJ, Gaffney GR, Lund BC, Bever-Stille KA, Arndt S, Holman TL, Moser DJ, Paulsen JS. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 2001 September; 13(3): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791949&dopt=Abstract
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Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms. Author(s): Jain AK, Kaplan RA, Gadde KM, Wadden TA, Allison DB, Brewer ER, Leadbetter RA, Richard N, Haight B, Jamerson BD, Buaron KS, Metz A. Source: Obesity Research. 2002 October; 10(10): 1049-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376586&dopt=Abstract
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Bupropion SR worsens mood during marijuana withdrawal in humans. Author(s): Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW. Source: Psychopharmacology. 2001 May; 155(2): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401006&dopt=Abstract
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Bupropion sustained release (SR) for the treatment of hypoactive sexual desire disorder (HSDD) in nondepressed women. Author(s): Segraves RT, Croft H, Kavoussi R, Ascher JA, Batey SR, Foster VJ, BoldenWatson C, Metz A. Source: Journal of Sex & Marital Therapy. 2001 May-June; 27(3): 303-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11354935&dopt=Abstract
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Bupropion sustained release and smoking cessation. Author(s): Goldstein MG. Source: The Journal of Clinical Psychiatry. 1998; 59 Suppl 4: 66-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554323&dopt=Abstract
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Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on treatment with selective serotonin reuptake inhibitor antidepressants. Author(s): Chengappa KN, Kambhampati RK, Perkins K, Nigam R, Anderson T, Brar JS, Vemulapalli HK, Atzert R, Key P, Kang JS, Levine J. Source: The Journal of Clinical Psychiatry. 2001 July; 62(7): 503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488359&dopt=Abstract
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Bupropion sustained release for bereavement: results of an open trial. Author(s): Zisook S, Shuchter SR, Pedrelli P, Sable J, Deaciuc SC. Source: The Journal of Clinical Psychiatry. 2001 April; 62(4): 227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11379835&dopt=Abstract
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Bupropion sustained release for treatment of tobacco dependence. Author(s): Hays JT, Ebbert JO. Source: Mayo Clinic Proceedings. 2003 August; 78(8): 1020-4; Quiz 1024. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911050&dopt=Abstract
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81
•
Bupropion sustained release in adolescents with comorbid attentiondeficit/hyperactivity disorder and depression. Author(s): Daviss WB, Bentivoglio P, Racusin R, Brown KM, Bostic JQ, Wiley L. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 March; 40(3): 307-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11288772&dopt=Abstract
•
Bupropion sustained release versus paroxetine for the treatment of depression in the elderly. Author(s): Weihs KL, Settle EC Jr, Batey SR, Houser TL, Donahue RM, Ascher JA. Source: The Journal of Clinical Psychiatry. 2000 March; 61(3): 196-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10817105&dopt=Abstract
•
Bupropion sustained release. A therapeutic review of Zyban. Author(s): Zwar N, Richmond R. Source: Aust Fam Physician. 2002 May; 31(5): 443-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043548&dopt=Abstract
•
Bupropion sustained release: a therapeutic overview. Author(s): Davidson JR, Connor KM. Source: The Journal of Clinical Psychiatry. 1998; 59 Suppl 4: 25-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554318&dopt=Abstract
•
Bupropion sustained release: side effect profile. Author(s): Settle EC Jr. Source: The Journal of Clinical Psychiatry. 1998; 59 Suppl 4: 32-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554319&dopt=Abstract
•
Bupropion sustained-release for the treatment of dysthymic disorder: an open-label study. Author(s): Hellerstein DJ, Batchelder S, Kreditor D, Fedak M. Source: Journal of Clinical Psychopharmacology. 2001 June; 21(3): 325-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11386496&dopt=Abstract
•
Bupropion treatment for cocaine abuse and adult attention-deficit/hyperactivity disorder. Author(s): Levin FR, Evans SM, McDowell DM, Brooks DJ, Nunes E. Source: J Addict Dis. 2002; 21(2): 1-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916368&dopt=Abstract
82
Bupropion
•
Bupropion treatment in veterans with posttraumatic stress disorder: an open study. Author(s): Canive JM, Clark RD, Calais LA, Qualls C, Tuason VB. Source: Journal of Clinical Psychopharmacology. 1998 October; 18(5): 379-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9790155&dopt=Abstract
•
Bupropion treatment of attention-deficit hyperactivity disorder in adults. Author(s): Wender PH, Reimherr FW. Source: The American Journal of Psychiatry. 1990 August; 147(8): 1018-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2115746&dopt=Abstract
•
Bupropion treatment of depression to assist smoking cessation. Author(s): Lief HI. Source: The American Journal of Psychiatry. 1996 March; 153(3): 442. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8610840&dopt=Abstract
•
Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome. Author(s): Goodnick PJ, Sandoval R, Brickman A, Klimas NG. Source: Biological Psychiatry. 1992 November 1; 32(9): 834-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1450297&dopt=Abstract
•
Bupropion treatment of refractory depression. Author(s): Katz SE. Source: Journal of Clinical Psychopharmacology. 1987 February; 7(1): 51-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3102564&dopt=Abstract
•
Bupropion treatment of serotonin reuptake antidepressant-associated sexual dysfunction. Author(s): Labbate LA, Grimes JB, Hines A, Pollack MH. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1997 December; 9(4): 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9511948&dopt=Abstract
•
Bupropion treatment-related sexual side effects: a case report. Author(s): Ramasubbu R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2000 March; 45(2): 200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10742886&dopt=Abstract
Studies
83
•
Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. Author(s): Barrickman LL, Perry PJ, Allen AJ, Kuperman S, Arndt SV, Herrmann KJ, Schumacher E. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1995 May; 34(5): 649-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7775360&dopt=Abstract
•
Bupropion versus selective serotonin-reuptake inhibitors for treatment of depression. Author(s): Nieuwstraten CE, Dolovich LR. Source: The Annals of Pharmacotherapy. 2001 December; 35(12): 1608-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793630&dopt=Abstract
•
Bupropion, ECT, and dopaminergic overdrive. Author(s): Rudorfer MV, Manji HK, Potter WZ. Source: The American Journal of Psychiatry. 1991 August; 148(8): 1101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1906685&dopt=Abstract
•
Bupropion, is it here to stay? Author(s): Carson SW. Source: Dicp. 1989 September; 23(9): 704-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2508333&dopt=Abstract
•
Bupropion, periodic limb movement disorder, and ADHD. Author(s): Malek-Ahmadi P. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1999 June; 38(6): 637-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10361776&dopt=Abstract
•
Bupropion. Author(s): Harsch HH. Source: American Family Physician. 1991 June; 43(6): 1947-50, 1952. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1904187&dopt=Abstract
•
Bupropion/nortriptyline combination for refractory depression. Author(s): Apter JT, Kushner SF, Woolfolk RL. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1994 December; 6(4): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7647835&dopt=Abstract
84
Bupropion
•
Bupropion: a new clinical profile in the psychobiology of depression. Author(s): Shopsin B. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 140-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406445&dopt=Abstract
•
Bupropion: a new treatment for smokers. Nicotine replacement treatment should also be available on the NHS. Author(s): Britton J, Jarvis MJ. Source: Bmj (Clinical Research Ed.). 2000 July 8; 321(7253): 65-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10884238&dopt=Abstract
•
Bupropion: a review of its mechanism of antidepressant activity. Author(s): Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter WZ, Richelson E, et al. Source: The Journal of Clinical Psychiatry. 1995 September; 56(9): 395-401. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7665537&dopt=Abstract
•
Bupropion: a review of its use in the management of smoking cessation. Author(s): Holm KJ, Spencer CM. Source: Drugs. 2000 April; 59(4): 1007-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10804045&dopt=Abstract
•
Bupropion: clinical assay for amphetamine-like abuse potential. Author(s): Griffith JD, Carranza J, Griffith C, Miller LL. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 206-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406459&dopt=Abstract
•
Bupropion: new therapy for depression. Author(s): Feinberg M. Source: American Family Physician. 1990 June; 41(6): 1787-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2112333&dopt=Abstract
•
Bupropion: overview and prescribing guidelines in depression. Author(s): James WA, Lippmann S. Source: Southern Medical Journal. 1991 February; 84(2): 222-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1899294&dopt=Abstract
•
Bupropion: pharmacological and clinical profile in smoking cessation. Author(s): Haustein KO. Source: Int J Clin Pharmacol Ther. 2003 February; 41(2): 56-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607628&dopt=Abstract
Studies
85
•
Bupropion: study of treatment in depressed patients. Author(s): Ajac IK, Giroux LJ, Hill JA. Source: J Fla Med Assoc. 1983 May; 70(5): 356-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6409980&dopt=Abstract
•
Bupropion-amantadine-associated neurotoxicity. Author(s): Trappler B, Miyashiro AM. Source: The Journal of Clinical Psychiatry. 2000 January; 61(1): 61-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695649&dopt=Abstract
•
Bupropion--an antidepressant without sexual pathophysiological action. Author(s): Gardner EA, Johnston JA. Source: Journal of Clinical Psychopharmacology. 1985 February; 5(1): 24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3919069&dopt=Abstract
•
Bupropion-associated mania in a patient with HIV infection. Author(s): Fichtner CG, Braun BG. Source: Journal of Clinical Psychopharmacology. 1992 October; 12(5): 366-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1479060&dopt=Abstract
•
Bupropion-induced acute dystonia. Author(s): Detweiler MB, Harpold GJ. Source: The Annals of Pharmacotherapy. 2002 February; 36(2): 251-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847943&dopt=Abstract
•
Bupropion-induced carbohydrate craving and weight gain. Author(s): Workman EA, Short DD. Source: The American Journal of Psychiatry. 1992 October; 149(10): 1407-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1530081&dopt=Abstract
•
Bupropion-induced erythema multiforme. Author(s): Lineberry TW, Peters GE Jr, Bostwick JM. Source: Mayo Clinic Proceedings. 2001 June; 76(6): 664-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393509&dopt=Abstract
•
Bupropion-induced hypersensitivity reactions. Author(s): Benson E. Source: The Medical Journal of Australia. 2001 June 18; 174(12): 650-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480688&dopt=Abstract
86
Bupropion
•
Bupropion-induced isolated impairment of sensory trigeminal nerve function. Author(s): Amann B, Hummel B, Rall-Autenrieth H, Walden J, Grunze H. Source: International Clinical Psychopharmacology. 2000 March; 15(2): 115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10759343&dopt=Abstract
•
Bupropion-induced psychosis. Author(s): Howard WT, Warnock JK. Source: The American Journal of Psychiatry. 1999 December; 156(12): 2017-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10588428&dopt=Abstract
•
Bupropion-induced serum sickness-like reaction. Author(s): McCollom RA, Elbe DH, Ritchie AH. Source: The Annals of Pharmacotherapy. 2000 April; 34(4): 471-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772432&dopt=Abstract
•
Bupropion-methylphenidate combination and grand mal seizures. Author(s): Ickowicz A. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 October; 47(8): 790-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420664&dopt=Abstract
•
Bupropion-SR in treatment of social phobia. Author(s): Emmanuel NP, Brawman-Mintzer O, Morton WA, Book SW, Johnson MR, Lorberbaum JP, Ballenger JC, Lydiard RB. Source: Depression and Anxiety. 2000; 12(2): 111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11091936&dopt=Abstract
•
Bupropion-SR-induced increased libido and spontaneous orgasm. Author(s): Labbate LA. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1998 August; 43(6): 644-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9729695&dopt=Abstract
•
Bupropion-sustained release as a treatment for SSRI-induced sexual side effects. Author(s): Gitlin MJ, Suri R, Altshuler L, Zuckerbrow-Miller J, Fairbanks L. Source: Journal of Sex & Marital Therapy. 2002 March-April; 28(2): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894796&dopt=Abstract
Studies
87
•
Bupropion-tranylcypromine combination for treatment-refractory depression. Author(s): Pierre JM, Gitlin MJ. Source: The Journal of Clinical Psychiatry. 2000 June; 61(6): 450-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10901349&dopt=Abstract
•
Carbamazepine but not valproate induces bupropion metabolism. Author(s): Ketter TA, Jenkins JB, Schroeder DH, Pazzaglia PJ, Marangell LB, George MS, Callahan AM, Hinton ML, Chao J, Post RM. Source: Journal of Clinical Psychopharmacology. 1995 October; 15(5): 327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8830063&dopt=Abstract
•
Cardiotoxicity associated with bupropion overdose. Author(s): Shrier M, Diaz JE, Tsarouhas N. Source: Annals of Emergency Medicine. 2000 January; 35(1): 100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10613954&dopt=Abstract
•
Cardiotoxicity associated with intentional ziprasidone and bupropion overdose. Author(s): Biswas AK, Zabrocki LA, Mayes KL, Morris-Kukoski CL. Source: Journal of Toxicology. Clinical Toxicology. 2003; 41(2): 101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733844&dopt=Abstract
•
Cardiotoxicity associated with intentional ziprasidone and bupropion overdose. Author(s): Biswas AK, Zabrocki LA, Mayes KL, Morris-Kukoski CL. Source: Journal of Toxicology. Clinical Toxicology. 2003; 41(1): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645973&dopt=Abstract
•
Cardiotoxicity following bupropion overdose. Author(s): Druteika D, Zed PJ. Source: The Annals of Pharmacotherapy. 2002 November; 36(11): 1791-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398578&dopt=Abstract
•
Cardiovascular effects of bupropion in depressed patients with heart disease. Author(s): Roose SP, Dalack GW, Glassman AH, Woodring S, Walsh BT, Giardina EG. Source: The American Journal of Psychiatry. 1991 April; 148(4): 512-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1900980&dopt=Abstract
•
Cardiovascular effects of imipramine and bupropion in depressed patients with congestive heart failure. Author(s): Roose SP, Glassman AH, Giardina EG, Johnson LL, Walsh BT, Bigger JT Jr. Source: Journal of Clinical Psychopharmacology. 1987 August; 7(4): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3114333&dopt=Abstract
88
Bupropion
•
Catatonia associated with bupropion treatment. Author(s): Jackson CW, Head LA, Kellner CH. Source: The Journal of Clinical Psychiatry. 1992 June; 53(6): 210. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1607350&dopt=Abstract
•
Cessation of nail-biting and bupropion. Author(s): Wadden P, Pawliuk G. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1999 September; 44(7): 709-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500877&dopt=Abstract
•
Change from Mg-pemoline to bupropion in a 12-year-old boy with attention-deficit hyperactivity disorder. Author(s): Bloomingdale LM. Source: Journal of Clinical Psychopharmacology. 1990 October; 10(5): 382-3. Erratum In: J Clin Psychopharmacol 1991 April; 11(2): 126. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2124222&dopt=Abstract
•
Change from the CYP2D6 extensive metabolizer to the poor metabolizer phenotype during treatment With bupropion. Author(s): Guzey C, Norstrom A, Spigset O. Source: Therapeutic Drug Monitoring. 2002 June; 24(3): 436-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021638&dopt=Abstract
•
Clinical and neuropsychological effects of the novel antidepressant bupropion. Author(s): Clay TH, Gualtieri CT, Evans RW, Gullion CM. Source: Psychopharmacology Bulletin. 1988; 24(1): 143-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3133717&dopt=Abstract
•
Clinical effectiveness of sustained-release bupropion and behavior therapy for tobacco dependence in a clinical setting. Author(s): Earles J, Folen RA, Ma M, Kellar M, Geralde R, Dydek C. Source: Military Medicine. 2002 November; 167(11): 923-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448619&dopt=Abstract
•
Clinical efficacy of bupropion in the management of smoking cessation. Author(s): Jorenby D. Source: Drugs. 2002; 62 Suppl 2: 25-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109933&dopt=Abstract
Studies
89
•
Clinical pharmacokinetics of bupropion: a review. Author(s): Lai AA, Schroeder DH. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 82-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406470&dopt=Abstract
•
Clinical pharmacology of bupropion and imipramine in elderly depressives. Author(s): Branconnier RJ, Cole JO, Ghazvinian S, Spera KF, Oxenkrug GF, Bass JL. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 130-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406441&dopt=Abstract
•
Clinical profile of the novel antidepressant bupropion. Author(s): Stern WC, Harto-Truax N, Rogers J, Miller L. Source: Adv Biochem Psychopharmacol. 1982; 32: 21-34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6807060&dopt=Abstract
•
Combination treatment with venlafaxine and bupropion. Author(s): Kirsch MA, Louie AK. Source: The American Journal of Psychiatry. 1999 March; 156(3): 494. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080572&dopt=Abstract
•
Combined bupropion-levodopa-trazodone therapy of sleep-related eating and sleep disruption in two adults with chemical dependency. Author(s): Schenck CH, Mahowald MW. Source: Sleep. 2000 August 1; 23(5): 587-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947025&dopt=Abstract
•
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
•
Combining serotonin reuptake inhibitors and bupropion in partial responders to antidepressant monotherapy. Author(s): Bodkin JA, Lasser RA, Wines JD Jr, Gardner DM, Baldessarini RJ. Source: The Journal of Clinical Psychiatry. 1997 April; 58(4): 137-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9164423&dopt=Abstract
90
Bupropion
•
Comparative efficacy and safety of bupropion and placebo in the treatment of depression. Author(s): Zung WW, Brodie HK, Fabre L, McLendon D, Garver D. Source: Psychopharmacology. 1983; 79(4): 343-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6407050&dopt=Abstract
•
Comparative sexual side effects of bupropion, fluoxetine, paroxetine, and sertraline. Author(s): Modell JG, Katholi CR, Modell JD, DePalma RL. Source: Clinical Pharmacology and Therapeutics. 1997 April; 61(4): 476-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9129565&dopt=Abstract
•
Comparison of bupropion alone and with haloperidol in schizo-affective disorder, depressed type. Author(s): Goode DJ, Manning AA. Source: The Journal of Clinical Psychiatry. 1983 July; 44(7): 253-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6408068&dopt=Abstract
•
Comparison of bupropion and trazodone for the treatment of major depression. Author(s): Weisler RH, Johnston JA, Lineberry CG, Samara B, Branconnier RJ, Billow AA. Source: Journal of Clinical Psychopharmacology. 1994 June; 14(3): 170-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8027413&dopt=Abstract
•
Comparison of fluoxetine, bupropion, and placebo in the treatment of premenstrual dysphoric disorder. Author(s): Pearlstein TB, Stone AB, Lund SA, Scheft H, Zlotnick C, Brown WA. Source: Journal of Clinical Psychopharmacology. 1997 August; 17(4): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9241004&dopt=Abstract
•
Comparison of the effects of bupropion and amitriptyline on cardiac conduction in depressed patients. Author(s): Wenger TL, Cohn JB, Bustrack J. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 174-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406452&dopt=Abstract
•
Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. Author(s): Preskorn SH. Source: The Journal of Clinical Psychiatry. 1995; 56 Suppl 6: 12-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7649968&dopt=Abstract
Studies
91
•
Concurrent use of bupropion with CYP2B6 inhibitors, nelfinavir, ritonavir and efavirenz: a case series. Author(s): Park-Wyllie LY, Antoniou T. Source: Aids (London, England). 2003 March 7; 17(4): 638-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598790&dopt=Abstract
•
Conformational analysis and a crystal structure of bupropion, an antidepressant with dopamine reuptake blocking activity. Author(s): Froimowitz M, George C. Source: Journal of Chemical Information and Computer Sciences. 1998 May-June; 38(3): 506-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9611786&dopt=Abstract
•
Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression. Author(s): Weihs KL, Houser TL, Batey SR, Ascher JA, Bolden-Watson C, Donahue RM, Metz A. Source: Biological Psychiatry. 2002 May 1; 51(9): 753-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983189&dopt=Abstract
•
Cost-benefit analysis of sustained-release bupropion, nicotine patch, or both for smoking cessation. Author(s): Nielsen K, Fiore MC. Source: Preventive Medicine. 2000 March; 30(3): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10684744&dopt=Abstract
•
Current prescribing patterns of bupropion in Australia. Author(s): Doran CM, Shakeshaft AP, Gates JA, Fawcett JE, Mattick RP. Source: The Medical Journal of Australia. 2002 August 5; 177(3): 162. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149090&dopt=Abstract
•
CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Author(s): Hesse LM, Venkatakrishnan K, Court MH, von Moltke LL, Duan SX, Shader RI, Greenblatt DJ. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2000 October; 28(10): 1176-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997936&dopt=Abstract
92
Bupropion
•
Delirium associated with bupropion. Author(s): van Putten T, Shaffer I. Source: Journal of Clinical Psychopharmacology. 1990 June; 10(3): 234. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2115897&dopt=Abstract
•
Depressive mania: response of residual depression to bupropion. Author(s): Brown ES, Dilsaver SC, Shoaib AM, Swann AC. Source: Biological Psychiatry. 1994 April 1; 35(7): 493-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8018802&dopt=Abstract
•
Determination of bupropion and its major basic metabolites in plasma by liquid chromatography with dual-wavelength ultraviolet detection. Author(s): Cooper TB, Suckow RF, Glassman A. Source: Journal of Pharmaceutical Sciences. 1984 August; 73(8): 1104-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6436464&dopt=Abstract
•
Determination of plasma bupropion and its relationship to therapeutic effect. Author(s): Fogel P, Mamer OA, Chouinard G, Farrell PG. Source: Biomed Mass Spectrom. 1984 December; 11(12): 629-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6442168&dopt=Abstract
•
Development of depression during placebo-controlled trials of bupropion for smoking cessation: case reports. Author(s): Patten CA, Rummans TA, Croghan IT, Hurt RD, Hays JT. Source: The Journal of Clinical Psychiatry. 1999 July; 60(7): 436-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453796&dopt=Abstract
•
Diethylpropion, bupropion, and psychoses. Author(s): Golden RN. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1988 August; 153: 265-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3151278&dopt=Abstract
•
Differential effect of amitriptyline and bupropion on primary and secondary depression: a pilot study. Author(s): Othmer SC, Othmer E, Preskorn SH, Mac D. Source: The Journal of Clinical Psychiatry. 1988 August; 49(8): 310-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3137218&dopt=Abstract
Studies
93
•
Discriminative-stimulus and participant-rated effects of methylphenidate, bupropion, and triazolam in d-amphetamine-trained humans. Author(s): Rush CR, Kollins SH, Pazzaglia PJ. Source: Experimental and Clinical Psychopharmacology. 1998 February; 6(1): 32-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9526144&dopt=Abstract
•
Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease. Author(s): DeVane CL, Laizure SC, Stewart JT, Kolts BE, Ryerson EG, Miller RL, Lai AA. Source: Journal of Clinical Psychopharmacology. 1990 October; 10(5): 328-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2124217&dopt=Abstract
•
Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients? Author(s): Trivedi MH, Rush AJ, Carmody TJ, Donahue RM, Bolden-Watson C, Houser TL, Metz A. Source: The Journal of Clinical Psychiatry. 2001 October; 62(10): 776-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11816866&dopt=Abstract
•
Does long-term bupropion (Zyban) use prevent smoking relapse after initial success at quitting smoking? Author(s): Barringer TA, Weaver EM. Source: The Journal of Family Practice. 2002 February; 51(2): 172. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978218&dopt=Abstract
•
Does pretreatment anxiety predict response to either bupropion SR or sertraline? Author(s): Rush AJ, Batey SR, Donahue RM, Ascher JA, Carmody TJ, Metz A. Source: Journal of Affective Disorders. 2001 April; 64(1): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292522&dopt=Abstract
•
Double-blind comparison of bupropion and fluoxetine in depressed outpatients. Author(s): Feighner JP, Gardner EA, Johnston JA, Batey SR, Khayrallah MA, Ascher JA, Lineberry CG. Source: The Journal of Clinical Psychiatry. 1991 August; 52(8): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1907963&dopt=Abstract
•
Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients. Author(s): Kavoussi RJ, Segraves RT, Hughes AR, Ascher JA, Johnston JA. Source: The Journal of Clinical Psychiatry. 1997 December; 58(12): 532-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9448656&dopt=Abstract
94
Bupropion
•
Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. Author(s): Feighner J, Hendrickson G, Miller L, Stern W. Source: Journal of Clinical Psychopharmacology. 1986 February; 6(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3081600&dopt=Abstract
•
Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain. Author(s): Semenchuk MR, Sherman S, Davis B. Source: Neurology. 2001 November 13; 57(9): 1583-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706096&dopt=Abstract
•
Drug safety without borders: concerns about bupropion. Author(s): Mintzes B, Bassett K, Wright JM. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 September 3; 167(5): 447. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240797&dopt=Abstract
•
Drug-induced rash with eosinophilia and systemic symptoms syndrome with bupropion administration. Author(s): Bagshaw SM, Cload B, Gilmour J, Leung ST, Bowen TJ. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 May; 90(5): 572-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775141&dopt=Abstract
•
ECG conduction delays associated with massive bupropion overdose. Author(s): Paris PA, Saucier JR. Source: Journal of Toxicology. Clinical Toxicology. 1998; 36(6): 595-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9776964&dopt=Abstract
•
Economic model of sustained-release bupropion hydrochloride in health plan and work site smoking-cessation programs. Author(s): Halpern MT, Khan ZM, Young TL, Battista C. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2000 August 1; 57(15): 1421-9. Erratum In: Am J Health Syst Pharm 2000 October 1; 57(19): 1803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10938982&dopt=Abstract
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Effect of bupropion on chocolate craving. Author(s): Michell GF, Mebane AH, Billings CK. Source: The American Journal of Psychiatry. 1989 January; 146(1): 119-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2492163&dopt=Abstract
Studies
95
•
Effect of bupropion on dopamine and 5-hydroxytryptamine-mediated behaviour in mice. Author(s): Muley MP, Joshi MA, Manekar MS. Source: The Journal of Pharmacy and Pharmacology. 1984 March; 36(3): 208-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6144762&dopt=Abstract
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Effect of bupropion on immunodensity of putative imidazoline receptors on platelets of depressed patients. Author(s): Zhu H, Halaris A, Madakasira S, Pazzaglia P, Goldman N, DeVane CL, Andrew M, Reis D, Piletz JE. Source: Journal of Psychiatric Research. 1999 July-August; 33(4): 323-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10404470&dopt=Abstract
•
Effect of bupropion-SR on orgasmic dysfunction in nondepressed subjects: a pilot study. Author(s): Modell JG, May RS, Katholi CR. Source: Journal of Sex & Marital Therapy. 2000 July-September; 26(3): 231-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10929571&dopt=Abstract
•
Effect of bupropion-SR on REM sleep: relationship to antidepressant response. Author(s): Ott GE, Rao U, Nuccio I, Lin KM, Poland RE. Source: Psychopharmacology. 2002 December; 165(1): 29-36. Epub 2002 November 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474115&dopt=Abstract
•
Effect of plasma from patients containing bupropion and its metabolites on the uptake of norepinephrine. Author(s): Perumal AS, Smith TM, Suckow RF, Cooper TB. Source: Neuropharmacology. 1986 February; 25(2): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3084990&dopt=Abstract
•
Effect on body weight of bupropion sustained-release in patients with major depression treated for 52 weeks. Author(s): Croft H, Houser TL, Jamerson BD, Leadbetter R, Bolden-Watson C, Donahue R, Metz A. Source: Clinical Therapeutics. 2002 April; 24(4): 662-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017410&dopt=Abstract
•
Effects of bupropion on body weight. Author(s): Harto-Truax N, Stern WC, Miller LL, Sato TL, Cato AE. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406454&dopt=Abstract
96
Bupropion
•
Effects of bupropion SR on anterior paralimbic function during waking and REM sleep in depression: preliminary findings using. Author(s): Nofzinger EA, Berman S, Fasiczka A, Miewald JM, Meltzer CC, Price JC, Sembrat RC, Wood A, Thase ME. Source: Psychiatry Research. 2001 April 10; 106(2): 95-111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306249&dopt=Abstract
•
Effects of bupropion sustained-release on sexual functioning and nocturnal erections in healthy men. Author(s): Labbate LA, Brodrick PS, Nelson RP, Lydiard RB, Arana GW. Source: Journal of Clinical Psychopharmacology. 2001 February; 21(1): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199957&dopt=Abstract
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Effects of bupropion, nomifensine and dexamphetamine on performance, subjective feelings, autonomic variables and electroencephalogram in healthy volunteers. Author(s): Hamilton MJ, Smith PR, Peck AW. Source: British Journal of Clinical Pharmacology. 1983 March; 15(3): 367-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6405773&dopt=Abstract
•
Effects of cocaine prior to and during bupropion maintenance in cocaine-abusing volunteers. Author(s): Oliveto A, McCance-Katz FE, Singha A, Petrakis I, Hameedi F, Kosten TR. Source: Drug and Alcohol Dependence. 2001 July 1; 63(2): 155-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11376920&dopt=Abstract
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Effects of gender on relapse prevention in smokers treated with bupropion SR. Author(s): Gonzales D, Bjornson W, Durcan MJ, White JD, Johnston JA, Buist AS, Sachs DP, Rigotti NA, Niaura R, Hays JT, Hurt RD. Source: American Journal of Preventive Medicine. 2002 May; 22(4): 234-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11988379&dopt=Abstract
•
Effects of rapid tryptophan depletion on sleep electroencephalogram and mood in subjects with partially remitted depression on bupropion. Author(s): Evans L, Golshan S, Kelsoe J, Rapaport M, Resovsky K, Sutton L, Gillin JC. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 December; 27(6): 1016-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464458&dopt=Abstract
Studies
97
•
Effects of steady-state bupropion on the pharmacokinetics of lamotrigine in healthy subjects. Author(s): Odishaw J, Chen C. Source: Pharmacotherapy. 2000 December; 20(12): 1448-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130217&dopt=Abstract
•
Effects of sustained-release bupropion and supportive group therapy on cigarette consumption in patients with schizophrenia. Author(s): Weiner E, Ball MP, Summerfelt A, Gold J, Buchanan RW. Source: The American Journal of Psychiatry. 2001 April; 158(4): 635-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11282701&dopt=Abstract
•
Efficacy and safety of bupropion SR for smoking cessation: data from clinical trials and five years of postmarketing experience. Author(s): Ferry L, Johnston JA. Source: Int J Clin Pract. 2003 April; 57(3): 224-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723728&dopt=Abstract
•
Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism. Author(s): Hayford KE, Patten CA, Rummans TA, Schroeder DR, Offord KP, Croghan IT, Glover ED, Sachs DP, Hurt RD. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1999 February; 174: 173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211174&dopt=Abstract
•
Efficacy of bupropion in tricyclic-resistant or intolerant patients. Author(s): Stern WC, Harto-Truax N, Bauer N. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406447&dopt=Abstract
•
Efficacy of sustained-release bupropion in neuropathic pain: an open-label study. Author(s): Semenchuk MR, Davis B. Source: The Clinical Journal of Pain. 2000 March; 16(1): 6-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741812&dopt=Abstract
•
Electroconvulsive therapy in a depressed patient receiving bupropion. Author(s): Figiel GS, Jarvis MR. Source: Journal of Clinical Psychopharmacology. 1990 October; 10(5): 376. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2124220&dopt=Abstract
98
Bupropion
•
Elevated P-selectin on platelets in depression: response to bupropion. Author(s): Piletz JE, Zhu H, Madakasira S, Pazzaglia P, Lindsay DeVane C, Goldman N, Halaris A. Source: Journal of Psychiatric Research. 2000 November-December; 34(6): 397-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165307&dopt=Abstract
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Enantiomeric determination of the phenylmorpholinol metabolite of bupropion in human plasma using coupled achiral-chiral liquid chromatography. Author(s): Suckow RF, Zhang MF, Cooper TB. Source: Biomedical Chromatography : Bmc. 1997 May-June; 11(3): 174-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192113&dopt=Abstract
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Eosinophilia associated with bupropion. Author(s): Malesker MA, Soori GS, Malone PM, Mahowald JA, Housel GJ. Source: The Annals of Pharmacotherapy. 1995 September; 29(9): 867-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8547734&dopt=Abstract
•
Erythema multiforme associated with bupropion use. Author(s): Carrillo-Jimenez R, Zogby M, Treadwell TL. Source: Archives of Internal Medicine. 2001 June 25; 161(12): 1556. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427106&dopt=Abstract
•
Evaluation of bupropion hydrochloride: the first of a new class of atypical antidepressants. Author(s): Preskorn SH, Othmer SC. Source: Pharmacotherapy. 1984 January-February; 4(1): 20-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6422449&dopt=Abstract
•
Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment. Author(s): Segraves RT, Kavoussi R, Hughes AR, Batey SR, Johnston JA, Donahue R, Ascher JA. Source: Journal of Clinical Psychopharmacology. 2000 April; 20(2): 122-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770448&dopt=Abstract
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Evaluation of the contribution of cytochrome P450 3A4 to human liver microsomal bupropion hydroxylation. Author(s): Faucette SR, Hawke RL, Shord SS, Lecluyse EL, Lindley CM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 August; 29(8): 1123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454731&dopt=Abstract
Studies
99
•
Evaluation of the safety and efficacy of bupropion in depression. Author(s): Halaris AE, Stern WC, Van Wyck Fleet J, Reno RM. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406435&dopt=Abstract
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Excretion of bupropion in breast milk. Author(s): Briggs GG, Samson JH, Ambrose PJ, Schroeder DH. Source: The Annals of Pharmacotherapy. 1993 April; 27(4): 431-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8477117&dopt=Abstract
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Failure of bupropion to affect prolactin or growth hormone in man. Author(s): Whiteman PD, Peck AW, Fowle AS, Smith PR. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 209-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406460&dopt=Abstract
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Failure of bupropion to affect the response to tyramine in man. Author(s): Fowle AS, Peck AW, Rogers HJ, Spector RG. Source: British Journal of Clinical Pharmacology. 1981 July; 12(1): 86-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6788059&dopt=Abstract
•
Failure of bupropion to affect tyramine response in man. Author(s): Fowle AS, Peck AW, Rogers HJ, Spector RG. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406461&dopt=Abstract
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Falling backward in two elderly patients taking bupropion. Author(s): Szuba MP, Leuchter AF. Source: The Journal of Clinical Psychiatry. 1992 May; 53(5): 157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1592841&dopt=Abstract
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Fatal bupropion overdose. Author(s): Harris CR, Gualtieri J, Stark G. Source: Journal of Toxicology. Clinical Toxicology. 1997; 35(3): 321-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9140330&dopt=Abstract
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Fluoxetine and bupropion treatment of bipolar disorder, type II, associated with GAD. Author(s): Novac A. Source: The Journal of Clinical Psychiatry. 1992 February; 53(2): 67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1541607&dopt=Abstract
100
Bupropion
•
Generalized pustular and erythrodermic psoriasis associated with bupropion treatment. Author(s): Cox NH, Gordon PM, Dodd H. Source: The British Journal of Dermatology. 2002 June; 146(6): 1061-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072078&dopt=Abstract
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Ileus as a possible result of bupropion in an elderly woman. Author(s): Kales HC, Mellow AM. Source: The Journal of Clinical Psychiatry. 1999 May; 60(5): 337. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10362444&dopt=Abstract
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Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. Author(s): Walker PW, Cole JO, Gardner EA, Hughes AR, Johnston JA, Batey SR, Lineberry CG. Source: The Journal of Clinical Psychiatry. 1993 December; 54(12): 459-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8276736&dopt=Abstract
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Incidence of seizures during treatment with tricyclic antidepressant drugs and bupropion. Author(s): Peck AW, Stern WC, Watkinson C. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 197-201. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406457&dopt=Abstract
•
Increased rate of trazodone prescribing with bupropion and selective serotoninreuptake inhibitors versus tricyclic antidepressants. Author(s): Clark NA, Alexander B. Source: The Annals of Pharmacotherapy. 2000 September; 34(9): 1007-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10981245&dopt=Abstract
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Influence of bupropion HCl (Wellbatrin), a novel antidepressant, on plasma levels of prolactin and growth hormone in man and rat. Author(s): Stern WC, Rogers J, Fang V, Meltzer H. Source: Life Sciences. 1979 November 12; 25(20): 1717-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=316848&dopt=Abstract
•
Interaction of intra-articular steroids and bupropion. Author(s): White P. Source: Clinical Radiology. 2002 March; 57(3): 235. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952327&dopt=Abstract
Studies
101
•
Is bupropion (Zyban) causing deaths? Author(s): Chapman SC, Jamrozik K. Source: The Medical Journal of Australia. 2002 February 4; 176(3): 134. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936312&dopt=Abstract
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Is erythema multiforme associated with bupropion use? Author(s): Drago F, Rebora A. Source: Archives of Internal Medicine. 2002 April 8; 162(7): 843. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926865&dopt=Abstract
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Lack of effect of cimetidine on the pharmacokinetics of sustained-release bupropion. Author(s): Kustra R, Corrigan B, Dunn J, Duncan B, Hsyu PH. Source: Journal of Clinical Pharmacology. 1999 November; 39(11): 1184-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10579150&dopt=Abstract
•
Lack of efficacy of a new antidepressant (bupropion) in the treatment of panic disorder with phobias. Author(s): Sheehan DV, Davidson J, Manschreck T, Van Wyck Fleet J. Source: Journal of Clinical Psychopharmacology. 1983 February; 3(1): 28-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6403599&dopt=Abstract
•
Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Author(s): Jamerson BD, Nides M, Jorenby DE, Donahue R, Garrett P, Johnston JA, Fiore MC, Rennard SI, Leischow SJ. Source: Clinical Therapeutics. 2001 May; 23(5): 744-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394732&dopt=Abstract
•
Long-term efficacy and safety of bupropion. Author(s): Othmer E, Othmer SC, Stern WC, Van Wyck Fleet J. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406448&dopt=Abstract
•
Long-term preventive care in depression: the use of bupropion in patients intolerant of other antidepressants. Author(s): Gardner EA. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 157-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406449&dopt=Abstract
102
Bupropion
•
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
•
Mania in an elderly man treated with bupropion. Author(s): Bittman BJ, Young RC. Source: The American Journal of Psychiatry. 1991 April; 148(4): 541. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1900981&dopt=Abstract
•
Mania with bupropion: a dose-related phenomenon? Author(s): Goren JL, Levin GM. Source: The Annals of Pharmacotherapy. 2000 May; 34(5): 619-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852090&dopt=Abstract
•
Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion. Author(s): Horst WD, Preskorn SH. Source: Journal of Affective Disorders. 1998 December; 51(3): 237-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10333980&dopt=Abstract
•
Mediating mechanisms for the impact of bupropion in smoking cessation treatment. Author(s): Lerman C, Roth D, Kaufmann V, Audrain J, Hawk L, Liu A, Niaura R, Epstein L. Source: Drug and Alcohol Dependence. 2002 July 1; 67(2): 219-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095672&dopt=Abstract
•
Menstrual irregularities associated with bupropion treatment. Author(s): Halbreich U, Rojansky N, Bakhai Y, Wang K. Source: The Journal of Clinical Psychiatry. 1991 January; 52(1): 15-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1899086&dopt=Abstract
•
Metabolism and kinetics of bupropion. Author(s): Schroeder DH. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 79-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406469&dopt=Abstract
Studies
103
•
Metabolism of some “second”- and “fourth”-generation antidepressants: iprindole, viloxazine, bupropion, mianserin, maprotiline, trazodone, nefazodone, and venlafaxine. Author(s): Rotzinger S, Bourin M, Akimoto Y, Coutts RT, Baker GB. Source: Cellular and Molecular Neurobiology. 1999 August; 19(4): 427-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10379419&dopt=Abstract
•
Methodologic approach to adverse events applied to bupropion clinical trials. Author(s): Cato AE, Cook L, Starbuck R, Heatherington D. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 187-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406455&dopt=Abstract
•
Naturalistic, self-assignment comparative trial of bupropion SR, a nicotine patch, or both for smoking cessation treatment in primary care. Author(s): Gold PB, Rubey RN, Harvey RT. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2002 Fall; 11(4): 315-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584874&dopt=Abstract
•
Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking. Author(s): Hurt RD, Krook JE, Croghan IT, Loprinzi CL, Sloan JA, Novotny PJ, Kardinal CG, Knost JA, Tirona MT, Addo F, Morton RF, Michalak JC, Schaefer PL, Porter PA, Stella PJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 1; 21(5): 914-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610193&dopt=Abstract
•
Nicotine reduction and bupropion. Author(s): Neumann JK, Peeples B, Seneker A. Source: Chest. 2002 April; 121(4): 1378. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948088&dopt=Abstract
•
Nicotine reduction: effectiveness of bupropion. Author(s): Neumann JK, Peeples B, East J, Ellis AR. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2000 July; 177: 87-8. Erratum In: Br J Psychiatry 2000 November; 177: 471. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945100&dopt=Abstract
104
Bupropion
•
Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine. Author(s): Fryer JD, Lukas RJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 January; 288(1): 88-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9862757&dopt=Abstract
•
Nortriptyline toxicity secondary to interaction with bupropion sustained-release. Author(s): Weintraub D. Source: Depression and Anxiety. 2001; 13(1): 50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233461&dopt=Abstract
•
Omission of bupropion as a recommended treatment for PTSD. Author(s): Reeves RM. Source: The Journal of Clinical Psychiatry. 2000 October; 61(10): 786. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11078042&dopt=Abstract
•
Ondansetron rather than metoclopramide for bupropion-induced nausea. Author(s): Lara DR, Busnello ED, Souza DO. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 May; 46(4): 371. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11387797&dopt=Abstract
•
Open-label pilot study of bupropion plus bromocriptine for treatment of cocaine dependence. Author(s): Montoya ID, Preston KL, Rothman R, Gorelick DA. Source: The American Journal of Drug and Alcohol Abuse. 2002; 28(1): 189-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853133&dopt=Abstract
•
Organic mental disorders associated with bupropion in three patients. Author(s): Ames D, Wirshing WC, Szuba MP. Source: The Journal of Clinical Psychiatry. 1992 February; 53(2): 53-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1541606&dopt=Abstract
•
Overview of clinically significant adverse reactions to bupropion. Author(s): Van Wyck Fleet J, Manberg PJ, Miller LL, Harto-Truax N, Sato T, Fleck RJ, Stern WC, Cato AE. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406456&dopt=Abstract
Studies
105
•
Panic associated with combining fluoxetine and bupropion. Author(s): Young SJ. Source: The Journal of Clinical Psychiatry. 1996 April; 57(4): 177-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8601558&dopt=Abstract
•
Paroxetine/bupropion combination treatment for refractory depression. Author(s): Marshall RD, Liebowitz MR. Source: Journal of Clinical Psychopharmacology. 1996 February; 16(1): 80-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8834426&dopt=Abstract
•
Perceptual changes with bupropion, a novel antidepressant. Author(s): Becker RE, Dufresne RL. Source: The American Journal of Psychiatry. 1982 September; 139(9): 1200-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6810715&dopt=Abstract
•
Pharmacokinetic interactions between cyclosporine and bupropion or methylphenidate. Author(s): Lewis BR, Aoun SL, Bernstein GA, Crow SJ. Source: Journal of Child and Adolescent Psychopharmacology. 2001 Summer; 11(2): 1938. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11436960&dopt=Abstract
•
Pharmacokinetic optimisation of sustained-release bupropion for smoking cessation. Author(s): Johnston AJ, Ascher J, Leadbetter R, Schmith VD, Patel DK, Durcan M, Bentley B. Source: Drugs. 2002; 62 Suppl 2: 11-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109932&dopt=Abstract
•
Pharmacokinetics of bupropion and its major basic metabolites in normal subjects after a single dose. Author(s): Laizure SC, DeVane CL, Stewart JT, Dommisse CS, Lai AA. Source: Clinical Pharmacology and Therapeutics. 1985 November; 38(5): 586-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3931955&dopt=Abstract
•
Pharmacokinetics of bupropion and its metabolites in cigarette smokers versus nonsmokers. Author(s): Hsyu PH, Singh A, Giargiari TD, Dunn JA, Ascher JA, Johnston JA. Source: Journal of Clinical Pharmacology. 1997 August; 37(8): 737-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9378846&dopt=Abstract
106
Bupropion
•
Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects. Author(s): Findlay JW, Van Wyck Fleet J, Smith PG, Butz RF, Hinton ML, Blum MR, Schroeder DH. Source: European Journal of Clinical Pharmacology. 1981; 21(2): 127-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6804243&dopt=Abstract
•
Pharmacokinetics of second generation antidepressants: bupropion. Author(s): Goodnick PJ. Source: Psychopharmacology Bulletin. 1991; 27(4): 513-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1813898&dopt=Abstract
•
Pharmacokinetics of single- and multiple-dose bupropion in elderly patients with depression. Author(s): Sweet RA, Pollock BG, Kirshner M, Wright B, Altieri LP, DeVane CL. Source: Journal of Clinical Pharmacology. 1995 September; 35(9): 876-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8786247&dopt=Abstract
•
Pharmacological significance of the species differences in bupropion metabolism. Author(s): Welch RM, Lai AA, Schroeder DH. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1987 March; 17(3): 287-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3107223&dopt=Abstract
•
Place of bupropion in smoking-cessation therapy. Author(s): Silagy C, Formica N. Source: Lancet. 2001 May 19; 357(9268): 1550. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377641&dopt=Abstract
•
Possible bupropion precipitation of mania and a mixed affective state. Author(s): Zubieta JK, Demitrack MA. Source: Journal of Clinical Psychopharmacology. 1991 October; 11(5): 327-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1765576&dopt=Abstract
•
Preclinical toxicology of bupropion: an overview. Author(s): Tucker WE Jr. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 60-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406465&dopt=Abstract
Studies
107
•
Prevalence of psychosis, delusions, and hallucinations in clinical trials with bupropion. Author(s): Johnston JA, Lineberry CG, Frieden CS. Source: The American Journal of Psychiatry. 1986 September; 143(9): 1192-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3092682&dopt=Abstract
•
Priapism associated with bupropion treatment. Author(s): Levenson JL. Source: The American Journal of Psychiatry. 1995 May; 152(5): 813. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7726332&dopt=Abstract
•
Private practice evaluation of the safety and efficacy of bupropion in depressed outpatients. Author(s): Kirksey DF, Harto-Truax N. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 143-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406446&dopt=Abstract
•
Psychopharmacology of bupropion in normal volunteers. Author(s): Peck AW, Hamilton M. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 202-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406458&dopt=Abstract
•
Psychoses associated with bupropion treatment. Author(s): Golden RN, James SP, Sherer MA, Rudorfer MV, Sack DA, Potter WZ. Source: The American Journal of Psychiatry. 1985 December; 142(12): 1459-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3934991&dopt=Abstract
•
Radioimmunoassay and pharmacokinetic profile of bupropion in the dog. Author(s): Butz RF, Schroeder DH, Welch RM, Mehta NB, Phillips AP, Findlay JW. Source: The Journal of Pharmacology and Experimental Therapeutics. 1981 June; 217(3): 602-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6785419&dopt=Abstract
•
Radioimmunoassay for bupropion in human plasma: comparison of tritiated and iodinated radioligands. Author(s): Butz RF, Smith PG, Schroeder DH, Findlay JW. Source: Clinical Chemistry. 1983 March; 29(3): 462-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6402324&dopt=Abstract
108
Bupropion
•
Recreational bupropion abuse in a teenager. Author(s): McCormick J. Source: British Journal of Clinical Pharmacology. 2002 February; 53(2): 214. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851650&dopt=Abstract
•
Relationship between drug exposure and the efficacy and safety of bupropion sustained release for smoking cessation. Author(s): Johnston JA, Fiedler-Kelly J, Glover ED, Sachs DP, Grasela TH, DeVeaughGeiss J. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 May; 3(2): 131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403727&dopt=Abstract
•
REM sleep enhancement by bupropion in depressed men. Author(s): Nofzinger EA, Reynolds CF 3rd, Thase ME, Frank E, Jennings JR, Fasiczka AL, Sullivan LR, Kupfer DJ. Source: The American Journal of Psychiatry. 1995 February; 152(2): 274-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7840365&dopt=Abstract
•
Remission of Crohn's disease on bupropion. Author(s): Kast RE, Altschuler EL. Source: Gastroenterology. 2001 November; 121(5): 1260-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706830&dopt=Abstract
•
Response in relation to baseline anxiety levels in major depressive disorder treated with bupropion sustained release or sertraline. Author(s): Rush AJ, Trivedi MH, Carmody TJ, Donahue RM, Houser TL, Bolden-Watson C, Batey SR, Ascher JA, Metz A. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 July; 25(1): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377926&dopt=Abstract
•
Retrospective analysis of the health-care costs of bupropion sustained release in comparison with other antidepressants. Author(s): Poret AW, Neslusan C, Ricci JF, Wang S, Khan ZM, Kwong JW. Source: Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2001 September-October; 4(5): 362-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705126&dopt=Abstract
Studies
109
•
Reversal of atypical depression, sleepiness, and REM-sleep propensity in narcolepsy with bupropion. Author(s): Rye DB, Dihenia B, Bliwise DL. Source: Depression and Anxiety. 1998; 7(2): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9614600&dopt=Abstract
•
Reversible dyskinesia during bupropion therapy. Author(s): Gardos G. Source: The Journal of Clinical Psychiatry. 1997 May; 58(5): 218. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9184616&dopt=Abstract
•
Review of bupropion for smoking cessation. Author(s): Richmond R, Zwar N. Source: Drug and Alcohol Review. 2003 June; 22(2): 203-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850907&dopt=Abstract
•
Review of bupropion. Author(s): Bryant SG, Guernsey BG, Ingrim NB. Source: Clin Pharm. 1983 November-December; 2(6): 525-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6140095&dopt=Abstract
•
Review of placebo-controlled trials with bupropion. Author(s): Zung WW. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 104-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406436&dopt=Abstract
•
Rhabdomyolysis associated with bupropion treatment. Author(s): David D, Esquenazi J. Source: Journal of Clinical Psychopharmacology. 1999 April; 19(2): 185-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211923&dopt=Abstract
•
Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Author(s): Hesse LM, von Moltke LL, Shader RI, Greenblatt DJ. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 February; 29(2): 100-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159797&dopt=Abstract
110
Bupropion
•
Safety and efficacy of bupropion in elderly patients: preliminary observations. Author(s): Kane JM, Cole K, Sarantakos S, Howard A, Borenstein M. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 134-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406442&dopt=Abstract
•
Safety profile of bupropion for chronic obstructive pulmonary disease. Author(s): Campbell IA. Source: Lancet. 2001 September 22; 358(9286): 1010. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586980&dopt=Abstract
•
Safety profile of bupropion for chronic obstructive pulmonary disease. Author(s): Cox A, Anton C. Source: Lancet. 2001 September 22; 358(9286): 1010. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586979&dopt=Abstract
•
Safety profile of bupropion for chronic obstructive pulmonary disease. Author(s): Garcia-Rio F, Serrano S, Mediano O, Alonso A, Villamor J. Source: Lancet. 2001 September 22; 358(9286): 1009-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586978&dopt=Abstract
•
Safety profile of sustained-release bupropion in depression: results of three clinical trials. Author(s): Settle EC, Stahl SM, Batey SR, Johnston JA, Ascher JA. Source: Clinical Therapeutics. 1999 March; 21(3): 454-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10321415&dopt=Abstract
•
Seizure after guanfacine plus bupropion: correction. Author(s): Tilton P. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2000 November; 39(11): 1341. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11068884&dopt=Abstract
•
Seizure and cardiac arrest during bupropion SR treatment. Author(s): Bergmann F, Bleich S, Wischer S, Paulus W. Source: Journal of Clinical Psychopharmacology. 2002 December; 22(6): 630-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454568&dopt=Abstract
Studies
111
•
Seizure associated with bupropion and guanfacine. Author(s): Namerow LB. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1999 January; 38(1): 2-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9893404&dopt=Abstract
•
Seizure associated with sleep deprivation and sustained-release bupropion. Author(s): Oncken CA, Duckrow RB. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 131-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745515&dopt=Abstract
•
Seizure during combination of trimipramine and bupropion. Author(s): Enns MW. Source: The Journal of Clinical Psychiatry. 2001 June; 62(6): 476-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465529&dopt=Abstract
•
Seizure induced by insufflation of bupropion. Author(s): Welsh CJ, Doyon S. Source: The New England Journal of Medicine. 2002 September 19; 347(12): 951. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239274&dopt=Abstract
•
Seizures and bupropion: a review. Author(s): Davidson J. Source: The Journal of Clinical Psychiatry. 1989 July; 50(7): 256-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2500425&dopt=Abstract
•
Serum bupropion levels in 2 breastfeeding mother-infant pairs. Author(s): Baab SW, Peindl KS, Piontek CM, Wisner KL. Source: The Journal of Clinical Psychiatry. 2002 October; 63(10): 910-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416600&dopt=Abstract
•
Serum sickness induced by bupropion. Author(s): Yolles JC, Armenta WA, Alao AO. Source: The Annals of Pharmacotherapy. 1999 September; 33(9): 931-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10492492&dopt=Abstract
112
Bupropion
•
Serum sickness-like reaction with bupropion. Author(s): Peloso PM, Baillie C. Source: Jama : the Journal of the American Medical Association. 1999 November 17; 282(19): 1817. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10573271&dopt=Abstract
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Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment. Author(s): Coleman CC, Cunningham LA, Foster VJ, Batey SR, Donahue RM, Houser TL, Ascher JA. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1999 December; 11(4): 205-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10596735&dopt=Abstract
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Sexual function in patients taking bupropion sustained release. Author(s): Segraves RT, Segraves KB, Bubna CN. Source: The Journal of Clinical Psychiatry. 1995 August; 56(8): 374. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7635855&dopt=Abstract
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Short-term effectiveness of bupropion for assisting smoking cessation in general practice. Author(s): Zwar NA, Nasser A, Comino EJ, Richmond RL. Source: The Medical Journal of Australia. 2002 September 2; 177(5): 277-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197829&dopt=Abstract
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Should bupropion dosage be adjusted based upon therapeutic drug monitoring? Author(s): Preskorn SH. Source: Psychopharmacology Bulletin. 1991; 27(4): 637-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1813908&dopt=Abstract
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Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking status and gender. Author(s): Stewart JJ, Berkel HJ, Parish RC, Simar MR, Syed A, Bocchini JA Jr, Wilson JT, Manno JE. Source: Journal of Clinical Pharmacology. 2001 July; 41(7): 770-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452710&dopt=Abstract
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Smoking cessation: the role of bupropion among new pharmacologic agents. Author(s): Nardini S. Source: Monaldi Arch Chest Dis. 2001 October; 56(5): 467-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887507&dopt=Abstract
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Speed of onset of action of the newer antidepressants--fluoxetine and bupropion. Author(s): George MS, Lydiard RB. Source: International Clinical Psychopharmacology. 1991 Winter; 6(4): 209-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1840065&dopt=Abstract
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Splitting bupropion extended-release tablets. Author(s): Cochren BE. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 March 15; 56(6): 575. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10192696&dopt=Abstract
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Spontaneous orgasm with the combined use of bupropion and sertraline. Author(s): Grimes JB, Labbate LA. Source: Biological Psychiatry. 1996 December 1; 40(11): 1184-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8931924&dopt=Abstract
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SSRIs, bupropion, and sexual function. Author(s): Edens N, Newton WP. Source: The Journal of Family Practice. 1997 August; 45(2): 101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9267363&dopt=Abstract
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Stability of bupropion and its major metabolites in human plasma. Author(s): Laizure SC, DeVane CL. Source: Therapeutic Drug Monitoring. 1985; 7(4): 447-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3936237&dopt=Abstract
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Substitution of an SSRI with bupropion sustained release following SSRI-induced sexual dysfunction. Author(s): Clayton AH, McGarvey EL, Abouesh AI, Pinkerton RC. Source: The Journal of Clinical Psychiatry. 2001 March; 62(3): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305705&dopt=Abstract
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Sustained release bupropion: overdose and treatment. Author(s): White RS, Langford JR. Source: The American Journal of Emergency Medicine. 2002 July; 20(4): 388-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098206&dopt=Abstract
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Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. a randomized, controlled trial. Author(s): Hays JT, Hurt RD, Rigotti NA, Niaura R, Gonzales D, Durcan MJ, Sachs DP, Wolter TD, Buist AS, Johnston JA, White JD. Source: Annals of Internal Medicine. 2001 September 18; 135(6): 423-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560455&dopt=Abstract
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Sustained-release bupropion for selective serotonin reuptake inhibitor-induced sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel-group study. Author(s): Masand PS, Ashton AK, Gupta S, Frank B. Source: The American Journal of Psychiatry. 2001 May; 158(5): 805-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11329407&dopt=Abstract
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Sustained-release bupropion for smoking cessation in African Americans: a randomized controlled trial. Author(s): Ahluwalia JS, Harris KJ, Catley D, Okuyemi KS, Mayo MS. Source: Jama : the Journal of the American Medical Association. 2002 July 24-31; 288(4): 468-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132977&dopt=Abstract
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Sustained-release bupropion for smoking cessation. Author(s): Pasternak M. Source: The New England Journal of Medicine. 1998 February 26; 338(9): 619-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9480439&dopt=Abstract
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Sustained-release bupropion overdose: a new entity for Australian emergency departments. Author(s): Paoloni R, Szekely I. Source: Emergency Medicine (Fremantle, W.A.). 2002 March; 14(1): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11993828&dopt=Abstract
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The cardiovascular effects of bupropion and nortriptyline in depressed outpatients. Author(s): Kiev A, Masco HL, Wenger TL, Johnston JA, Batey SR, Holloman LC. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1994 June; 6(2): 107-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7804386&dopt=Abstract
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The cardiovascular profile of bupropion. Author(s): Wenger TL, Stern WC. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 176-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406453&dopt=Abstract
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The clinical effectiveness and cost-effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation. Author(s): Woolacott NF, Jones L, Forbes CA, Mather LC, Sowden AJ, Song FJ, Raftery JP, Aveyard PN, Hyde CJ, Barton PM. Source: Health Technology Assessment (Winchester, England). 2002; 6(16): 1-245. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269277&dopt=Abstract
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The combined use of bupropion, lithium, and venlafaxine during ECT: a case of prolonged seizure activity. Author(s): Conway CR, Nelson LA. Source: The Journal of Ect. 2001 September; 17(3): 216-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528316&dopt=Abstract
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The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses. Author(s): Posner J, Bye A, Dean K, Peck AW, Whiteman PD. Source: European Journal of Clinical Pharmacology. 1985; 29(1): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3932079&dopt=Abstract
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The effect of bupropion on nicotine craving and withdrawal. Author(s): Shiffman S, Johnston JA, Khayrallah M, Elash CA, Gwaltney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J. Source: Psychopharmacology. 2000 January; 148(1): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10663415&dopt=Abstract
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The effect of bupropion on prolactin in a patient with a pituitary microadenoma. Author(s): Harsch HH. Source: Psychopharmacology. 1987; 92(3): 402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3114793&dopt=Abstract
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The effect of bupropion sustained-release on cigarette craving after smoking cessation. Author(s): Durcan MJ, Deener G, White J, Johnston JA, Gonzales D, Niaura R, Rigotti N, Sachs DP. Source: Clinical Therapeutics. 2002 April; 24(4): 540-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017399&dopt=Abstract
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The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man. Author(s): Hamilton MJ, Bush MS, Peck AW. Source: European Journal of Clinical Pharmacology. 1984; 27(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6436033&dopt=Abstract
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The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Author(s): Hamilton MJ, Bush M, Smith P, Peck AW. Source: British Journal of Clinical Pharmacology. 1982 December; 14(6): 791-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6817770&dopt=Abstract
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The efficacy of bupropion in winter depression: results of an open trial. Author(s): Dilsaver SC, Qamar AB, Del Medico VJ. Source: The Journal of Clinical Psychiatry. 1992 July; 53(7): 252-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1639745&dopt=Abstract
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The impact of bupropion on psychomotor performance. Author(s): Paul MA, Gray G, Kenny G, Lange M. Source: Aviation, Space, and Environmental Medicine. 2002 November; 73(11): 1094-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433233&dopt=Abstract
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The lack of effect of bupropion HCL (Wellbatrin) on the secretion of growth hormone and prolactin in humans. Author(s): Laakmann G, Hoffmann N, Hofschuster E. Source: Life Sciences. 1982 May 17; 30(20): 1725-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6124859&dopt=Abstract
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The pharmacologic basis for therapeutic interest in bupropion. Author(s): Soroko FE, Maxwell RA. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406467&dopt=Abstract
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The pharmacology underlying pharmacotherapy for tobacco dependence: a focus on bupropion. Author(s): Balfour DJ. Source: Int J Clin Pract. 2001 January-February; 55(1): 53-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219320&dopt=Abstract
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The rise of serum aminotransferases in a patient treated with bupropion. Author(s): Oslin DW, Duffy K. Source: Journal of Clinical Psychopharmacology. 1993 October; 13(5): 364-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8227497&dopt=Abstract
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The use of bupropion hydrochloride for smoking cessation therapy. Author(s): Nichols MR. Source: Clin Excell Nurse Pract. 1999 November; 3(6): 317-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865568&dopt=Abstract
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The use of bupropion in hospitalized depressed patients. Author(s): Merideth CH, Feighner JP. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 85-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406471&dopt=Abstract
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The use of bupropion in the treatment of restlessness after a traumatic brain injury. Author(s): Teng CJ, Bhalerao S, Lee Z, Farber J, Morris H, Foran T, Tucker W. Source: Brain Injury : [bi]. 2001 May; 15(5): 463-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350660&dopt=Abstract
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Therapeutic drug monitoring of bupropion. Author(s): Preskorn SH, Fleck RJ, Schroeder DH. Source: The American Journal of Psychiatry. 1990 December; 147(12): 1690-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2123082&dopt=Abstract
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Therapeutic effectiveness of bupropion for bulimia: a possible artifact. Author(s): Hahn WK. Source: The Journal of Clinical Psychiatry. 1989 May; 50(5): 188. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2497100&dopt=Abstract
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Three fatal drug overdoses involving bupropion. Author(s): Friel PN, Logan BK, Fligner CL. Source: Journal of Analytical Toxicology. 1993 November-December; 17(7): 436-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8309220&dopt=Abstract
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Tinnitus related to bupropion treatment. Author(s): Settle EC Jr. Source: The Journal of Clinical Psychiatry. 1991 August; 52(8): 352. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1907965&dopt=Abstract
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Tissue distribution of bupropion in a fatal overdose. Author(s): Rohrig TP, Ray NG. Source: Journal of Analytical Toxicology. 1992 September-October; 16(5): 343-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1294844&dopt=Abstract
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Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Author(s): Aubin HJ. Source: Drugs. 2002; 62 Suppl 2: 45-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109935&dopt=Abstract
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Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study. Author(s): McIntyre RS, Mancini DA, McCann S, Srinivasan J, Sagman D, Kennedy SH. Source: Bipolar Disorders. 2002 June; 4(3): 207-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180276&dopt=Abstract
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Treatment of atopic dermatitis and psoriasis vulgaris with bupropion-SR: a pilot study. Author(s): Modell JG, Boyce S, Taylor E, Katholi C. Source: Psychosomatic Medicine. 2002 September-October; 64(5): 835-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271115&dopt=Abstract
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Treatment of bulimia with bupropion: a multicenter controlled trial. Author(s): Horne RL, Ferguson JM, Pope HG Jr, Hudson JI, Lineberry CG, Ascher J, Cato A. Source: The Journal of Clinical Psychiatry. 1988 July; 49(7): 262-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3134343&dopt=Abstract
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Treatment of fluoxetine-induced sexual dysfunction with bupropion: a case report. Author(s): Labbate LA, Pollack MH. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1994 March; 6(1): 13-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7951639&dopt=Abstract
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Treatment of headache with bupropion. Author(s): Pinsker W. Source: Headache. 1998 January; 38(1): 58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9505009&dopt=Abstract
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Treatment of smokeless tobacco addiction with bupropion and behavior modification. Author(s): Berigan TR, Deagle EA 3rd. Source: Jama : the Journal of the American Medical Association. 1999 January 20; 281(3): 233. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9918477&dopt=Abstract
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Treatment of social phobia with bupropion. Author(s): Emmanuel NP, Lydiard RB, Ballenger JC. Source: Journal of Clinical Psychopharmacology. 1991 August; 11(4): 276-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1918431&dopt=Abstract
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Two multicenter studies of the antidepressant effects of bupropion HCl versus placebo. Author(s): Stern WC, Harto-Truax N. Source: Psychopharmacology Bulletin. 1980 July; 16(3): 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6773096&dopt=Abstract
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Use of bupropion in patients who exhibit orthostatic hypotension on tricyclic antidepressants. Author(s): Farid FF, Wenger TL, Tsai SY, Singh BN, Stern WC. Source: The Journal of Clinical Psychiatry. 1983 May; 44(5 Pt 2): 170-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6406451&dopt=Abstract
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Use of bupropion SR in a pharmacist-managed outpatient smoking-cessation program. Author(s): Roth MT, Westman EC. Source: Pharmacotherapy. 2001 May; 21(5): 636-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349752&dopt=Abstract
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Use of bupropion with SRIs and venlafaxine. Author(s): Spier SA. Source: Depression and Anxiety. 1998; 7(2): 73-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9614595&dopt=Abstract
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Use of sustained-release bupropion in specific patient populations for smoking cessation. Author(s): Tonstad S. Source: Drugs. 2002; 62 Suppl 2: 37-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109934&dopt=Abstract
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Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Author(s): Faucette SR, Hawke RL, Lecluyse EL, Shord SS, Yan B, Laethem RM, Lindley CM. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2000 October; 28(10): 1222-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997944&dopt=Abstract
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Venlafaxine and bupropion combination therapy in a case of treatment-resistant depression. Author(s): Fatemi SH, Emamian ES, Kist DA. Source: The Annals of Pharmacotherapy. 1999 June; 33(6): 701-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10410184&dopt=Abstract
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Venlafaxine but not bupropion decreases cerebrospinal fluid 5-hydroxyindoleacetic acid in unipolar depression. Author(s): Little JT, Ketter TA, Mathe AA, Frye MA, Luckenbaugh D, Post RM. Source: Biological Psychiatry. 1999 February 1; 45(3): 285-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10023503&dopt=Abstract
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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
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Visual and auditory hallucinations with the association of bupropion and valproate. Author(s): Filteau MJ, Leblanc J, Lefrancoise S, Demers MF. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2000 March; 45(2): 198-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10742884&dopt=Abstract
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Zyban-- is there a cause for concern? Author(s): Tracey JA. Source: Expert Opinion on Drug Safety. 2002 November; 1(4): 303-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904129&dopt=Abstract
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CHAPTER 2. NUTRITION AND BUPROPION Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and bupropion.
Finding Nutrition Studies on Bupropion 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 “bupropion” (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.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “bupropion” (or a synonym): •
A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. Author(s): Center for Tobacco Research and Intervention, University of Wisconsin Medical School, Madison, USA. Source: Jorenby, D E Leischow, S J Nides, M A Rennard, S I Johnston, J A Hughes, A R Smith, S S Muramoto, M L Daughton, D M Doan, K Fiore, M C Baker, T B N-Engl-JMed. 1999 March 4; 340(9): 685-91 0028-4793
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Amfebutamone/bupropion for smoking cessation: new preparation. Nicotine replacement therapy is safer. Source: Anonymous Prescrire-Int. 2001 December; 10(56): 163-7 1167-7422
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Antidepressant profile of bupropion and three metabolites in mice. Author(s): Departement de Pharmacologie, Faculte de Medicine Pite-Salpetriere, Paris, France. Source: Martin, P Massol, J Colin, J N Lacomblez, L Puech, A J Pharmacopsychiatry. 1990 July; 23(4): 187-94 0176-3679
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Ask the doctor. I am trying to help my husband stop smoking. He tried to use the antidepressant Zyban, but it didn't work. He has also tried the nicotine patch, and that didn't work either. Is there any reason why he shouldn't try both together? Source: Lee, T H Harv-Heart-Lett. 1999 June; 9(10): 8 1051-5313
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Bupropion as a promising approach to rapid cycling bipolar II patients. Author(s): Mood Disorders Program, Charter Lakeside Hospital, Memphis, TN. Source: Haykal, R F Akiskal, H S J-Clin-Psychiatry. 1990 November; 51(11): 450-5 01606689
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Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women. Author(s): Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA.
[email protected] Source: Gadde, K M Parker, C B Maner, L G Wagner, H R 2nd Logue, E J Drezner, M K Krishnan, K R Obes-Res. 2001 September; 9(9): 544-51 1071-7323
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Bupropion hydrochloride: the development of a chiral separation using an ovomucoid column. Author(s): Atrix Laboratories, Fort Collins, CO 80525-4417, USA. Source: Munro, J S Walker, T A J-Chromatogr-A. 2001 April 13; 913(1-2): 275-82
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Bupropion inhibits nicotine-evoked [(3)H]overflow from rat striatal slices preloaded with [(3)H]dopamine and from rat hippocampal slices preloaded with [(3)H]norepinephrine. Author(s): College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA. Source: Miller, D K Sumithran, S P Dwoskin, L P J-Pharmacol-Exp-Ther. 2002 September; 302(3): 1113-22 0022-3565
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Bupropion occupancy of the dopamine transporter is low during clinical treatment. Author(s): Department of Psychiatry, PET Centre, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada.
[email protected] Source: Meyer, J H Goulding, V S Wilson, A A Hussey, D Christensen, B K Houle, S Psychopharmacology-(Berl). 2002 August; 163(1): 102-5 0033-3158
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Bupropion or patch for smoking cessation? Author(s):
[email protected] Source: Kane, K Y Ellis, M R J-Fam-Pract. 1999 June; 48(6): 419 0094-3509
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Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial. Author(s): Department of Internal Medicine, Veterans Affairs Medical Center, University of Kentucky, Lexington, Kentucky, USA.
[email protected] Source: Anderson, J W Greenway, F L Fujioka, K Gadde, K M McKenney, J O'Neil, P M Obes-Res. 2002 July; 10(7): 633-41 1071-7323
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Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms. Author(s): Medical Research Institute, Slidell, Louisiana, USA.
[email protected] Source: Jain, A K Kaplan, R A Gadde, K M Wadden, T A Allison, D B Brewer, E R Leadbetter, R A Richard, N Haight, B Jamerson, B D Buaron, K S Metz, A Obes-Res. 2002 October; 10(10): 1049-56 1071-7323
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Bupropion SR worsens mood during marijuana withdrawal in humans. Author(s): Division on Substance Abuse, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York 10032, USA.
[email protected] Source: Haney, M Ward, A S Comer, S D Hart, C L Foltin, R W Fischman, M W Psychopharmacology-(Berl). 2001 May; 155(2): 171-9 0033-3158
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Bupropion sustained release and smoking cessation. Author(s): Miriam Hospital and Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, RI 02906, USA. Source: Goldstein, M G J-Clin-Psychiatry. 1998; 59 Suppl 466-72 0160-6689
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Clinical efficacy of bupropion in the management of smoking cessation. Author(s): Department of Medicine, Center for Tobacco Research and Intervention, University of Wisconsin Medical School, 1930 Monroe Street, Madison, WI 53711, USA.
[email protected] Source: Jorenby, Douglas Drugs. 2002; 62 Suppl 2: 25-35 0012-6667
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Cost-benefit analysis of sustained-release bupropion, nicotine patch, or both for smoking cessation. Author(s): Global Health Outcomes, Glaxo Wellcome Inc., Research Triangle Park, North Carolina 27709-3398, USA.
[email protected] Source: Nielsen, K Fiore, M C Prev-Med. 2000 March; 30(3): 209-16 0091-7435
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Differential regulation of dopamine transporter after chronic self-administration of bupropion and nomifensine. Author(s): Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007-2195, USA. Source: Tella, S R Ladenheim, B Cadet, J L J-Pharmacol-Exp-Ther. 1997 April; 281(1): 508-13 0022-3565
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Effects of cocaine prior to and during bupropion maintenance in cocaine-abusing volunteers. Author(s): Department of Psychiatry, Yale School of Medicine, New Haven, CT 06519, USA.
[email protected] Source: Oliveto, A McCance Katz, F E Singha, A Petrakis, I Hameedi, F Kosten, T R Drug-Alcohol-Depend. 2001 July 1; 63(2): 155-67 0376-8716
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Investigating the actions of bupropion on dependence-related effects of nicotine in rats. Author(s): Section of Behavioural Pharmacology, Institute of Psychiatry, Kings College London, De Crespigny Park, London SE5 8AF, UK.
[email protected] Source: Shoaib, M Sidhpura, N Shafait, S Psychopharmacology-(Berl). 2003 February; 165(4): 405-12 0033-3158
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Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Author(s): Clinical Development Depression/Dependence, Medical Affairs, GlaxoSmithKline, Research Triangle Park, North Carolina 27709-3398, USA.
[email protected] Source: Jamerson, B D Nides, M Jorenby, D E Donahue, R Garrett, P Johnston, J A Fiore, M C Rennard, S I Leischow, S J Clin-Ther. 2001 May; 23(5): 744-52 0149-2918
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Nicotine and bupropion share a similar discriminative stimulus effect. Author(s): Department of Medicinal Chemistry, School of Pharmacy, Box 980540, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
[email protected] Source: Young, R Glennon, R A Eur-J-Pharmacol. 2002 May 17; 443(1-3): 113-8 0014-2999
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Nicotine-like discriminative stimulus effects of bupropion in rats. Author(s): Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond 23298-0613, USA.
[email protected] Source: Wiley, J L Lavecchia, K L Martin, B R Damaj, M I Exp-Clin-Psychopharmacol. 2002 May; 10(2): 129-35 1064-1297
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Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine. Author(s): Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA. Source: Fryer, J D Lukas, R J J-Pharmacol-Exp-Ther. 1999 January; 288(1): 88-92 00223565
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Open-label pilot study of bupropion plus bromocriptine for treatment of cocaine dependence. Author(s): Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Source: Montoya, Ivan D Preston, Kenzie L Rothman, Richard Gorelick, David A Am-JDrug-Alcohol-Abuse. 2002; 28(1): 189-96 0095-2990
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The clinical effectiveness and cost-effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation. Author(s): NHS Center for Reviews and Dissemination, University of York, UK Source: Woolacott, N F Jones, L Forbes, C A Mather, L C Sowden, A J Song, F J Raftery, J P Aveyard, P N Hyde, C J Barton, P M Health-Technol-Assess. 2002; 6(16): 1-245 13665278
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The effect of bupropion on nicotine craving and withdrawal. Author(s): Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
[email protected] Source: Shiffman, S Johnston, J A Khayrallah, M Elash, C A Gwaltney, C J Paty, J A Gnys, M Evoniuk, G DeVeaugh Geiss, J Psychopharmacology-(Berl). 2000 January; 148(1): 33-40 0033-3158
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Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Author(s): Centre de Traitement des Addictions, Hopital Emile Roux, 1 Avenue de Verdun, 94456 Limeil-Brevannes, France.
[email protected] Source: Aubin, Henri Jean Drugs. 2002; 62 Suppl 2: 45-52 0012-6667
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
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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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/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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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
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND BUPROPION Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to bupropion. 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 bupropion 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 “bupropion” (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 bupropion: •
A comparison of bupropion hydrochloride with dexamphetamine and amitriptyline in healthy subjects. Author(s): Peck AW, Bye CE, Clubley M, Henson T, Riddington C. Source: British Journal of Clinical Pharmacology. 1979 May; 7(5): 469-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=475943&dopt=Abstract
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Alternative therapies for bipolar disorder. Author(s): Lerer B. Source: The Journal of Clinical Psychiatry. 1985 August; 46(8): 309-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3926754&dopt=Abstract
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Antidepressants for smoking cessation: a promising new approach? Author(s): Huibers MJ, Chavannes NH, Wagena EJ, van Schayck CP.
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Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 September; 16(3): 379-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11028646&dopt=Abstract •
Behavioral evidence implicating dopamine in sensorimotor arousal and norepinephrine in the sedative effects of antidepressant drugs. Author(s): Kokkinidis L, McCarter BD. Source: Psychopharmacology. 1990; 100(4): 542-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2320716&dopt=Abstract
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Bupropion occupancy of the dopamine transporter is low during clinical treatment. Author(s): Meyer JH, Goulding VS, Wilson AA, Hussey D, Christensen BK, Houle S. Source: Psychopharmacology. 2002 August; 163(1): 102-5. Epub 2002 July 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185406&dopt=Abstract
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Bupropion SR worsens mood during marijuana withdrawal in humans. Author(s): Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW. Source: Psychopharmacology. 2001 May; 155(2): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401006&dopt=Abstract
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Deficient sensorimotor gating after 6-hydroxydopamine lesion of the rat medial prefrontal cortex is reversed by haloperidol. Author(s): Koch M, Bubser M. Source: The European Journal of Neuroscience. 1994 December 1; 6(12): 1837-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7704295&dopt=Abstract
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Effects of bupropion SR on anterior paralimbic function during waking and REM sleep in depression: preliminary findings using. Author(s): Nofzinger EA, Berman S, Fasiczka A, Miewald JM, Meltzer CC, Price JC, Sembrat RC, Wood A, Thase ME. Source: Psychiatry Research. 2001 April 10; 106(2): 95-111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306249&dopt=Abstract
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Effects of smoked marijuana in healthy and HIV + marijuana smokers. Author(s): Haney M. Source: Journal of Clinical Pharmacology. 2002 November; 42(11 Suppl): 34S-40S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412834&dopt=Abstract
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Ephedrine and other stimulants as ergogenic aids. Author(s): Bohn AM, Khodaee M, Schwenk TL.
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Source: Curr Sports Med Rep. 2003 August; 2(4): 220-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834578&dopt=Abstract •
Evidence for the involvement of dopamine in ambulation promoted by menthol in mice. Author(s): Umezu T, Morita M. Source: Journal of Pharmacological Sciences. 2003 February; 91(2): 125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686756&dopt=Abstract
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Impact of over-the-counter sales on effectiveness of pharmaceutical aids for smoking cessation. Author(s): Pierce JP, Gilpin EA. Source: Jama : the Journal of the American Medical Association. 2002 September 11; 288(10): 1260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215133&dopt=Abstract
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Pharmacotherapy of nicotine dependence. Author(s): Haustein KO. Source: Int J Clin Pharmacol Ther. 2000 June; 38(6): 273-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890576&dopt=Abstract
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Recent advances in the pharmacotherapy of smoking. Author(s): Hughes JR, Goldstein MG, Hurt RD, Shiffman S. Source: Jama : the Journal of the American Medical Association. 1999 January 6; 281(1): 72-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9892454&dopt=Abstract
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Variations in treatment benefits influence smoking cessation: results of a randomised controlled trial. Author(s): Schauffler HH, McMenamin S, Olson K, Boyce-Smith G, Rideout JA, Kamil J. Source: Tobacco Control. 2001 June; 10(2): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11387540&dopt=Abstract
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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
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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/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to bupropion; 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 (some Web sites are subscription based): •
General Overview Depression Source: Healthnotes, Inc. www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com
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Herbs and Supplements Antidepressants Source: Healthnotes, Inc. www.healthnotes.com Bupropion Source: Healthnotes, Inc. www.healthnotes.com
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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.
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CHAPTER 4. DISSERTATIONS ON BUPROPION Overview In this chapter, we will give you a bibliography on recent dissertations relating to bupropion. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “bupropion” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bupropion, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Bupropion ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to bupropion. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Bupropion Sustained-release As an Intervention for Tobacco Cessation: Examining Its Addition to an Established Program by Cardwell, Everett Rollie (buddy), Jr. Psyd from Spalding University, 2002, 67 pages http://wwwlib.umi.com/dissertations/fullcit/3065639
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND BUPROPION Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning bupropion.
Recent Trials on Bupropion The following is a list of recent trials dedicated to bupropion.8 Further information on a trial is available at the Web site indicated. •
A Program to Quit Smoking With or Without Bupropion in Treating Patients With Stage I or II Non-Small Cell Lung Cancer Who Have Undergone Surgery Condition(s): Non-small cell lung cancer; stage I non-small cell lung cancer; stage II nonsmall cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI); Cancer and Leukemia Group B; Eastern Cooperative Oncology Group Purpose - Excerpt: RATIONALE: A program that includes bupropion may be more effective in helping early-stage lung cancer patients to quit smoking. It is not yet known if a program to quit smoking is more effective with or without bupropion. PURPOSE: Randomized phase III trial to determine the effectiveness of a program to quit smoking with or without bupropion in treating patients who have undergone surgery for stage I or stage II non-small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032084
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These are listed at www.ClinicalTrials.gov.
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Bupropion and Weight Control for Smoking Cessation - 1 Condition(s): Tobacco Use Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: Smoking Cessation for Women Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006170
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Bupropion as a Smoking Cessation Aid in Alcoholics Condition(s): Alcoholism; Smoking Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: The purpose of this study is to test the use of time-released bupropion (Wellbutrin) in patients receiving treatment for alcohol abuse/dependence as an aid to stop smoking. Patients will receive either a time-released bupropion or placebo. Both groups will receive nicotine replacement therapy during the 9 week study. A final followup assessment will be conducted 6 months from the start of treatment. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044434
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Combinations of Pharmacologic Smoking Cessation Treatments Condition(s): Smoking Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The purpose of this study is to test the effectiveness of a combination of the drugs bupropion and mecamylamine along with a nicotine patch as a therapy for smoking cessation. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018187
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Drug Treatment for Pathological Gambling Condition(s): Gambling Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH)
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Purpose - Excerpt: The purpose of the study is to determine whether the drug bupropion is an effective treatment for Pathological Gambling (PG). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055393 •
Facilitating Implementation of the PHS Smoking Cessation Guideline Condition(s): Smoking Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: The adverse impact of tobacco use on disease prevalence and health care costs is well documented. Hence, finding effective ways to reduce tobacco dependence is an essential component of improving the outcomes, quality and efficiency of VHA care. The U.S. Public Health Service (PHS) Smoking Cessation Clinical Practice Guideline provides specific recommendations for treating tobacco dependence. Despite their strong evidence base, however, these recommendations have not been fully integrated into clinical practice within the VHA. Recent data suggest that logistical difficulties associated with identifying and linking smokers with appropriate treatments may explain why the PHS Smoking Cessation Guideline has not been more broadly implemented. The primary objective of this study is to assess the effectiveness of an intervention for increasing the rate of tobacco dependence treatment in a population of smokers identified through the VA Pharmacy Benefits Management database. Secondary objectives of this study include (1) assessing the effect of the intervention on smoking cessation rates, and (2) developing options for overcoming potential barriers to broad implementation of the strategies. The effectiveness of the intervention will be evaluated using a multi-center, randomized, controlled trial. Veterans receiving a prescription for transdermal nicotine, nicotine gum, or bupropion for smoking cessation in the past year at one of the participating VHA facilities (as determined from Pharmacy Benefits Management records) will be eligible for the study. A total of 2,400 eligible veterans selected from eight test sites will be randomly assigned to one of two groups: (1) patient phone call and tailored, computerized prompt to providers (intervention), or (2) usual care (control). The primary outcome is the proportion of patients receiving pharmacological or other smoking cessation treatment in the six month follow-up period, as assessed from VA pharmacy and outpatient data files. All patients will be recruited to a brief phone interview six months postintervention to gather secondary outcome measure data related to smoking status, quit history, and use of smoking cessation assistance. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057070
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Pilot study examining the effects of combined pharmacotherapy (Zyban/NRT)/behavioral treatment on smoking cessation among MMT patients. - 2 Condition(s): Tobacco Use Disorder Study Status: This study is currently recruiting patients.
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Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: Pilot study examining the effects of combined pharmacotherapy (Zyban/NRT)/behavioral treatment on smoking cessation among MMT patients. Phase(s): Phase II Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060814 •
Platelet Function in Patients Treated with SSRI and non-SSRI Antidepressants Condition(s): Depression Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will examine the effect of a class of antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) on platelet function. Platelets are small blood cells that help stop bleeding after injury to a blood vessel by forming a clot, or plug, in the vessel. Some medications impair platelet function, leading to increased bruising and bleeding. SSRIs decrease an important platelet component called serotonin, which may cause bleeding in some patients. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox) and citalopram (Celexa). Patients 18 years of age and older being treated for depression with a SSRI or the non-SSRI bupropion (Wellbutrin) may be eligible for this study. Subjects will be recruited from a private clinic in Washington, D.C. Participants will provide a history of their current medications and past history of bleeding. They will have about 4 tablespoons of blood drawn for tests to measure blood cell counts and platelet function. The study takes about 1 hour. The results of the SSRI-treated group and the bupropiontreated group will be analyzed and compared. This study may provide information that will help health care providers make treatment decisions to minimize possible adverse effects of medications in patients with depression. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009568
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Treatment of Adolescents with Comorbid Alcohol Use and Attention Deficit Hyperactivity Disorder (bupropion) Condition(s): Alcoholism; Attention Deficit Hyperactivity Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: This study will compare the effectiveness of sustained release bupropion (Wellbutrin) versus a placebo in the treatment of adolescents with comorbid alcohol use disorder and attention deficit hyperactivity disorder. Adolescents, ages 1418 will be recruited from community treatment programs for a 16-week trial with follow-up assessments. Phase(s): Phase II Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029614 •
Double-Blind, Placebo-Controlled Assessment of Potential Interactions Between IV Methamphetamine and Oral Bupropion - 1 Condition(s): Amphetamine-Related Disorders Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute on Drug Abuse (NIDA); University of California, Los Angeles Purpose - Excerpt: Double-Blind, Placebo-Controlled Assessment of Potential Interactions Between IV Methamphetamine and Oral Bupropion Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040040
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Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression Condition(s): Bipolar Disorder; Depressive Disorder Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will compare the effectiveness of relatively new antidepressants which have different mechanisms of action. Buproprion (Wellbutrin) works on dopamine and the dopaminergic pathway. Sertraline (Zoloft) works as a selective serotonin reuptake inhibitor (SSRI). Venlafaxine (Effexor) works as a mixed serotonin, norepinephrine, and dopamine reuptake inhibitor. Subjects enrolled in this study will be patients diagnosed with a bipolar disorder who are presently taking medication to prevent the symptoms of the disease (prophylactic treatment), but have had breakthrough episodes of depression despite taking their medication. Patients will receive any one of the three antidepressant medications as noted above plus a placebo inactive sugar pill, in order to mask which antidepressant is being prescribed) in addition to their regular medication for bipolar disorder. All of the doses will be calculated as effective for the treatment of a unipolar major depressive disorder. The patient will continue receiving the medication for ten weeks. The effectiveness of the drug treatment will be measured by using three different scales; 1. Inventory for Depressive Symptoms - Clinicians form (IDS-C) 2. Clinical Global Impression scale(CGIBP) 3. Life Charting Methodology (LCM) Patients who do not respond to their medication within ten weeks from the beginning of the study will be considered as nonresponders and be offered the opportunity to start the study again, taking one of the two remaining medications. For example, if a patient was assigned to take Wellbutrin but it was ineffective, he/she could re-enter the study and be given either Zoloft or Effexor. Patients that do respond in the first ten weeks of the study will be eligible to continue taking the medication for one year to assess the long term effectiveness of the drug on preventing episodes of depression and to assess for any possible differential induction of mania. Phase(s): Phase II Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001483 •
Pharmacologic Relapse Prevention for Alcoholic Smokers Condition(s): Alcoholism; Smoking Study Status: This study is completed. Sponsor(s): National Institute on Alcohol Abuse and Alcoholism (NIAAA) Purpose - Excerpt: This study will compare the long-term use of bupropion (Wellbutrin) and placebo for reducing the rate of smoking relapse in recovering alcoholics who achieved initial abstinence from smoking with nicotine patch therapy. The study will also determine the cessation rate in the 8th week of treatment among recovering alcoholics using a nicotine patch. The patch dose is projected to serve as a 100-percent replacement. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000457
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 “bupropion” (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/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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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
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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
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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
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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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/
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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
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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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
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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
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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
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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
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CHAPTER 6. PATENTS ON BUPROPION 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 “bupropion” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bupropion, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Bupropion By performing a patent search focusing on bupropion, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on bupropion: •
Apparatus and method for transdermal delivery of bupropion Inventor(s): Junginer; Hans E. (Leiden, NL), Midha; Kamal K. (Hamilton, BM), Hirsh; Mark (Wellesley, MA) Assignee(s): Pierce Management, LLC (Wellesley, MA) Patent Number: 6,280,763 Date filed: May 10, 1999 Abstract: The invention includes an apparatus and method for transdermal delivery of bupropion base. In the method of this invention, patient is administered parenterally a bupropion base in an amount effective to alleviate withdrawal symptoms and to prevent or reduce craving of nicotine in said patient. Alternatively, an effective amount of bupropion base is delivered to alleviate depression in a patient. A transdermal delivery system includes a bupropion base. The bupropion base can be mixed with an acceptable pharmaceutical carrier. Excerpt(s): Bupropion hydrochloride is a known antidepressant sold in instant release tablet form under the brand names Wellbutkin.RTM. and Zyban.RTM.. Bupropion hydrochloride is an antidepressant of the aminoketone class and is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitors or other known antidepressant agents. Bupropion (BUP) hydrochloride is highly metabolized in both rats and humans. The major metabolites are the erythroamino alcohol (EB), the threoamino alcohol (TB), and the hydroxy metabolite (HB). The metabolites exhibit pharmacological activity in an antitetrabenzene model. Bupropion hydrochloride is also useful in preventing functional impairment and drowsiness seen upon administration of benzodiazepine, in the treatment of minimal brain dysfunction, tardive dyskinesia, impaired mental alertness upon ingestion of ethanol and psychosexual dysfunction. While the instant release tablets currently sold are suitable for the indicated use, there is a disadvantage to bupropion hydrochloride in that there can be an accumulation of metabolites that can be detrimental to one's health.... In a study of pharmacokinetics of bupropion hydrochloride in the elderly, six elderly patients with diagnosed depression were examined in a single and multiple dose study. Half-lives (t1/2app) of the metabolites TB, EB, and HB were 38.8+/-7.6 hours, 61.4+/-21.6 hours, and 34.2+/-4.6 hours, respectively. After multiple dosing, the half-life for bupropion and its metabolites did not change significantly, although in some patients the half-life of metabolites was substantially prolonged. In addition, there was also evidence of inordinate accumulation of metabolites. The elderly are at risk for accumulation of bupropion and its metabolites. See J Clin. Pharmacol. 35:876-884 (1995).... Therefore, a need exists for a new form of bupropion for delivering to the body while minimizing the formation of metabolites. Web site: http://www.delphion.com/details?pn=US06280763__
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Bupropion metabolites and methods of use Inventor(s): Fang; Qun K. (Wellesley, MA), McCullough; John R. (Hudson, MA), Jerussi; Thomas P. (Framingham, MA), Senanayake; Chrisantha H. (Shrewsbury, MA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 6,342,496 Date filed: February 22, 2000 Abstract: Methods are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, cerebral function disorders, cigarette smoking, and incontinence. Excerpt(s): This invention relates to synthesis of, methods of using, and compositions comprising bupropion metabolites and isomers thereof.... Bupropion, a racemic mixture of (+)- and (-)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone, is an antidepressant of the aminoketone class, and is described in U.S. Pat. Nos. 3,819,706 and 3,885,046. The hydrochloride salt of bupropion is sold under the trade names WELLBUTRIN.RTM. and WELLBUTRIN SR.RTM. for the treatment of depression. Bupropion is also sold under the trade name ZYBAN.RTM. as a drug useful to achieve smoking cessation. Additional benefits of bupropion maleate are reported in European Patent Application No. 118036.... Although its mechanism of action is poorly understood, bupropion is reportedly a weak but selective inhibitor of dopamine. Its potency as an inhibitor of norepinephrine reuptake is reportedly only half of that for dopamine, and it shows little affinity for the serotonergic transport system. Ascher, J. A., et al., J Clin. Psychiatry, 56:395-401 (1995). Web site: http://www.delphion.com/details?pn=US06342496__
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Bupropion to treat herpes viral diseases Inventor(s): Reindler; Christopher William (Como, AU) Assignee(s): CC Capital Partners Inc. (Toronto, CA) Patent Number: 6,512,011 Date filed: January 11, 2002 Abstract: Methods are disclosed for the treatment of a herpes viral infection in a human or animal subject by administering bupropion or a physiologically acceptable salt, solvate or enantiomer thereof. Most particularly, the virus is HSV1 or HSV2. Excerpt(s): This invention relates to a new medical use for bupropion and physiologically acceptable salts and solvates thereof. Specifically the invention concerns the use of bupropion in treating viral infections, more particularly infections caused by viruses of the Herpes family.... Bupropion hydrochloride, (.+-.)-1-(3-chlorophenyl)-2[(1,1-di-methylethyl)-amino]-1-propanone hydrochloride has been used for the treatment of depression. Bupropion is a relatively weak inhibitor of the neuronal uptake of noradrenaline (NA), serotonin and dopamine (DA), and does not inhibit monoamine oxidase. While the mechanism of action of bupropion, as with other antidepressants, is unknown, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. Available evidence suggests that bupropion is a selective inhibitor of noradrenaline (NA) at doses that are predictive of antidepressant activity in animal models. See Ascher, J. A., et al., Bupropion: A Review of its Mechanism of Antidepressant Activity. Journal of Clinical Psychiatry, 56: p. 395-401,1995.... It has also
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been disclosed that bupropion is useful for the treatment of migraine (U.S. Pat. No. 5,753,712), reducing cholesterol (U.S. Pat. No. 4,438,138), treatment of minimal brain dysfunction (U.S. Pat. No. 4,435,449), treatment of tardive dyskinesia (U.S. Pat. No. 4,425,363), reversing impaired mental alertness due to ethanol consumption (U.S. Pat. No. 4,393,078), treatment of psychosexual dysfunction (U.S. Pat. No. 4,507,323), suppressing prolactin secretion (U.S. Pat. No. 4,347,257) and as an aid to smoking cessation. Web site: http://www.delphion.com/details?pn=US06512011__ •
Controlled release bupropion formulation Inventor(s): Xie; Jianbo (Davie, FL), Chen; Chih-Ming (Davie, FL), Jan; Steve (Coral Springs, FL) Assignee(s): Andrx Pharmaceuticals, Inc. (Fort Lauderdale, FL) Patent Number: 6,210,716 Date filed: February 26, 1999 Abstract: A controlled release dosage form of bupropion hydrochloride which comprises:(a) a first pellet having a core of bupropion hydrochloride and hydroxypropyl methylcellulose at a weight ratio of 10:1 to 30:1 and a coating of a mixture of an acrylic resin which is soluble in acidic media and ethyl cellulose;(b) a second pellet having a core of bupropion hydrochloride and hydroxypropyl methylcellulose at a ratio of 10:1 to 30:1; an inner coating of a mixture of an acrylic resin which is soluble in acidic media and a water insoluble polymer and an outer coating which comprises an enteric coating polymer. Excerpt(s): The present invention relates to a controlled release formulation of bupropion hydrochloride. The compound bupropion hydrochloride is described in U.S. Pat. No. 3,819,706 as an antidepressant.... U.S. Pat. No. 5,427,798 describes a controlled release formulation of bupropion which based on a ratio of hydroxypropyl methylcellulose which is 1 part of bupropion to 0.19 to 1.1 parts of hydroxypropyl methylcellulose. U.S. Pat. No. 5,358,970 discloses a formulation of bupropion hydrochloride which is stabilized with a stabilizer which has specific acid properties under particular test conditions. RE 33,994 is limited to a bupropion hydrochloride controlled release formulation which releases 10-45% of bupropion hydrochloride within two hours; 25-70% bupropion hydrochloride within 4 hours and 40-90% of bupropion hydrochloride within six hours. Wellbutrin SR is a commercially available twice a day dosage form of bupropion hydrochloride which contains carnauba wax, cysteine hydrochloride, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol and titanium dioxide.... The applicants have discovered that a two pellet controlled release formulation may be employed to provide a dosage formulation which has a controlled release profile which is bioequivalent to Wellbutrin SR but has a distinctly different in vitro release profile than Wellbutrin SR. Web site: http://www.delphion.com/details?pn=US06210716__
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Controlled release tablet of bupropion hydrochloride Inventor(s): Seth; Pawan (Irvine, CA) Assignee(s): Pharma Pass LLC (Irvine, CA) Patent Number: 6,033,686 Date filed: October 30, 1998 Abstract: The invention provides a controlled release tablet, free of stabilizer and free of pore-forming agent comprising: (i) a core consisting essentially of bupropion hydrochloride, a binder and a lubricant; and (ii) a coating consisting essentially of a water-insoluble, water-permeable film-forming polymer, a plasticizer and a watersoluble polymer. Excerpt(s): Bupropion (its salt hydrochloride) is a widely used antidepressant drug. A commercial example is Wellbutrin.RTM.. This product consists in immediate release tablet, 75 or 100 mg strength. However it has been proven that bupropion hydrochloride can induce some severe side effects. For example, seizures can occur in about 0.4% patients and this effect has been proven to be related with immediate release tablets because of the peak in bupropion plasmatic concentration induced by such a dosage form. The development of a new sustained release dosage form has therefore been considered as an appropriate means to overcome this situation.... U.S. Pat. No. 5,358,970 and U.S. Pat. No. 5,427,798, both to Burroughs Wellcome, describe a sustained release formulation of bupropion hydrochloride based on matrix technology. The term matrix refers to a tablet where the drug is embedded in an excipient that makes a nondisintegrating core called matrix. Drug diffusion occurs through this core. As bupropion hydrochloride is unstable, the product described in the above two patents requires a stabilizer to achieve sufficient stability. This stabilizer is an acidic compound, preferably cysteine hydrochloride. Matrix technology is however not suited for the manufacture of a tablet, since it implies the use of a stabilizer.... U.S. Pat. No. 4,687,660 and EP-A0171457 disclose a tablet formed of a core and a coating, where the core comprises bupropion hydrochloride together with excipient(s) and optionally an osmotic enhancing agent and where the coating comprises a water-insoluble, water-permeable film-forming polymer (such as cellulose acetate), a pore-forming agent (such as impalpable lactose and sodium carbonate), and optionally a so-called waterpermeability enhancing agent (such as polyethyleneglycol) and again optionally a plasticizer. This type of coating, since it requires pore-forming agent, cannot provide a uniform coating and therefore the release rate cannot be uniform from one tablet to another. Web site: http://www.delphion.com/details?pn=US06033686__
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Controlled sustained release tablets containing bupropion Inventor(s): Bass, Jr. William L. (Farmville, NC), Ludwig; Jennie Sue G. (Greenville, NC), Sutton, Jr. Joel E. (Greenville, NC) Assignee(s): Burroughs Wellcome Co. (Research Triangle Park, NC) Patent Number: 5,427,798 Date filed: August 12, 1993 Abstract: A controlled sustained release tablet having at least one year shelf life and containing bupropion hydrochloride, hydroxypropyl methylcellulose and cysteine
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hydrochloride or glycine hydrochloride with the tablet having a surface area to volume ratio to effectively control bupropion hydrochloride release in the body. Excerpt(s): Bupropion hydrochloride (Wellbutrin.RTM.) is a marketed antidepressant. It is chemically known as (.+-.)-2-(tert-butylamino)-3'-chloropropiophenone hydrochloride. (See U.S. Pat. Nos. 3,819,706 and 3,885,046 and the Merck Index, Eleventh Edition, entry No. 1488).... In usage, bupropion hydrochloride is sold in the form of an instant release tablet wherein greater than 75% of bupropion hydrochloride is released from the tablet into dissolution media in 45 minutes (See 1993 Physicians Desk Reference (PDR), pages 842 to 844). The PDR indicates bupropion hydrochloride as presently sold in an instant release tablet as being associated with seizures in approximately 0.4% (4/1000) patients treated at doses of up to 450 mg per day. In studies to date, the risk of seizures seem to be strongly associated, in part, with use of instant release tablets.... In order to reduce the seizure rate, it has been determined after experimentation that a controlled sustained release of bupropion hydrochloride should be employed. Web site: http://www.delphion.com/details?pn=US05427798__ •
Cyclodextrin stabilized pharmaceutical compositions of bupropion hydrochloride Inventor(s): Gidwani; Suresh Kumar (Mumbai, IN), Singnurkar; Purushottam (Mumbai, IN), Tewari; Prashant Kumar (Mumbai, IN) Assignee(s): USV Limited (Mumbai, IN) Patent Number: 6,462,237 Date filed: June 14, 2001 Abstract: An inclusion complex of bupropion hydrochloride with beta cyclodextrin that stabilizes the bupropion hydrochloride against degradation. A method of preparing an inclusion complex of bupropion hydrochloride with beta cyclodextrin that stabilizes the bupropion hydrochloride against degradation. A novel stabilized sustained-release pharmaceutical composition of bupropion hydrochloride containing an inclusion complex of bupropion hydrochloride with beta cyclodextrin. A method of preparing a novel stabilized sustained-release pharmaceutical composition containing an inclusion complex of bupropion hydrochloride with beta cyclodextrin. Excerpt(s): The present invention relates to a stabilized sustained-release pharmaceutical composition of bupropion hydrochloride containing an inclusion complex of bupropion hydrochloride with beta cyclodextrin. The invention also relates to the preparation of a stabilized sustained release pharmaceutical compositions of bupropion hydrochloride containing the inclusion complex of bupropion hydrochloride with beta cyclodextrin.... The invention further relates to a method for preventing the degradation of bupropion hydrochloride by making an inclusion complex with beta cyclodextrin, thus allowing the preparation of acceptable pharmaceutical compositions for sustained release tablets and capsules.... Bupropion hydrochloride is an antidepressant of the aminoketone class. It is designated as (.+-.)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propane hydrochloride. Bupropion hydrochloride has been shown to decompose in variety of pharmaceutical compositions formulated without the use of stabilizer. Web site: http://www.delphion.com/details?pn=US06462237__
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Delayed release coated tablet of bupropion hydrochloride Inventor(s): Seth; Pawan (Irvine, CA) Assignee(s): Pharma Pass LLC (Irvine, CA) Patent Number: 6,143,327 Date filed: December 13, 1999 Abstract: The invention provides a delayed release coated tablet, free of stabilizer and free of pore-forming agent comprising: (i) a core consisting essentially of bupropion hydrochloride, a binder and a lubricant; and (ii) a first coating consisting essentially of a water-insoluble, water-permeable film-forming polymer, a plasticizer and a watersoluble polymer; and (iii) a second coating consisting essentially of a methacrylic polymer and a plasticizer therefor. Excerpt(s): Bupropion (its salt hydrochloride) is a widely used antidepressant drug. A commercial example is Wellbutrin.RTM.. This product consists in immediate release tablet, 75 or 100 mg strength. However it has been proven that bupropion hydrochloride can induce some severe side effects. For example, seizures can occur in about 0.4% patients and this effect has been proven to be related with immediate release tablets because of the peak in bupropion plasmatic concentration induced by such a dosage form. The development of a new sustained release dosage form has therefore been considered as an appropriate means to overcome this situation.... U.S. Pat. No. 5,358,970 and U.S. Pat. No. 5,427,798, both to Burroughs Wellcome, describe a sustained release formulation of bupropion hydrochloride based on matrix technology. The term matrix refers to a tablet where the drug is embedded in an excipient that makes a nondisintegrating core called matrix. Drug diffusion occurs through this core. As bupropion hydrochloride is unstable, the product described in the above two patents requires a stabilizer to achieve sufficient stability. This stabilizer is an acidic compound, preferably cysteine hydrochloride. Matrix technology is however not suited for the manufacture of a tablet, since it implies the use of a stabilizer.... U.S. Pat. No. 4,687,660 and EP-A0171457 disclose a tablet formed of a core and a coating, where the core comprises bupropion hydrochloride together with excipient(s) and optionally an osmotic enhancing agent and where the coating comprises a water-insoluble, water-permeable film-forming polymer (such as cellulose acetate), a pore-forming agent (such as impalpable lactose and sodium carbonate), and optionally a so-called waterpermeability enhancing agent (such as polyethyleneglycol) and again optionally a plasticizer. This type of coating, since it requires pore-forming agent, cannot provide a uniform coating and therefore the release rate cannot be uniform from one tablet to another. Web site: http://www.delphion.com/details?pn=US06143327__
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Delayed release tablet of bupropion hydrochloride Inventor(s): Seth; Pawan (Irvine, CA) Assignee(s): Pharma Pass LLC (Irvine, CA) Patent Number: 6,096,341 Date filed: October 30, 1998 Abstract: The invention provides a controlled release tablet, free of stabilizer and free of pore-forming agent comprising: (i) a core consisting essentially of bupropion
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hydrochloride, a binder and a lubricant; and (ii) a coating consisting essentially of a water-insoluble, water-permeable film-forming polymer, a plasticizer and a watersoluble polymer. Excerpt(s): Bupropion (its salt hydrochloride) is a widely used antidepressant drug. A commercial example is Wellbutrin.RTM.. This product consists in immediate release tablet, 75 or 100 mg strength. However it has been proven that bupropion hydrochloride can induce some severe side effects. For example, seizures can occur in about 0.4% patients and this effect has been proven to be related with immediate release tablets because of the peak in bupropion plasmatic concentration induced by such a dosage form. The development of a new sustained release dosage form has therefore been considered as an appropriate means to overcome this situation.... U.S. Pat. No. 5,358,970 and U.S. Pat. No. 5,427,798, both to Burroughs Wellcome, describe a sustained release formulation of bupropion hydrochloride based on matrix technology. The term matrix refers to a tablet where the drug is embedded in an excipient that makes a nondisintegrating core called matrix. Drug diffusion occurs through this core. As bupropion hydrochloride is unstable, the product described in the above two patents requires a stabilizer to achieve sufficient stability. This stabilizer is an acidic compound, preferably cysteine hydrochloride. Matrix technology is however not suited for the manufacture of a tablet, since it implies the use of a stabilizer.... U.S. Pat. No. 4,687,660 and EP-A0171457 disclose a tablet formed of a core and a coating, where the core comprises bupropion hydrochloride together with excipient(s) and optionally an osmotic enhancing agent and where the coating comprises a water-insoluble, water-permeable film-forming polymer (such as cellulose acetate), a pore-forming agent (such as impalpable lactose and sodium carbonate), and optionally a so-called waterpermeability enhancing agent (such as polyethyleneglycol) and again optionally a plasticizer. This type of coating, since it requires pore-forming agent, cannot provide a uniform coating and therefore the release rate cannot be uniform from one tablet to another. Web site: http://www.delphion.com/details?pn=US06096341__ •
Method for enhanced brain delivery of bupropion Inventor(s): Hussain; Anwar A. (Lexington, KY), Houdi; Abdulghani A. (Lexington, KY) Assignee(s): Theramax, Inc. (Lexington, KY) Patent Number: 6,150,420 Date filed: January 22, 1999 Abstract: This invention provides to a method for enhancement of delivery of bupropion by administration via the nasal route, and methods of treatment comprising intranasal administration of bupropion. The present invention further provides pharmaceutical compositions comprising bupropion and/or pharmaceutically acceptable salts thereof. Excerpt(s): This invention relates to a method for enhancement of delivery of bupropion by administration via the nasal route, and methods of treatment comprising intranasally administering an effective amount of bupropion to prevent or treat withdrawal symptoms associated with smoking nicotine to a patient in need of such prevention or treatment and for the treatment of depression.... Bupropion is well absorbed from the gastrointestinal tract after oral administration and is extensively metabolized in rat and man prior to excretion (9,10). Evidence suggests that bupropion has fewer autonomic
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and cardiovascular side effects than the tricyclic antidepressants (3-6). The three principal metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion appear to have slower clearance than bupropion, therefore they tend to accumulate to a greater extent than the parent drug during chronic bupropion therapy (10). It has been suggested that during chronic bupropion therapy, high hydroxybupropion concentrations may be associated with poorer clinical outcome (11,12). Furthermore, bupropion therapy is associated with seizures in approximately 0.4% of the patients treated with doses up to 450 mg/day. The incidence of seizures may exceed those of other antidepressants by up to fourfold, increasing to approximately tenfold at doses of 450-600 mg/day (7,8).... Combination therapy is often necessary in the treatment of mood disorders. Nevertheless, there are few data available regarding interactions between bupropion and other drugs. Clinical evidence suggests that the coadministration of fluoxetine (Prozac) and bupropion may yield delirium (13) and seizures (14) and that fluoxetine may increase hydroxybupropion and threohydrobupropion concentrations (15-18). Spontaneous postmarketing reports to the FDA are consistent with the possibility that fluoxetine inhibition of bupropion metabolism might yield seizures at lower bupropion dosages (19). Web site: http://www.delphion.com/details?pn=US06150420__ •
Method for treating depression using optically pure (-)-bupropion Inventor(s): Young; James W. (Palo Alto, CA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,369,113 Date filed: June 27, 2001 Abstract: Methods and compositions are disclosed utilizing the optically pure (-)-isomer of bupropion, which is a potent drug for treating depression. Excerpt(s): This invention relates to methods of treatment and pharmaceutical compositions employing the compound (-)-buproplon.... Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and 1 are employed to designate the sign of rotation of planepolarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.... Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the Lform of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06369113__
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Methods and compositions for aiding in smoking cessation and for treating pain and other disorders using optically pure (+)-bupropion Inventor(s): Rubin; Paul D. (Sudbury, MA), McCullough; John R. (Hudson, MA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 6,495,605 Date filed: March 13, 2001 Abstract: Methods and compositions are disclosed utilizing the optically pure (+)-isomer of bupropion to assist in smoking cessation, for treating smoking and nicotine addiction, and for treating pain, including, but not limited to, chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders such as narcolepsy, chronic fatigue syndrome, fibromyalgia, seasonal affective disorder and premenstrual syndrome, while avoiding adverse affects associated with racemic bupropion. Excerpt(s): This invention relates to methods and pharmaceutical compositions for aiding smoking cessation, treating nicotine addiction, and pain, including chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders.... Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and l are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.... Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06495605__
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Methods and compositions for treating chronic disorders using optically pure (+)bupropion Inventor(s): Rubin; Paul D. (Sudbury, MA), McCullough; John R. (Hudson, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,458,374 Date filed: January 28, 1999 Abstract: Methods and compositions are disclosed utilizing the optically pure (+)-isomer of bupropion to assist in smoking cessation, for treating smoking and nicotine addiction, and for treating pain, including, but not limited to, chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders such as narcolepsy, chronic fatigue syndrome, fibromyalgia, seasonal affective disorder and premenstrual syndrome, while avoiding adverse affects associated with racemic bupropion. Excerpt(s): This invention relates to methods and pharmaceutical compositions for aiding smoking cessation, treating nicotine addiction, and pain, including chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders.... Many
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organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and l are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.... Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06458374__ •
Methods and formulations for making bupropion hydrochloride tablets using direct compression Inventor(s): McGuffy; Kevin Scott (Stanhope, NJ), Kumar; Vijai (Morris Plains, NJ) Assignee(s): Pharmalogix, Inc. (Denville, NJ) Patent Number: 6,238,697 Date filed: December 21, 1998 Abstract: Methods and formulations for making extended release bupropion hydrochloride tablets using direct compression, and tablets formed thereby, are provided which combine bupropion hydrochloride, binders such as polyethylene oxide or hydroxypropyl cellulose, a filler such as lactose, glidants and lubricants under low shear conditions to form hard, chip-resistant tablets which exhibit improved cohesiveness and are easily and reproducibly formed without adhering to the compression punches and dies. Excerpt(s): Pharmaceutical manufacturers are continuously attempting to improve methods for delivering drugs to enhance and sustain their effects in human therapy. A significant development in drug delivery systems occurred in 1972 with the development of osmotic delivery systems as described by U.S. Pat. Nos. 3,845,770 and 3,916,899. Modifications to the rate-controlling osmotic delivery systems of the prior art are also disclosed in U.S. Pat. Nos. 4,816,263 and 4,902,514.... Such modified osmotic delivery systems use a semi-permeable wall to surround an interior containing the drug to be delivered. The external wall is permeable to the passage of an external fluid and may not be permeable to the drug. Such systems may include at least one outlet in the wall for delivering the drug through the osmotic system. The systems operate by absorbing gastric fluid through the semi-permeable wall into the interior of the dosage form at a rate determined by the permeability of the semi-permeable wall and the osmotic pressure gradient across the semi-permeable wall. The absorbed fluid produces an aqueous solution containing the drug that is then delivered to the body through at least one opening in the wall.... U.S. Pat. No. 4,816,263 discloses an osmotic device form for delivering isradipine to a biological receptor site in a rate-controlled amount over a prolonged period for cardiovascular therapy. The pharmaceutical dosage form adapted, designed, and shaped as an osmotic drug delivery system is manufactured by wet granulation and includes two compositions which form a bi-layered tablet coated by a semi-permeable wall. The first composition includes the drug and contains polyethylene
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oxide having a molecular weight of 200,000 which is screened through a 40 mesh screen. Specific amounts of isradipine and hydroxypropyl methylcellulose having a molecular weight of 11,200 are added to the polyethylene oxide and slowly mixed with denatured, anhydrous ethanol using a conventional mixer. The wet granulation formed is then passed through a 20 mesh screen, dried at room temperature and passed through the 20 mesh screen again. Magnesium stearate is then added to the granulation and mixed in a roller mill. Web site: http://www.delphion.com/details?pn=US06238697__ •
Methods for treating depression and other disorders using optically pure (-)bupropion Inventor(s): Young; James W. (Palo Alto, CA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,451,860 Date filed: February 19, 2002 Abstract: Methods are disclosed utilizing the optically pure (-)-isomer of bupropion, which is a potent drug for treating depression, Parkinson's disease, obesity, weight gain and other disorders. Excerpt(s): This invention relates to methods of treatment and pharmaceutical compositions employing the compound (-)-bupropion.... Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and l are employed to designate the sign of rotation of planepolarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.... Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the Lform of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06451860__
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Methods for treating obesity and weight gain using optically pure (-)-bupropion Inventor(s): Young; James W. (Palo Alto, CA) Assignee(s): Sepracor (Marlborough, MA) Patent Number: 6,110,973 Date filed: January 28, 1999 Abstract: Methods are disclosed utilizing the optically pure (-)-isomer of bupropion, which is a potent drug for treating obesity and weight gain.
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Excerpt(s): This invention relates to methods of treatment and pharmaceutical compositions employing the compound (-)-bupropion.... Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and l are employed to designate the sign of rotation of planepolarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.... Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the Lform of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06110973__ •
Methods for treating Parkinson's disease using optically pure (-)-bupropion Inventor(s): Young; James W. (Palo Alto, CA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,277,887 Date filed: April 20, 2000 Abstract: Methods and compositions are disclosed utilizing the optically pure (-)-isomer of bupropion, which is a potent drug for treating, Parkinson's disease. Excerpt(s): This invention relates to methods of treatment and pharmaceutical compositions employing the compound (-)-bupropion.... Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and 1 are employed to designate the sign of rotation of planepolarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.... Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the Lform of the.beta. -adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06277887__
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Patch and method for transdermal delivery of bupropion base Inventor(s): Hirsh; Mark (Wellesley, MA), Midha; Kamal K. (Hamilton, BM), Junginger; Hans E. (Wellesley, MA) Assignee(s): Peierce Management LLC (Wellesley, MA) Patent Number: 6,312,716 Date filed: May 2, 2000 Abstract: The invention includes a patch and method for transdermal delivery of bupropion base. In the method of this invention, a patient is administered a bupropion base in an amount effective to alleviate withdrawal symptoms and to prevent or reduce craving of nicotine in said patient. Alternatively, an effective amount of bupropion base is delivered to alleviate depression in a patient or to treat obesity. A transdermal patch includes a bupropion base. The bupropion base can be mixed with an acceptable pharmaceutical carrier. Excerpt(s): This application relates to a method of transdermally administering bupropion base to a mammal to treat depression and to alleviate withdrawal symptoms from tobacco smoking thereby enhancing the ability of a patient to abstain from smoking. More particularly the invention relates to a patch containing stabilized bupropion base enabling successful transdermal administration of bupropion base to a patient.... Bupropion hydrochloride is a known antidepressant sold in immediate release and sustained release tablet form under the brand names WELLBUTRIN.RTM. and ZYBAN.RTM.. Bupropion hydrochloride is an antidepressant of the aminoketone class and is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitors or other known antidepressant agents. Bupropion (BUP) hydrochloride is highly metabolized in both rats and humans. The major metabolites are the erythroamino alcohol (EB), the threoamino alcohol (TB), and the hydroxy metabolite (HB). The metabolites exhibit pharmacological activity in an antitetrabenzene model. Bupropion hydrochloride is also used in preventing functional impairment and drowsiness seen upon administration of benzodiazepine, in the treatment of minimal brain dysfunction, tardive dyskinesia, impaired mental alertness upon ingestion of ethanol and psychosexual dysfunction and in promoting weight loss. While the immediate release and sustained release tablets currently sold are suitable for the indicated use, there is a disadvantage to bupropion hydrochloride in that there can be an accumulation of metabolites that can be detrimental to one's health.... In a study of pharmacokinetics of bupropion hydrochloride in the elderly, six elderly patients with diagnosed depression were examined in a single and multiple dose study. Half-lives (t1/2app) of the metabolites TB, EB and HB were 38.8+/-7.6 hours, 61.4 +/-21.6 hours and 34.2 +/-4.6 hours, respectively. After multiple dosing, the half-life for bupropion and its metabolites did not change significantly although in some patients the half-life of metabolites was substantially prolonged. In addition, there was also evidence of inordinate accumulation of metabolites. The elderly are at risk for accumulation of bupropion and its metabolites. See J. Clin. Pharmacol. 35:876-884 (1995). Web site: http://www.delphion.com/details?pn=US06312716__
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Pharmaceutical composition comprising bupropion hydrochloride and fumaric acid Inventor(s): Sherman; Bernarad Charles (50 Old Colony Road, Willowdale, Ontario, CA) Assignee(s): none reported Patent Number: 6,194,002 Date filed: August 5, 1999 Abstract: A pharmaceutical composition in solid dosage form comprising bupropion hydrochloride as active drug and fumaric acid as stabilizer. Excerpt(s): Bupropion hydrochloride is a well-known antidepressant. It is sold in the United States by Glaxo Wellcome Inc. as prompt release tablets under the tradename WELLBUTRIN.RTM. and sustained release tablets under the tradename, WELLBUTRIN SR.RTM..... Bupropion hydrochloride is known to be relatively unstable, such that tablets containing bupropion hydrochloride will degrade at an unacceptably high rate unless the tablets are made by a method or using ingredients which result in improved stability.... U.S. Pat. No. 5,358,970 discloses stabilization of bupropion hydrochloride by including in the tablets a stabilizer. The specific stabilizers disclosed are L-cysteine hydrochloride, glycine hydrochloride, ascorbic acid, malic acid, sodium metabisulfite, isoascorbic acid, citric acid, and L-cysteine hydrochloride. L-cysteine hydrochloride and glycerin hydrochloride are said to be most preferred. All of the examples in U.S. Pat. No. 5,358,970 use L-cysteine hydrochloride or glycine hydrochloride as the stabilizer, and, in each example, the process of manufacture includes the steps of dissolving the stabilizer in water and alcohol, using the solution to granulate the bupropion hydrochloride and other ingredients, and then drying the wet mass. Web site: http://www.delphion.com/details?pn=US06194002__
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Pharmaceutical composition containing bupropion hydrochloride and a stabilizer Inventor(s): Maitra; Amitava (Sayreville, NJ), DeVito; Joseph Michael (Middletown, NY), Shah; Bharat Bhogilal (Ridgefield, NJ), Kulkarni; Prakash Shriram (Parsippany, NJ) Assignee(s): Clonmel Healthcare, Ltd. (Tipperary, IE) Patent Number: 6,482,987 Date filed: April 2, 2001 Abstract: Novel, stable formulations of bupropion hydrochloride are provided which will maintain at least 80% of initial bupropion hydrochloride potency after one year. Methods of inhibiting degradation of bupropion hydrochloride and methods of preparing stable formulations of bupropion hydrochloride are also provided. Excerpt(s): Bupropion hydrochloride is a common antidepressant sold in immediate release, modified release, and extended release tablet forms. See U.S. Pat. Nos. 3,819,706 and 3,885,046. As with many pharmaceuticals, the stability of bupropion hydrochloride is affected by a number of factors including formulation microenvironments and storage conditions.... One formulation of bupropion hydrochloride is taught by Ruff et al., U.S. Pat. No. 5,358,970 to prevent or inhibit degradation of bupropion hydrochloride using one of the stabilizers L-cysteine hydrochloride, glycine hydrochloride, malic acid, sodium metabisulfite, citric acid, tartaric acid and L-cystine dihydrochloride. These solid dosage forms were prepared using alcohol granulation technology. However, granulation technology is labor intensive and costly. In addition special procedures are necessary to address safety and environment issues involving the use of alcohol....
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Accordingly, stable bupropion hydrochloride formulations prepared by safe, cost effective methods are greatly desired. The present invention provides such stable bupropion hydrochloride formulations. Web site: http://www.delphion.com/details?pn=US06482987__ •
Stabilized pharmaceutical composition containing bupropion Inventor(s): Kalidindi; Sanyasi Raju (Edison, NJ), Sutton, Jr. Joel Elmore (Greenville, NC), Ruff; Michael David (Greenville, NC) Assignee(s): Glaxo Wellcome Inc. (Rtp, NC) Patent Number: 5,731,000 Date filed: March 22, 1996 Abstract: This application discloses a method of inhibiting degradation of the antidepressant bupropion hydrochloride in a solid pharmaceutical formulation, so that the pharmaceutical formulation will maintain at least 80% of its initial bupropion potency after one year. Excerpt(s): The present invention relates to pharmaceutical compositions comprising bupropion hydrochloride and a pharmaceutically acceptable stabiliser and methods of stabilising bupropion hydrochloride in a pharmaceutical composition.... Bupropion hydrochloride is a known antidepressant sold in instant release tablet form under the brand name WELLBUTKIN.RTM.. (Also see U.S. Pat. Nos. 3,819,706 and 3,885,046; 1993 Physicians Desk Reference and the Merck Index, Eleventh Edition, Entry No. 1488. Bupropion hydrochloride is also useful as an anticholesterol agent, in suppressing prolactin secretion, in preventing functional impairment and drowsiness seen upon administration of benzodiazepine, in the treatment of minimal brain dysfunction, tardive dyskinesia, impaired mental alertness upon ingestion of ethanol and psychosexual dysfunction. While the instant release tablets currently sold are quite suitable for the indicated use, the method of manufacturing these is less than desirable based on cost as well as process conditions.... The object of the present invention is to prevent (inhibit) the degradation of bupropion hydrochloride, using stabiliser ingredients, thus allowing the preparation of pharmaceutical compositions such as instant and sustained release tablets and capsules which, from a cost of manufacture and processing standpoint, are much improved over those achievable in the past. Web site: http://www.delphion.com/details?pn=US05731000__
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Stabilized pharmaceutical compositions containing bupropion hydrochloride Inventor(s): Liaw; Gary (Torrance, CA), Han; Chien-Hsuan (Sunnyvale, CA) Assignee(s): Impax Laboratories, Inc. (Hayward, CA) Patent Number: 6,333,332 Date filed: August 25, 2000 Abstract: This invention is directed to stabilized pharmaceutical preparations containing bupropion hydrochloride. The preferred stabilizers comprise salts of organic bases including those selected from the group consisting of creatinine hydrochloride, pyridoxine hydrochloride, and thiamine hydrochloride. Another stabilizer utilized includes a salt of an inorganic acid such as potassium phosphate monobasic. The
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compositions retain at least 80% of the initial potency of bupropion hydrochloride after one week at 60.degree. and 75% relative humidity (RH), as well as four or twelve weeks at 40.degree. C. and 75% RH. Excerpt(s): This invention is directed to stabilized pharmaceutical preparations containing bupropion hydrochloride.... Bupropion hydrochloride is a common chloropropiophenone antidepressant, most recently found useful for helping patients stop smoking. See PCT Application No. WO 99/38,499. Novel methods of making bupropion hydrochloride include those taught by Mehta. See U.S. Pat. Nos. 3,819,706 and 3,885,046. Relative to conventional antidepressants, bupropion hydrochloride has no significant sympathomimetic, sympatholytic, anticholinergic or cardiovascular effects. Bupropion hydrochloride is sold in immediate release, modified release and extended release tablet forms. Regardless of its form, stability of bupropion hydrochloride is affected by a number of factors including formulation microenvironments and storage conditions.... Various bupropion hydrochloride formulations have been proposed in the art, designed to increase its stability. For example, one group reports that degradation can be inhibited or prevented by including in the formulation stabilizers such as L-cysteine hydrochloride, glycine hydrochloride, malic acid, sodium metabisulfite, citric acid, tartaric acid and L-cystine dihydrochloride. See U.S. Pat. Nos. 5,358,970 and 5,763,493. The same group also reports that degradation of bupropion hydrochloride can be inhibited by use of stabilizers including ascorbic acid or isoascorbic acid. See U.S. Pat. Nos. 5,541,231 and 5,731,000. Another group has reported that the drug can be stabilized by formulating it with inorganic acids such as hydrochloric acid, phosphoric acid, nitric acid and sulfuric acid or combinations thereof. See U.S. Pat. No. 5,968,553 and PCT Application No. WO 99/33,456. Still others have reported that substances such as fumaric acid can inhibit degradation of bupropion hydrochloride. See PCT Application No. WO 99/33,457. Web site: http://www.delphion.com/details?pn=US06333332__ •
Stabilized, acid-free formulation for sustained release of bupropion hydrochloride Inventor(s): Lin; Kangwen (Sharon, MA), Chungi; Shubha (Sharon, MA) Assignee(s): Teva Pharmaceuticals USA, Inc. (North Wales, PA) Patent Number: 6,306,436 Date filed: April 28, 2000 Abstract: Stabilized bupropion hydrochloride pharmaceutical compositions are disclosed that are free of acid additives and provide for a sustained release of the bupropion hydrochloride. The particulate bupropion hydrochloride may be coated with a membrane coating and large-size particles may also be used. Methods for treating individuals using the stabilized bupropion hydrochloride pharmaceutical compositions are also provided. Excerpt(s): The present invention relates generally to sustained release bupropion hydrochloride compositions, and more specifically relates to such compositions in which the drug is stabilized without added acid. The invention additionally relates to methods for administering bupropion using the novel formulations. The invention finds utility in the fields of drug delivery, pharmacology and medicine.... and is used as both an antidepressant and a smoking cessation aid. Utility in treating attention deficit hyperactivity disorder (ADHD) has also been evaluated. Bupropion hydrochloride is a water-soluble, crystalline solid having a melting point of 233-234.degree. C., and is
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highly hygroscopic and susceptible to decomposition. Because of the drug's instability, the shelf-life of bupropion formulations has proved to be problematic, and those working in the field have tried a number of different approaches to improving the storage stability of the drug.... For example, U.S. Pat. Nos. 5,541,231, 5,763,493, 5,358,970, and 5,731,000 to Ruff et al. describe bupropion hydrochloride formulations that use an organic acid, a carboxylic acid, an amino acid salt (e.g., cysteine hydrochloride, glycine hydrochloride, and cysteine dihydrochloride), or sodium metabisulfite as a stabilizer. PCT Publication No. WO 99/33457 to Kulkani et al. describes bupropion hydrochloride formulations containing dicarboxylic acids as stabilizing agents. U.S. Pat. No. 5,968,553 to Maitra et al. describes bupropion hydrochloride formulations containing dilute inorganic acids as stabilizers including hydrochloric acid, phosphoric acid, nitric acid, and sulfuric acid. Acid stabilization of the related compound diethylpropion hydrochloride has also been described by Walters (1980) J. Pharm. Sci. 69(10):1206-1209. Placing bupropion HCl in a relatively low pH environment has proven effective in stabilizing bupropion and its major metabolites in human plasma; see Laizure et al. (1985) Ther. Drug Monit. 7(4): 447-450. Unfortunately, the use of acidic materials in pharmaceutical formulations requires costly production procedures and equipment. Therefore, it would be desirable to produce a stabilized bupropion hydrochloride formulation without the use of acid stabilizers. Web site: http://www.delphion.com/details?pn=US06306436__
Patent Applications on Bupropion 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 bupropion: •
Bupropion metabolites and methods of their synthesis and use Inventor(s): Grover, Paul; (Franklin, MA), Senanayake, Chrisantha Hugh; (Shrewsbury, MA), Fang, Kevin Qun; (Wellesley, MA) Correspondence: PENNIE & EDMONDS LLP; 1667 K STREET NW; SUITE 1000; WASHINGTON; DC; 20006 Patent Application Number: 20020052341 Date filed: November 16, 2001 Abstract: Methods and compositions are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, but are not limited to, sexual dysfunction, affective disorders, cerebral function disorders, cigarette smoking, and incontinence. Methods of making optically pure bupropion metabolites are also disclosed. Excerpt(s): This application is a continuation-in-part of copending application No. 09/510,241, filed Feb. 22, 2000, which claims priority to provisional application No. 60/148,324, filed Aug. 11, 1999, and provisional application No. 60/122,277, filed Mar. 1, 1999, each of which is incorporated herein by reference.... This invention relates to the synthesis of, methods of using, and compositions comprising bupropion metabolites,
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This has been a common practice outside the United States prior to December 2000.
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their isomers, and salts thereof.... Bupropion, a racemic mixture of (+)- and (-)-1-(3chlorophenyl)-2-[- (1,1-dimethylethyl)amino]-1-propanone, is an antidepressant of the aminoketone class, which is described in U.S. Pat. Nos. 3,819,706 and 3,885,046. The hydrochloride salt of bupropion is sold under the tradenames WELLBUTRIN.RTM. and WELLBUTRIN SR.RTM. (Glaxo Wellcome Inc.) for the treatment of depression. Bupropion is also sold under the tradename ZYBAN.RTM. (Glaxo Wellcome Inc.) as a drug useful to achieve smoking cessation. Additional benefits of bupropion maleate are reported in European Patent Application No. 118036. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Bupropion to treat viral diseases Inventor(s): Reindler, Christopher William; (Como, AU) Correspondence: KENYON & KENYON; 1500 K STREET, N.W., SUITE 700; WASHINGTON; DC; 20005; US Patent Application Number: 20030134905 Date filed: July 1, 2002 Abstract: Disclosed is a method and composition for the treatment and prevention of a viral infection in a human or animal subject by administering bupropion or a physiologically acceptable salt, solvate or enantiomer thereof. Preferably, the virus is a virus of the Herpes family or condition caused thereby, particularly HSV1 or HSV2. Excerpt(s): This invention relates to a new medical use for bupropion and physiologically acceptable salts and solvates thereof. Specifically the invention concerns the use of bupropion in treating viral infections, more particularly infections caused by viruses of the Herpes family.... Bupropion hydrochloride, (.+-.)-1-(3-chlorophenyl)-2[(1,1-dimethyl- ethyl)-amino)-1-propanone hydrochloride has been used for the treatment of depression. Bupropion is a relatively weak inhibitor of the neuronal uptake of noradrenahne (NA), serotonin and dopamine (DA), and does not inhibit monoamine oxidase. While the mechanism of action of bupropion, as with other antidepressants, is unknown, it is presumed that this action is mediated by noradrenergic and/or doparninergic mechanisms. Available evidence suggests that bupropion is a selective inhibitor of noradrenaline (NA) at doses that are predictive of antidepressant activity in animal models. See Ascher, J. A., et al., Bupropion: A Review of its Mechanism of Antidepressant Activity. Journal of Clinical Psychiatry, 56: p. 395-401,1995.... It has also been disclosed that bupropion is useful for the treatment of migraine (U.S. Pat. No. 5,753,712), reducing cholesterol (U.S. Pat. No. 4,438,138), treatment of minimal brain dysfunction (U.S. Pat. No. 4,435,449), treatment of tardive dyskinesia (U.S. Pat. No. 4,425,363), reversing impaired mental alertness due to ethanol consumption (U.S. Pat. No. 4,393,078), treatment of psychosexual dysfunction (U.S. Pat. No. 4,507,323), suppressing prolactin secretion (U.S. Pat. No. 4,347,257) and as an aid to smoking cessation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions for aiding in smoking cessation and for treating pain and other disorders using optically pure (+)-bupropion Inventor(s): Rubin, Paul D. (Sudbury, MA), McCullough, John R. (Hudson, MA) Correspondence: PENNIE & EDMONDS LLP; 1667 K STREET NW; SUITE 1000; WASHINGTON; DC; 20006 Patent Application Number: 20030096873 Date filed: October 23, 2002 Abstract: Methods and compositions are disclosed utilizing the optically pure (+)-isomer of bupropion to assist in smoking cessation, for treating smoking and nicotine addiction, and for treating pain, including, but not limited to, chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders such as narcolepsy, chronic fatigue syndrome, fibromyalgia, seasonal affective disorder and premenstrual syndrome, while avoiding adverse affects associated with racemic bupropion. Excerpt(s): This invention relates to methods and pharmaceutical compositions for aiding smoking cessation, treating nicotine addiction, and pain, including chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders.... Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and 1 are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.... Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.energic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions for treating depression and other disorders using optically pure (-)-bupropion Inventor(s): Young, James W. (Palo Alto, CA) Correspondence: PENNIE & EDMONDS LLP; 1667 K STREET NW; SUITE 1000; WASHINGTON; DC; 20006 Patent Application Number: 20030022942 Date filed: July 26, 2002 Abstract: Methods and compositions are disclosed utilizing the optically pure (-)-isomer of bupropion, which is a potent drug for treating depression, Parkinson's disease, obesity, weight gain and other disorders. Excerpt(s): This invention relates to methods of treatment and pharmaceutical compositions employing the compound (-)-bupropion.... Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are
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used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and l are employed to designate the sign of rotation of planepolarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture.... Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the Lform of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Modified release pharmaceutical composition containing bupropion HCI as active substance Inventor(s): Avanessian, Serozh; (Rimini, IT), Valducci, Roberto; (Savignano sul Rubicone, IT), Alighieri, Tiziano; (Rimini, IT) Correspondence: William J. Sapone; 714 Colorado Avenue; Bridgeport; CT; 06605; US Patent Application Number: 20030134906 Date filed: May 31, 2002 Abstract: Pharmaceutical composition in modified release tablet form containing Bupropion HCl as active substance and including, at the same time, hydrophilic components and hydrophobic ingredients mixed with an excipient substance. Excerpt(s): Bupropion HCl is a substance having interesting pharmacological characteristics, similar to those of the tricyclic antidepressants.... Nevertheless Bupropion HCl has an elevated hygroscopicity and susceptibility to the decomposition.... For this reason various compositions with stabilizing intent have been studied. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Pharmaceutical composition containing bupropion hydrochloride and a stabilizer Inventor(s): DeVito, Joseph Michael; (Middletown, NY), Maitra, Amitava; (Sayreville, NJ), Kulkarni, Prakash Shriram; (Parsippany, NJ), Shah, Bharat Bhogilal; (Ridgefield, NJ) Correspondence: BARRETT, REBECCA RALPH; WYETH AYERST; P.O BOX 8299; PHILADELPHIA; PA; 19101; US Patent Application Number: 20010021721 Date filed: April 2, 2001 Abstract: Novel, stable formulations of bupropion hydrochloride are provided which will maintain at least 80% of initial bupropion hydrochloride potency after one year. Methods of inhibiting degradation of bupropion hydrochloride and methods of preparing stable formulations of bupropion hydrochloride are also provided. Excerpt(s): Bupropion hydrochloride is a common antidepressant sold in immediate release, modified release, and extended release tablet forms. See U.S. Pat. Nos. 3,819,706
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and 3,885,046. As with many pharmaceuticals, the stability of bupropion hydrochloride is affected by a number of factors including formulation microenvironments and storage conditions.... One formulation of bupropion hydrochloride is taught by Ruff et al., U.S. Pat. No. 5,358,970 to prevent or inhibit degradation of bupropion hydrochloride using one of the stabilizers L-cysteine hydrochloride, glycine hydrochloride, malic acid, sodium metabisulfite, citric acid, tartaric acid and L-cystine dihydrochloride. These solid dosage forms were prepared using alcohol granulation technology. However, granulation technology is labor intensive and costly. In addition special procedures are necessary to address safety and environment issues involving the use of alcohol.... Accordingly, stable bupropion hydrochloride formulations prepared by safe, cost effective methods are greatly desired. The present invention provides such stable bupropion hydrochloride formulations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Sustained release tablets containing bupropion hydrochloride Inventor(s): Shanmugam, Muthusamy; (Edison, NJ), Subramanian, Veerappa S. (Edison, NJ) Correspondence: Kent H. Cheng, Esq. Cohen, Pontani, Lieberman & Pavane; Suite1210; 551 Fifth Avenue; New York; NY; 10176; US Patent Application Number: 20030044462 Date filed: August 20, 2001 Abstract: This application describes a method of preparing stabilized sustained release tablets containing bupropion hydrochloride and carboxyvinyl polymers, in which the composition contains, at least about 90% w/w of undegraded Bupropion hydrochloride after storage for two weeks at 55.degree. C. and for three months at 40.degree. C. and 75% relative humidity. Excerpt(s): Bupropion hydrochloride is a known antidepressant, which is marketed as a sustained release tablet form under the brand name of Wellbutrin.RTM. by Glaxo Wellcome, Inc. It is chemically known as 1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride (see U.S. Pat. Nos. 3,819,706 and 3,885,046, and Merck Index, Eleventh Edition, entry no. 1488). Bupropion hydrochloride is a stability prone product when formulated with conventional pharmaceutical excipients into solid dosage form. Though exact mechanism of degradation has not been fully elucidated, literature and patent information seem to indicate that hydrolysis and oxidation are the possible mechanisms of degradation. The main degradation product is 3-chlorobenzoic acid.... U.S. Pat. Nos. 5,541,231; 5,358,970 and 5,731,000 disclose that ascorbic acid, isoascorbic acid, L-Cysteine hydrochloride, glycine hydrochloride, malic acid, citric acid, fumaric acid, sodium metabisulfite, and L-Cysteine dihydrochloride inhibit the degradation of bupropion hydrochloride in pharmaceutical preparations. U.S. Pat. No. 5,968,553 discloses a novel tablet formulation comprising bupropion hydrochloride and inorganic acid stabilizers selected from the group consisting of hydrochloric acid, phosphoric acid, nitric acid and sulfuric acid. U.S. Pat. No. 5,427,798 discloses sustained release tablets containing bupropion hydrochloride with use of cellulose polymer (hydroxy propylmethyl cellulose), which provides an improved product as well as ease of manufacture over prior U.S. Pat. No. 4,687,660.... Currently, marketed immediate release tablets, for example, the 75 mg and 100 mg, when administered to humans for treatment of depression, are given one to three times per day in order to provide a total daily dosage of 150 mg to 450 mg for the duration of treatment as determined by the
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physician. The present invention would reduce the frequency of dosing, and thus enhance compliance of dosage regimen, since it would provide for a possible one or two times a day administration, rather than the three times per day. Modified release and extended release dosage forms are encompassed by the present invention. 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 bupropion, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “bupropion” (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 bupropion. You can also use this procedure to view pending patent applications concerning bupropion. Simply go back to the following Web address: 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 7. BOOKS ON BUPROPION Overview This chapter provides bibliographic book references relating to bupropion. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bupropion include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Chapters on Bupropion In order to find chapters that specifically relate to bupropion, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and bupropion 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 “bupropion” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on bupropion: •
Recommending Specific Pharmacotherapy for Specific Patient Subgroups Source: in Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD, U.S. Department of Health and Human Services, Public Health Service, pp. 80-90, June 2000. Contact: U.S. Department of Health and Human Services, Public Health Service. Summary: Recommending Specific Pharmacotherapy for Specific Patient Subgroups, a chapter in Treating Tobacco Use and Dependence: Clinical Practice Guideline, provides patient selection guidelines for the use of the five Food and Drug Administrationapproved medications for treating tobacco dependence: (1) bupropion SR, (2) nicotine gum, (3) nicotine inhaler, (4) nicotine nasal spray, and (5) nicotine patch. The guidelines cover precautions in pregnancy and for patients with cardiovascular diseases, dependency, side effects, contraindications, dosage, availability, prescribing instructions and cost per day. Two second-line pharmacotherapies were identified as efficacious and
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may be considered by clinicians if first-line pharmacotherapies are not effective: (1) Clonidine and (2) nortriptyline.
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CHAPTER 8. PERIODICALS AND NEWS ON BUPROPION Overview In this chapter, we suggest a number of news sources and present various periodicals that cover bupropion.
News Services and Press Releases One of the simplest ways of tracking press releases on bupropion 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 “bupropion” (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 bupropion. 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 “bupropion” (or synonyms). The following was recently listed in this archive for bupropion: •
U.S. approves Glaxo once-daily antidepressant, Wellbutrin XL Source: Reuters Medical News Date: August 29, 2003 http://www.reutershealth.com/archive/2003/08/29/professional/links/20030829rglt0 02.html
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GSK prepares aggressive Levitra, Wellbutrin XL promotion in United States Source: Reuters Industry Breifing Date: July 23, 2003
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Bupropion fails to delay relapse to smoking Source: Reuters Industry Breifing Date: April 04, 2003
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Biovail, Glaxo ink new deal on Wellbutrin Source: Reuters Industry Breifing Date: December 27, 2002
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Glaxo files for US approval of once-daily Wellbutrin Source: Reuters Industry Breifing Date: August 27, 2002
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Bupropion SR effective for smoking cessation in African Americans Source: Reuters Industry Breifing Date: July 23, 2002
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GlaxoSmithKline gets FDA approval for higher Wellbutrin SR dose Source: Reuters Industry Breifing Date: June 18, 2002
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Norwegian authorities disallow Glaxo Zyban marketing plan Source: Reuters Industry Breifing Date: May 30, 2002
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Court rules Andrx's generic Wellbutrin SR, Zyban do not infringe Glaxo patents Source: Reuters Industry Breifing Date: March 01, 2002
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EMEA review of Zyban prompted by reports of adverse effects Source: Reuters Medical News Date: February 22, 2002
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Zyban use associated with 57 deaths in UK, but link unclear Source: Reuters Medical News Date: January 17, 2002
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Deaths among Zyban users in UK reaches 57 Source: Reuters Industry Breifing Date: January 17, 2002
Periodicals and News
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Bupropion SR treats neuropathic pain Source: Reuters Industry Breifing Date: November 12, 2001
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Biovail strikes deal for Wellbutrin, Zovirax with Glaxo Source: Reuters Industry Breifing Date: October 29, 2001
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Long-term bupropion delays relapse after smoking cessation, lessens weight gain Source: Reuters Industry Breifing Date: September 17, 2001
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Bupropion promotes weight loss in overweight women Source: Reuters Industry Breifing Date: September 17, 2001
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German doctors assert Zyban link to deaths Source: Reuters Industry Breifing Date: September 13, 2001
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Retreatment with bupropion SR is effective for smoking cessation Source: Reuters Medical News Date: August 01, 2001
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Bupropion use associated with erythema multiforme Source: Reuters Industry Breifing Date: July 03, 2001
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Bupropion found effective for bereavement Source: Reuters Industry Breifing Date: June 04, 2001
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UK issues tougher warnings on Zyban Source: Reuters Medical News Date: May 31, 2001
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UK issues tougher warnings on Glaxo's Zyban Source: Reuters Industry Breifing Date: May 31, 2001
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Zyban most effective for males, older smokers Source: Reuters Health eLine Date: May 28, 2001
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Zyban helps smokers with lung disease quit: study Source: Reuters Health eLine Date: May 21, 2001
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Bupropion SR may help patients with COPD stop smoking Source: Reuters Industry Breifing Date: May 18, 2001
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Bupropion may treat hypoactive sexual desire disorder in women Source: Reuters Medical News Date: April 19, 2001
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Retreatment with bupropion is successful for some relapsed smokers Source: Reuters Industry Breifing Date: March 26, 2001
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Glaxo says no evidence of Zyban stroke link Source: Reuters Industry Breifing Date: November 17, 2000
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Drug company says no evidence of Zyban stroke link Source: Reuters Health eLine Date: November 17, 2000
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Drug company denies link between Zyban use, stroke Source: Reuters Medical News Date: November 17, 2000
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Eon receives FDA approval of generic formulation of Wellbutrin Source: Reuters Industry Breifing Date: October 11, 2000
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Glaxo files patent suit against Impax for Wellbutrin, Zyban ANDAs Source: Reuters Industry Breifing Date: October 10, 2000
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Use of bupropion for smoking cessation linked to less weight gain than placebo Source: Reuters Industry Breifing Date: August 09, 2000
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UK decision to reimburse Zyban angers nicotine replacement makers Source: Reuters Industry Breifing Date: June 28, 2000
Periodicals and News
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FDA approves Mylan's generic bupropion tablet Source: Reuters Industry Breifing Date: April 20, 2000
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FDA approves Teva's bupropion tablets Source: Reuters Medical News Date: December 01, 1999
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Smoking cessation higher with bupropion than with nicotine patch Source: Reuters Medical News Date: March 04, 1999
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Sustained-Release Bupropion Safe And Effective For Smoking Cessation Source: Reuters Medical News Date: October 23, 1997
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Efficacy Of Bupropion Equal To Methylphenidate For Treatment Of AttentionDeficit Hyperactivity Disorder Source: Reuters Medical News Date: April 21, 1995
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “bupropion” (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.
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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 “bupropion” (or synonyms). If you know the name of a company that is relevant to bupropion, 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 “bupropion” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “bupropion” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on bupropion: •
Secrets of Successful Quitters Source: Diabetes Advisor. 7(5): 20-21. September-October 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article provides people who have diabetes with guidelines for quitting smoking. The article identifies the physical symptoms associated with quitting and explains that successful quitters go through several rounds of quitting and resuming smoking before they quit for good. The article presents initial steps that a person who wants to quit smoking needs to take and discusses the use of various nicotine replacement products to make withdrawal easier. Types of nicotine replacement products include the nicotine patch, nicotine gum, and nicotine nasal spray. In addition, the drug bupropion has been used as a smoking cessation aid since 1997. Other approaches to quitting include receiving formal training in the skills of quitting and undergoing acupuncture or hypnosis. The article also provides suggestions for reducing smoking as a way of easing into quitting and offers tips for making quitting easier, finding a smoking cessation program, and reducing postcessation weight gain.
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Academic Periodicals covering Bupropion Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to bupropion. In addition to these sources, you can search for articles covering bupropion 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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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
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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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
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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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
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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
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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/
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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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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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/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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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
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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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
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “bupropion” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “bupropion” (or synonyms) into the “For these words:” box. The following is a sample result: •
Tobacco Control in Arizona Healthcare Systems Survey 2000 Source: Phoenix, AZ, Tobacco Education and Prevention Program, 67 p., 2001. Contact: Tobacco Education and Prevention Program, 1740 West Adams, no. 203-S, Phoenix, AZ 85007-2670. (602) 364-0824. FAX: (602) 364-0844. INTERNET/EMAIL: http://www.tepp.org/actev/healthcare/ healthcare_systems_survey_2000.pdf. Summary: Tobacco Control in Arizona Healthcare Systems Survey 2000 provides the results of a survey conducted by the Arizona Department of Health Services Tobacco Education and Prevention Program and the Arizona Healthcare Partnership. These two groups designed this survey of 40 health care systems in Arizona to assess the availability of tobacco cessation and prevention services for their members. These systems included 9 commercial managed care organizations (MCO's), 8 Medicare MCO's, 12 Arizona Health Care Cost Containment System MCO's, 3 Veterans Affairs Healthcare Systems, and 8 Indian Health Service Medical Centers. Of the 33 respondents, 11 enrolled less than 25,000 members, 15 enrolled between 25,000 and 250,000 members, and 7 had more than 250,000 members. Results showed that (1) 29 systems (88 percent) indicated awareness of tobacco cessation and prevention guidelines, (2) 18 (55 percent) indicated that there was full or partial implementation of at least one tobacco cessation and prevention practice guideline, (3) 23 (70 percent) were aware of or referred to the Arizona Smokers' Helpline for services, and (4) 22 (67 percent) were aware of or referred to the Arizona Department of Health Services Tobacco Education and Prevention Program Local Projects for tobacco cessation services. Other results showed that (1) all health care systems reported the existence of tobacco-free workplace policies for employees, (2) 12 (36 percent) stated that protocols/policies were in place for enrollees, (3) the most frequently reported protocols or policies were documentation of tobacco use in the medical record and measurement of tobacco use by enrollees, (4) 23 (70 percent) reported full coverage for at least one form of counseling, and (5) 14 (42 percent) reported that nicotine replacement therapy and bupropion were fully or partially covered. Barriers to tobacco control included (1) lack of requests from health plan purchasers, (2) insufficient staff, and (3) cost of implementing guidelines.
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•
Smoke-free Families Phase Two Research Projects Source: Smoke-free Families, 17 p., (n.d.). Contact: Smoke-free Families National Dissemination Office, Cecil G. Sheps Center for Health Services Research, CB 7590, 725 Airport Road, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7590. (919) 843-7663. INTERNET/EMAIL: http://www.smokefreefamilies.org/roundtwo.html;
[email protected]. Summary: Smoke-free Families Phase Two Research Projects summarizes research projects sponsored by Smoke-free Families. Smoke-free Families provides grants to a variety of institutions and organizations to develop interventions to help women stop smoking during and beyond pregnancy. Phase Two research projects currently in progress include (1) Smoking Cessation in Mothers and Other Household Members of Babies Being Treated in a Special Care Nursery; (2) Determinants and Trajectories of Smoking Cessation, Maintenance, and Relapse Among Pregnant and Postpartum Adolescents: A Naturalistic Qualitative Study; (3) STOPP (Sustained Treatments over the Perinatal Period); (4) Maternal Interventions to Stop Smoking (MISS); (5) Smoke Free Connections: Helping Pregnant Women Build Support for Not Smoking; (6) Efficacy of Ultrasound and Motivational Enhancement for Prenatal Smoking Cessation; (7) Role for Visiting Nurses in Preventing Postpartum Relapse; (8) Mapping the Natural History of Smoking and Smoking Cessation among Pregnant Women; (9) Motivational Intervention for Pregnant Women Who Continue to Smoke after Receipt of Best Practice Cessation Services; (10) Telephone Counseling Program for Pregnant Smokers; (11) Randomized Controlled Trial of Sustained Release bupropion for Prevention of Relapse in Women who Quit Smoking during Pregnancy; (12) Development and Formative Evaluation of Motivational Enhancements for a Stage-based Expert-system Driven Smoking Cessation Intervention for Low Income Pregnant Women; (13) Personal Meaning of Smoking; (14) Motivational Counseling and Immediate Biofeedback (Dipstick); and (15) Perinatal Depressive Symptoms and Smoking.
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 “bupropion” (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.
14 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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).
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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 1163 1 26 1 3 1194
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 “bupropion” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
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/.
16
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
17
The HSTAT URL is http://hstat.nlm.nih.gov/.
18
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. 19 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 20
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.
Physician Resources 185
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/.
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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 bupropion 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 bupropion. 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 bupropion. 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 “bupropion”:
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Bupropion
Other Guides Attention Deficit Disorder with Hyperactivity http://www.nlm.nih.gov/medlineplus/attentiondeficitdisorderwithhyperactivity.t ml Multiple Sclerosis http://www.nlm.nih.gov/medlineplus/multiplesclerosis.html Smokeless Tobacco http://www.nlm.nih.gov/medlineplus/smokelesstobacco.html Smoking and Youth http://www.nlm.nih.gov/medlineplus/smokingandyouth.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. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Bupropion (Wellbutrin) Summary: Bupropion (byoo-PROE-pee-on) is used to relieve mental depression and is used as part of a support program to help you stop smoking. Source: National Library of Medicine, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6997 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 bupropion. 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.
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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/
•
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 bupropion. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with bupropion. 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 bupropion. 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 “bupropion” (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
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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 “bupropion”. 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 “bupropion” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “bupropion” (or a synonym) into the search box, and click “Submit Query.”
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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.
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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 193
•
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/
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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 195
•
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/
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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
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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
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BUPROPION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-hydroxyindoleacetic acid: 5HIAA. A break-down product of serotonin that is excreted in the urine. Serotonin is a hormone found in high levels in many body tissues. Serotonin and 5HIAA are produced in excess amounts by carcinoid tumors, and levels of these substances may be measured in the urine to test for carcinoid tumors. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] 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 antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU]
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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] 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] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans.
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Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Antihypertensive: An agent that reduces high blood pressure. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiviral: Destroying viruses or suppressing their replication. [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] 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] Arthralgia: Pain in the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH]
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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] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] 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] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Aversion therapy: Negative conditioning, consisting of pairing the unwanted symptom or behavior (e. g. alcoholism) with painful or unpleasant stimuli until the undesirable behavior is suppressed. [NIH] 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]
Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] 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] Bioequivalent: Having the same strength and similar bioavailability in the same dosage form as another specimen of a given drug substance. [EU] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] 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
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engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] 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] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH]
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Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [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] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbimazole: An imidazole antithyroid agent. Carbimazole is metabolized to methimazole, which is responsible for the antithyroid activity. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogenic: Producing carcinoma. [EU] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign. [NIH]
Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and
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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] 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] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] 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] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: emphysema. [NIH]
Collective term for chronic bronchitis and
Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol
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uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]
Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] 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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] 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
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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] Compulsive Behavior: The behavior of performing an act persistently and repetitively without it leading to reward or pleasure. The act is usually a small, circumscribed behavior, almost ritualistic, yet not pathologically disturbing. Examples of compulsive behavior include twirling of hair, checking something constantly, not wanting pennies in change, straightening tilted pictures, etc. [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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [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] Constipation: Infrequent or difficult evacuation of feces. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH]
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Consumption: Pulmonary tuberculosis. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] 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 Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] 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] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
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Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, ... New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] 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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Offices: The room or rooms in which the dentist and dental staff provide care. Offices include all rooms in the dentist's office suite. [NIH] Dental Staff: Personnel who provide dental service to patients in an organized facility, institution or agency. [NIH] Dentists: Individuals licensed to practice dentistry. [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]
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Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [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] 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] Dextrorotatory: Turning towards the right hand. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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
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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] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several 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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] 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] Doxepin: A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Duke: A lamp which produces ultraviolet radiations for certain ophthalmologic therapy. [NIH]
Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or
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incomplete movements. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [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] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] 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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also
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called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
Extracellular: Outside a cell or cells. [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]
Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [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]
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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] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Forearm: The part between the elbow and the wrist. [NIH] 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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [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] Gastric Acid: Hydrochloric acid present in gastric juice. [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 are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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]
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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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanfacine: A centrally acting antihypertensive agent. The drug lowers both systolic and diastolic blood pressure by activating the central nervous system alpha-2 adrenoreceptors, which results in reduced sympathetic outflow leading to reduced vascular tone. Its adverse reactions include dry mouth, sedation, and constipation. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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] Haloperidol: Butyrophenone derivative. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH]
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Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] 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] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [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] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] 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] 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] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually
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by replacement of hydrogen. [EU] Hyperglycemia: Abnormally high blood sugar. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypnotherapy: Sleeping-cure. [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] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ibogaine: One of several indole alkaloids extracted from Tabernanthe iboga, Baill. It has a complex pharmacological profile and interacts with multiple systems of neurotransmission. Ibogaine has psychoactive properties and appears to modulate tolerance to opiates. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idazoxan: An alpha(2)-adrenoceptor antagonist. It has been used experimentally to test the binding activity of other chemicals. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune response: (antigens). [NIH]
The activity of the immune system against foreign substances
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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In 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] Induction: The act or process of inducing or causing to occur, especially the production of a
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specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [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] Involuntary: Reaction occurring without intention or volition. [NIH]
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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] Iop: Intraocular pressure: pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Isradipine: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methyl ethyl ester. A potent calcium channel antagonist that is highly selective for vascular smooth muscle. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Lactation: The period of the secretion of milk. [EU] 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]
Lesion: An area of abnormal tissue change. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: circulation. [NIH]
Services offered to the library user. They include reference and
Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [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
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the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Lipid: Fat. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobeline: An alkaloid that has actions similar to nicotine on nicotinic cholinergic receptors but is less potent. It has been proposed for a variety of therapeutic uses including in respiratory disorders, peripheral vascular disorders, insomnia, and smoking cessation. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Lubricants: Oily or slippery substances. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] 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] Maprotiline: A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Maxillary Nerve: The intermediate sensory division of the trigeminal (5th cranial) nerve. The maxillary nerve carries general afferents from the intermediate region of the face including the lower eyelid, nose and upper lip, the maxillary teeth, and parts of the dura. [NIH]
Mecamylamine: A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. [NIH]
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Medial: Lying near the midsaggital plane of the body; opposed to lateral. [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] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [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] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Menthol: An alcohol produced from mint oils or prepared synthetically. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methimazole: A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH] 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] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mianserin: A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors. [NIH]
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Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH]
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Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] 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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] 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] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]
Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not
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affect the psychic personality of the patient. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [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] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU]
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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] 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] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
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 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] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]
Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (=
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branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: simplex. [NIH]
Inflammation of the periodontal membrane; also called periodontitis
Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [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] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [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] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer
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phenotype, characteristic of yeasts. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Pilot study: The initial study examining a new method or treatment. [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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful
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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] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight
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of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prone: Having the front portion of the body downwards. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychomotor Performance: The coordination of a sensory or ideational (cognitive) process and a motor activity. [NIH] Psychosexual: Pertaining to the mental aspects of sex. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy:
A generic term for the treatment of mental illness or emotional
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disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] 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] 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] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH]
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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] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refractory: Not readily yielding to treatment. [EU] 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 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] Retrospective: Looking back at events that have already taken place. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seasonal Affective Disorder: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include
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anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (phototherapy), during the season of recurrence. [NIH] Sebaceous: Gland that secretes sebum. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] 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] 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] Serum Sickness: Immune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses. [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] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH]
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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] 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] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] 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 the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH]
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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]
Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [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]
Substrate: A substance upon which an enzyme acts. [EU] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or second-
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messenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] 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]
Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] 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]
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Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigeminal Nerve: The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. [NIH] Trimipramine: Tricyclic antidepressant similar to imipramine, but with more antihistaminic and sedative properties. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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
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the bladder, and leaves the body through the urethra. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Veins: The vessels carrying blood toward the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] 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] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [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] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [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] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the
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cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH]
239
INDEX 5 5-hydroxyindoleacetic acid, 120, 201 A Abdomen, 201, 205, 222, 236 Abdominal, 201, 227, 230 Acceptor, 201, 227 Acetylcholine, 104, 126, 201, 207 Adenocarcinoma, 201, 226 Adjustment, 3, 201 Adjuvant, 201, 216 Adrenal Medulla, 201, 206, 214, 226 Adrenergic, 11, 153, 154, 155, 156, 157, 165, 201, 202, 213, 214, 223, 231, 236, 238 Adverse Effect, 11, 140, 172, 201, 234 Afferent, 201, 230 Affinity, 147, 201, 202, 204, 212, 235 Agonist, 202, 205, 213, 226 Agoraphobia, 202, 219, 227, 229 Alertness, 146, 148, 158, 160, 163, 202 Algorithms, 202, 205 Alkaloid, 202, 205, 208, 222, 226 Alpha-1, 202 Alternative medicine, 175, 202 Amantadine, 85, 202 Ameliorated, 147, 162, 202 Amenorrhea, 202, 205 Amitriptyline, 60, 61, 69, 90, 92, 129, 202 Amnestic, 202, 216 Amphetamine, 65, 66, 72, 76, 84, 93, 141, 202, 212 Anaesthesia, 202, 220 Anatomical, 202, 219, 233 Angina, 202, 221, 231 Angina Pectoris, 202, 221, 231 Animal model, 147, 163, 202 Anomalies, 203, 224 Antagonism, 203, 213 Antibody, 201, 203, 208, 217, 220, 223, 234, 235 Anticholinergic, 161, 202, 203, 213 Anticonvulsant, 69, 203 Antidepressant, 5, 63, 67, 76, 82, 84, 85, 88, 89, 91, 95, 100, 101, 105, 106, 116, 119, 124, 130, 140, 141, 146, 147, 148, 149, 150, 151, 152, 158, 159, 160, 161, 163, 165, 166, 171, 202, 203, 206, 207, 216, 219, 222, 223, 238, 239 Antidote, 71, 203
Antiemetic, 203, 223 Antigen, 201, 203, 208, 219, 220, 223 Antihypertensive, 8, 203, 217 Antioxidant, 203 Antiviral, 202, 203, 225 Anxiety, 66, 86, 93, 104, 108, 109, 119, 203, 216, 227, 229, 231, 234 Anxiety Disorders, 203, 227 Aqueous, 155, 203, 204 Arteries, 203, 205, 210, 223, 225 Arterioles, 203, 205, 225 Arthralgia, 203, 234 Articular, 100, 203, 221 Ascorbic Acid, 159, 161, 166, 203 Aspartate, 204, 221, 228 Assay, 84, 204 Astrocytes, 204, 224 Atopic, 118, 204 Atypical, 98, 102, 109, 204, 226 Auditory, 66, 120, 204, 230 Autoimmune disease, 204, 224 Autonomic, 96, 152, 201, 204, 216, 226, 236 Aversion therapy, 8, 204 B Bactericidal, 204, 215 Base, 6, 8, 139, 146, 158, 204, 211, 221 Behavior Therapy, 88, 204 Benign, 204, 206, 216, 217 Bereavement, 4, 80, 173, 204 Bile, 204, 216, 222 Bioavailability, 204 Biochemical, 8, 75, 204, 234 Bioequivalent, 148, 204 Biological Transport, 204, 212 Biotechnology, 58, 59, 175, 183, 204 Bipolar Disorder, 4, 67, 76, 99, 118, 129, 141, 205 Bladder, 205, 219, 224, 238, 239 Blastocyst, 205, 209 Blood Cell Count, 140, 205, 217 Blood Glucose, 4, 205, 218 Blood Platelets, 205, 234 Blood pressure, 4, 203, 205, 206, 216, 219, 224, 228, 235 Blood vessel, 4, 140, 205, 206, 207, 228, 234, 236, 237, 239 Blood-Brain Barrier, 205, 221, 222 Body Fluids, 205, 235
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Body Mass Index, 205, 227 Bone Marrow, 205, 210, 222 Bowel, 205, 212, 221, 236 Bowel Movement, 205, 212, 236 Brain Stem, 205, 238 Branch, 197, 205, 226, 228, 232, 235 Breast Feeding, 6, 205 Bromocriptine, 104, 126, 205 Bronchi, 205, 206, 214 Bronchitis, 11, 206, 207 Buccal, 206, 222 Bulimia, 117, 118, 206 C Calcium, 206, 208, 221 Capsules, 150, 160, 206, 213, 215, 216 Carbimazole, 65, 206 Carbohydrate, 85, 206, 229, 234 Carcinogenic, 206, 220 Carcinoid, 201, 206 Carcinoma, 206, 226, 235 Cardiac, 90, 110, 206, 214, 221, 225 Cardiac arrest, 110, 206 Cardioselective, 206, 231 Cardiovascular, 11, 71, 79, 87, 114, 153, 155, 161, 169, 202, 206, 234 Cardiovascular disease, 79, 169, 206 Case report, 65, 67, 68, 71, 76, 82, 92, 118, 206, 208 Case series, 78, 91, 206, 208 Catecholamine, 206, 213, 228 Cell, 137, 202, 204, 205, 207, 209, 215, 216, 220, 225, 226, 227, 229, 232, 234, 236, 237 Cellobiose, 207 Cellulose, 148, 149, 151, 152, 155, 166, 207, 223, 229 Central Nervous System, 201, 202, 207, 208, 212, 216, 217, 221, 223, 224, 228, 234 Central Nervous System Infections, 207, 217 Centrifugation, 207, 217, 224 Cerebral, 147, 162, 205, 207, 210, 211, 214, 215, 216, 231 Cerebrospinal, 120, 207 Cerebrospinal fluid, 120, 207 Cerebrovascular, 11, 206, 207 Cerebrum, 207 Character, 202, 207, 211 Cholesterol, 4, 148, 163, 204, 207, 210 Cholinergic, 202, 207, 222, 226 Chronic, 3, 5, 7, 8, 64, 75, 82, 110, 125, 153, 154, 164, 207, 220, 221, 222, 231, 234, 236, 239
Chronic Disease, 5, 8, 207 Chronic Fatigue Syndrome, 75, 82, 154, 164, 207 Chronic Obstructive Pulmonary Disease, 110, 207 Cimetidine, 101, 207 Citalopram, 140, 207 Citric Acid, 159, 161, 166, 208 Citrus, 203, 208 Clear cell carcinoma, 208, 212 Clinical study, 208, 210 Clinical trial, 11, 60, 97, 103, 107, 110, 137, 142, 183, 208, 210, 224, 228, 232 Cloning, 205, 208 Coca, 208 Cocaine, 63, 66, 78, 81, 96, 104, 125, 126, 208 Coenzyme, 203, 208 Cognition, 4, 208 Combination Therapy, 101, 120, 126, 208 Complement, 208, 209 Complementary and alternative medicine, 129, 133, 209 Complementary medicine, 129, 209 Complete remission, 209, 233 Compulsive Behavior, 69, 209 Computational Biology, 183, 209 Conception, 12, 209, 210 Conduction, 90, 94, 209 Congestion, 209, 215 Congestive heart failure, 87, 209 Conjugated, 209, 211 Conjunctiva, 209, 238 Connective Tissue, 203, 205, 209, 216, 233 Consciousness, 209, 211, 213 Constipation, 209, 217 Consultation, 4, 8, 209 Consumption, 97, 148, 163, 210 Contraceptive, 11, 210 Contraindications, ii, 169, 210 Controlled clinical trial, 61, 210 Controlled study, 75, 78, 210 Convulsions, 203, 210, 214, 219 Coordination, 210, 224, 231 Coronary, 11, 202, 206, 210, 223, 225 Coronary Arteriosclerosis, 210, 225 Coronary Circulation, 202, 210 Coronary heart disease, 206, 210 Coronary Thrombosis, 210, 223, 225 Cortical, 210, 230, 234 Cranial, 210, 217, 222, 238 Craniocerebral Trauma, 210, 217
Index 241
Creatinine, 160, 210 Cutaneous, 210, 222 Cyclic, 76, 210 Cyclosporine, 105, 210 Cysteine, 148, 149, 151, 152, 159, 161, 162, 166, 210 Cystine, 159, 161, 166, 210 Cytochrome, 98, 120, 207, 211 D Databases, Bibliographic, 183, 211 Deamination, 211, 224 Degenerative, 211, 218 Delirium, 59, 65, 69, 92, 153, 211 Delivery of Health Care, 211, 217 Delusions, 107, 211, 231 Density, 205, 207, 211, 229, 235 Dental Offices, 10, 211 Dental Staff, 211 Dentists, 10, 211 Depersonalization, 211, 227, 233 Depressive Disorder, 4, 66, 76, 94, 108, 141, 211, 222 Derealization, 211, 212, 227 Dermatitis, 118, 212 DES, 127, 212 Desipramine, 62, 212 DEXA, 60, 96, 129, 212 Dextroamphetamine, 60, 202, 212, 223 Dextrorotatory, 153, 154, 155, 156, 157, 164, 165, 212 Diagnostic procedure, 145, 175, 212 Diastolic, 212, 217, 219 Diastolic blood pressure, 212, 217 Diencephalon, 212, 230, 237 Diffusion, 149, 151, 152, 204, 212 Digestion, 204, 205, 212, 222, 236 Digestive system, 143, 212 Dimethyl, 163, 212, 221 Direct, iii, 6, 155, 212, 213, 233 Disinfectant, 212, 215 Disorientation, 211, 212, 213 Disposition, 91, 93, 98, 109, 115, 120, 212 Dissociation, 201, 212 Dizziness, 213, 227 Dopa, 213, 221 Dopamine, 77, 91, 95, 124, 125, 130, 131, 141, 147, 163, 202, 205, 206, 208, 212, 213, 221, 223, 224 Dorsal, 213, 215 Dosage Forms, 159, 166, 167, 213 Doxepin, 94, 213 Drive, ii, vi, 10, 123, 213, 221
Drug Delivery Systems, 155, 213 Drug Interactions, 69, 91, 109, 213 Drug Monitoring, 78, 88, 112, 113, 117, 213 Duke, 124, 213 Dyes, 213, 226, 236 Dyskinesia, 109, 146, 148, 158, 160, 163, 208, 213 Dysphoric, 90, 211, 214 Dyspnea, 214, 227 Dystonia, 85, 214 Dystrophy, 154, 164, 214 E Effector, 201, 208, 214, 226 Electroconvulsive Therapy, 71, 214 Electrolyte, 211, 214, 229, 235 Electrons, 203, 204, 214, 221, 227, 232 Electroplating, 214, 236 Embolus, 214, 220 Embryo, 205, 214, 220 Emphysema, 11, 207, 214 Environmental Health, 182, 184, 214 Enzyme, 208, 214, 223, 224, 228, 231, 236, 239 Eosinophilia, 94, 98, 214 Eosinophils, 214, 221 Epidermis, 214, 232 Epinephrine, 201, 213, 214, 226, 238 Erectile, 70, 214, 215 Erection, 214, 215 Ergot, 205, 215 Erythema, 85, 98, 101, 173, 215, 239 Erythema Multiforme, 85, 101, 173, 215 Erythrocyte Indices, 205, 215 Erythrocytes, 205, 215 Esophagus, 212, 215, 236 Estrogen, 215, 231 Ethanol, 146, 148, 156, 158, 160, 163, 207, 215 Evoke, 215, 235 Excipient, 149, 151, 152, 165, 215 Extensor, 215, 231 Extracellular, 204, 209, 215, 235 Extrapyramidal, 202, 213, 215 F Family Planning, 183, 215 Fat, 205, 210, 212, 214, 215, 222, 224, 227, 233 Fatigue, 3, 74, 207, 215, 217, 228 Fertilizers, 215, 226, 236 Filler, 155, 215 Fissure, 215, 230
242
Bupropion
Fluoxetine, 63, 82, 89, 90, 93, 99, 100, 105, 113, 118, 140, 153, 216 Fluvoxamine, 140, 216 Forearm, 205, 216 Frontal Lobe, 216, 230 G Gallbladder, 201, 212, 216 Ganglia, 201, 216, 219, 222, 225, 236 Ganglion, 216, 238 Ganglionic Blockers, 216, 222 Gas, 212, 216, 218, 220, 226, 239 Gastric, 11, 155, 207, 213, 216, 218, 228 Gastric Acid, 207, 216 Gastrin, 207, 216, 218 Gastrointestinal, 152, 206, 214, 215, 216, 222, 234, 236 Gastrointestinal tract, 152, 215, 216, 222, 234 Gelatin, 216, 217 Gene, 205, 216 Genotype, 216, 228 Gestation, 12, 216 Gland, 201, 216, 219, 227, 234, 235 Glucose, 203, 205, 207, 216, 218, 219 Glycine, 150, 159, 161, 162, 166, 217 Governing Board, 217, 230 Growth, 72, 99, 100, 116, 203, 215, 217, 229, 238 Guanfacine, 69, 110, 111, 217 H Hair follicles, 217, 239 Half-Life, 146, 158, 217 Hallucinogen, 217, 228 Haloperidol, 90, 130, 217 Haptens, 201, 217, 234 Headache, 119, 217, 219, 230 Headache Disorders, 217 Health Care Costs, 139, 217 Health Expenditures, 217 Heart attack, 206, 217 Heart failure, 217 Hematocrit, 205, 215, 217 Heme, 211, 217 Hemoglobin, 205, 215, 217, 218 Hemorrhage, 210, 217, 218, 236 Hemostasis, 218, 234 Hepatic, 211, 218, 224 Hepatitis, 65, 218 Hepatocytes, 218 Herpes, 147, 163, 218 Herpes Zoster, 218 Heterogeneity, 201, 218
Histamine, 207, 213, 218, 223 Hormone, 72, 99, 100, 116, 201, 212, 214, 216, 218, 230, 233 Hydrochloric Acid, 161, 162, 166, 218 Hydrogen, 201, 204, 206, 218, 219, 224, 227 Hydrolysis, 166, 207, 218, 229 Hydrophilic, 165, 218 Hydrophobic, 165, 218 Hydroxylation, 91, 98, 120, 218 Hyperglycemia, 4, 219 Hypersensitivity, 85, 219, 233 Hypertension, 206, 217, 219, 221, 222, 231 Hyperthyroidism, 219, 231 Hypnotherapy, 8, 219 Hypoglycaemia, 211, 219 Hypokinesia, 219, 227 Hypotension, 65, 119, 210, 216, 219 Hypoxia, 211, 219 I Ibogaine, 104, 126, 219 Id, 127, 132, 191, 196, 198, 219 Idazoxan, 61, 219 Imidazole, 206, 218, 219 Imipramine, 64, 87, 89, 90, 219, 238, 239 Immune response, 201, 203, 204, 217, 219, 236, 239 Immunology, 75, 94, 201, 219 Impairment, 86, 146, 158, 160, 211, 213, 219, 223, 231 Implantation, 209, 219 Impotence, 215, 219 In vitro, 91, 109, 148, 219 In vivo, 219 Incontinence, 147, 162, 219 Induction, 76, 141, 216, 219, 221, 231 Infarction, 7, 220 Infection, 85, 147, 163, 211, 220, 222, 233, 236, 239 Infertility, 205, 220 Inflammation, 206, 212, 218, 220, 228, 233, 235, 239 Ingestion, 66, 146, 158, 160, 220, 229 Inhalation, 10, 220, 229 Initiation, 7, 220 Innervation, 213, 220 Inorganic, 160, 161, 162, 166, 220 Inotropic, 213, 220 Inpatients, 61, 220 Insomnia, 220, 222, 230, 238 Insufflation, 111, 220 Insulator, 220, 224 Interpersonal Relations, 4, 220
Index 243
Intervertebral, 220, 222 Intervertebral Disk Displacement, 220, 222 Intestines, 201, 216, 220 Intoxication, 68, 211, 220, 240 Intracellular, 220, 229, 232 Intrinsic, 201, 220 Involuntary, 220, 225, 233 Ions, 204, 212, 214, 218, 221, 224 Iop, 126, 221 Isradipine, 155, 221 J Joint, 4, 203, 221, 235 K Kb, 182, 221 Ketamine, 221, 228 Kinetics, 102, 221 L Lactation, 221, 231 Large Intestine, 212, 220, 221, 232, 234 Laxative, 221, 223 Lesion, 130, 221, 237 Leukocytes, 205, 214, 221 Levodopa, 89, 213, 221 Libido, 86, 221 Library Services, 196, 221 Ligaments, 210, 221 Limbic, 221, 230 Limbic System, 221, 230 Lipid, 222, 224 Lithium, 4, 115, 222 Liver, 65, 93, 98, 201, 204, 212, 216, 218, 222, 224 Lobeline, 8, 222 Localized, 220, 222, 224, 229, 239 Low Back Pain, 75, 222 Lubricants, 155, 222 Lumbar, 220, 222 Lupus, 3, 222 Lutein Cells, 222, 231 Lymph, 222, 234 Lymphadenopathy, 222, 234 Lymphatic, 220, 222 M Mania, 4, 70, 85, 92, 102, 106, 141, 222 Manic, 76, 205, 222, 231 Manic-depressive psychosis, 222, 231 Maprotiline, 103, 222 Mastication, 222, 238 Maxillary, 222, 238 Maxillary Nerve, 222, 238 Mecamylamine, 8, 138, 222
Medial, 130, 223 Mediate, 213, 223 Mediator, 213, 223, 234 MEDLINE, 10, 183, 223 Membrane, 161, 204, 209, 215, 223, 224, 227, 228 Memory, 211, 223 Menopause, 223, 231 Menstrual Cycle, 223, 230 Menstruation, 202, 223, 230 Mental Disorders, 104, 143, 219, 223, 231 Mental Health, iv, 124, 138, 141, 143, 182, 186, 223, 232 Menthol, 131, 223 Metabolite, 98, 146, 158, 212, 223, 226 Methimazole, 206, 223 Methionine, 212, 223 Methylcellulose, 148, 149, 156, 223 Methylphenidate, 79, 83, 86, 93, 105, 175, 223 Metoclopramide, 104, 223 MI, 199, 223 Mianserin, 103, 223 Microbe, 224, 237 Microbiology, 204, 224 Microsomal, 98, 224 Mobility, 4, 224 Modification, 7, 119, 224, 232 Molecular, 103, 156, 183, 186, 204, 209, 224, 230, 232, 238 Molecular Structure, 224, 238 Molecule, 153, 154, 155, 156, 157, 164, 165, 203, 204, 208, 212, 214, 218, 224, 227, 232 Monitor, 210, 224 Monoamine, 4, 147, 162, 163, 202, 212, 224, 238 Monoamine Oxidase, 147, 163, 202, 212, 224, 238 Monotherapy, 89, 224 Mood Disorders, 3, 76, 124, 153, 224 Motility, 224, 234 Motion Sickness, 224, 225 Motor Activity, 210, 224, 231 Mucosa, 222, 224, 231 Multicenter Studies, 119, 224 Multicenter study, 224 Multiple sclerosis, 74, 224 Muscular Dystrophies, 214, 225 Myelin, 224, 225 Myocardial infarction, 7, 65, 210, 223, 225, 231 Myocardial Ischemia, 66, 202, 225
244
Bupropion
Myocardium, 202, 223, 225 N Narcolepsy, 109, 154, 164, 212, 223, 225 Nausea, 104, 203, 213, 225, 227, 230 NCI, 1, 137, 142, 181, 225 Necrosis, 220, 223, 225 Need, 3, 5, 6, 7, 9, 12, 146, 152, 169, 176, 184, 192, 225, 237 Nelfinavir, 91, 109, 225 Nerve, 201, 202, 216, 220, 222, 223, 224, 225, 233, 235, 237, 238 Nervous System, 201, 202, 207, 223, 225, 226, 230, 236, 237, 238 Neural, 201, 212, 216, 224, 225 Neuromuscular, 201, 225 Neuromuscular Junction, 201, 225 Neuronal, 147, 162, 163, 207, 225 Neurons, 208, 216, 221, 225, 226, 236 Neurosis, 225, 229 Neurotoxicity, 85, 226 Neurotransmitters, 202, 213, 226, 230 Niacin, 226, 238 Nitric acid, 161, 162, 166, 226 Nitrogen, 202, 226, 238 Non-small cell lung cancer, 137, 226 Nonverbal Communication, 226, 232 Norepinephrine, 95, 124, 130, 141, 147, 201, 202, 212, 213, 226 Nortriptyline, 4, 8, 12, 83, 104, 114, 170, 226 Nucleus, 210, 214, 220, 226, 230, 238 O Office Visits, 6, 226 Ointments, 213, 226 Ophthalmic, 226, 238 Ophthalmologic, 213, 226 Oral Health, 10, 226 Orgasm, 86, 113, 226 Orthostatic, 65, 119, 226 Osmosis, 227 Osmotic, 149, 151, 152, 155, 227 Outpatient, 7, 119, 139, 227 Overdose, 64, 77, 87, 94, 99, 113, 114, 118, 227 Overweight, 74, 124, 127, 173, 227 Ovum, 216, 227, 230, 231, 240 Oxidation, 166, 201, 203, 210, 211, 223, 227 P Pancreas, 201, 212, 227 Panic, 101, 105, 216, 219, 227 Panic Disorder, 101, 216, 219, 227 Paresthesias, 227
Parkinsonism, 65, 69, 221, 227 Paroxetine, 67, 81, 89, 90, 105, 140, 227 Paroxysmal, 202, 217, 227 Partial remission, 227, 233 Parturition, 227, 231 Patch, 4, 6, 8, 9, 11, 61, 77, 91, 101, 103, 124, 125, 126, 138, 142, 158, 169, 175, 176, 227, 237 Pathologic, 210, 219, 227, 231 Patient Selection, 169, 228 Pemoline, 88, 228 Pepsin, 207, 228 Pepsin A, 207, 228 Periodontal disease, 228 Periodontitis, 10, 228 Peripheral Vascular Disease, 11, 228 Pharmaceutical Preparations, 160, 161, 166, 207, 215, 216, 228 Pharmaceutical Solutions, 213, 228 Pharmacist, 119, 228 Pharmacokinetic, 89, 105, 107, 228 Pharmacologic, 4, 7, 8, 9, 12, 72, 112, 114, 116, 138, 142, 217, 228, 237 Phencyclidine, 104, 126, 228 Phenotype, 78, 88, 228 Phobia, 86, 119, 229 Phobic Disorders, 229 Phototherapy, 229, 234 Physiologic, 202, 213, 217, 219, 223, 229, 232, 238 Pilot study, 66, 74, 92, 95, 104, 118, 126, 139, 140, 229 Plants, 202, 208, 216, 226, 229, 237 Plasma, 62, 67, 72, 78, 92, 95, 98, 100, 107, 113, 162, 216, 218, 229 Platelets, 95, 98, 140, 229, 237 Poisoning, 78, 211, 215, 220, 225, 229 Polyethylene, 148, 155, 229 Polymers, 166, 229, 231 Polypeptide, 228, 229, 230 Polysaccharide, 203, 207, 229 Postherpetic Neuralgia, 202, 229 Potassium, 160, 229 Potentiates, 212, 229 Potentiating, 202, 230 Practicability, 230, 238 Practice Guidelines, 186, 230 Precipitation, 106, 230 Precursor, 213, 214, 221, 226, 230, 238 Prefrontal Cortex, 130, 230 Premenstrual, 90, 154, 164, 230 Premenstrual Syndrome, 154, 164, 230
Index 245
Presynaptic, 213, 230, 236 Presynaptic Terminals, 213, 230 Prevalence, 6, 107, 139, 230 Problem Solving, 8, 230 Progesterone, 230, 231 Progression, 10, 203, 230 Progressive, 217, 225, 230, 233 Projection, 226, 230 Prolactin, 72, 99, 100, 115, 116, 148, 160, 163, 205, 230 Prone, 166, 231 Propranolol, 153, 154, 155, 156, 157, 164, 165, 231 Prospective study, 59, 70, 231 Protease, 208, 225, 231, 233 Protein C, 231, 234 Protein S, 205, 231 Proteins, 203, 208, 224, 226, 228, 229, 231, 232, 234, 237 Psoriasis, 100, 118, 231 Psychiatric, 95, 98, 125, 223, 231, 234 Psychic, 221, 226, 231, 234 Psychomotor, 116, 211, 231 Psychomotor Performance, 116, 231 Psychosexual, 146, 148, 158, 160, 163, 231 Psychosis, 4, 66, 86, 107, 231, 232 Psychotherapy, 4, 66, 231 Psychotomimetic, 202, 212, 232 Public Health, 5, 8, 139, 169, 186, 232 Public Policy, 183, 232 Publishing, 58, 232 Pulmonary, 205, 210, 232 Pulmonary Artery, 205, 232 Pustular, 100, 232 Q Quality of Life, 4, 232 R Race, 147, 153, 154, 155, 156, 157, 163, 164, 165, 213, 232 Radiation, 202, 212, 232 Radioactive, 217, 218, 219, 232 Randomized, 63, 78, 94, 114, 137, 139, 185, 214, 232 Randomized clinical trial, 232 Reagent, 218, 232 Reality Testing, 231, 232 Receptor, 104, 126, 155, 203, 213, 232, 234 Receptors, Serotonin, 232, 234 Rectum, 205, 212, 216, 219, 221, 232 Recur, 232, 233 Recurrence, 205, 222, 232, 233, 234 Refer, 1, 5, 206, 208, 213, 218, 231, 233
Reflex, 154, 164, 233 Refractory, 82, 83, 87, 105, 233 Regimen, 167, 214, 228, 233 Relapse, 5, 8, 11, 72, 91, 93, 96, 103, 114, 142, 172, 173, 185, 233 Remission, 8, 108, 205, 222, 233 Renal failure, 211, 233 Retrospective, 64, 77, 108, 233 Rheumatic Diseases, 3, 233 Rheumatism, 233 Rheumatoid, 3, 233 Rheumatoid arthritis, 3, 233 Rigidity, 227, 229, 233 Risk factor, 231, 233 Ritonavir, 91, 109, 233 S Salivary, 212, 233 Salivary glands, 212, 233 Schizoid, 233, 239 Schizophrenia, 63, 97, 214, 233, 239 Schizotypal Personality Disorder, 211, 233, 239 Sclerosis, 190, 224, 233 Screening, 7, 78, 208, 233 Seasonal Affective Disorder, 154, 164, 233 Sebaceous, 234, 239 Secretion, 116, 148, 160, 163, 205, 207, 218, 221, 234 Sedative, 130, 202, 219, 234, 238 Seizures, 59, 68, 71, 78, 86, 100, 111, 149, 150, 151, 152, 153, 211, 227, 234 Semisynthetic, 205, 234 Sertraline, 63, 67, 90, 93, 98, 108, 112, 113, 140, 141, 234 Serum, 59, 62, 68, 70, 75, 86, 111, 112, 117, 208, 234 Serum Sickness, 59, 68, 70, 75, 86, 234 Side effect, 8, 67, 81, 82, 86, 90, 102, 149, 151, 152, 153, 169, 201, 207, 222, 234, 237 Signs and Symptoms, 233, 234 Skeleton, 221, 234 Sleep Deprivation, 111, 234 Small cell lung cancer, 137, 234 Small intestine, 218, 220, 234 Smooth muscle, 218, 221, 234, 236 Social Environment, 232, 234 Sodium, 149, 151, 152, 159, 161, 162, 166, 235 Solvent, 215, 227, 228, 235 Somatic, 221, 230, 235 Sound wave, 209, 235 Specialist, 9, 191, 235
246
Bupropion
Species, 106, 214, 232, 235, 236, 238, 239, 240 Specificity, 201, 235 Spinal cord, 204, 205, 207, 216, 225, 233, 235, 236 Sprains and Strains, 222, 235 Squamous, 226, 235 Squamous cell carcinoma, 226, 235 Stabilization, 159, 162, 235 Stabilizer, 118, 148, 149, 150, 151, 152, 159, 160, 162, 165, 235 Steroids, 100, 235 Stimulant, 202, 212, 218, 223, 228, 235 Stimulus, 93, 126, 213, 220, 227, 229, 233, 235 Stomach, 201, 212, 215, 216, 218, 220, 225, 228, 234, 236 Stool, 219, 221, 236 Stress, 3, 4, 10, 64, 82, 207, 225, 233, 236, 239 Stroke, 143, 174, 182, 206, 236 Subacute, 220, 236 Subarachnoid, 217, 236 Subclinical, 220, 234, 236 Subspecies, 235, 236 Substance P, 223, 234, 236 Substrate, 236, 238 Sulfuric acid, 161, 162, 166, 236 Sympathetic Nervous System, 236 Sympathomimetic, 161, 202, 212, 213, 214, 226, 236, 238 Symptomatic, 202, 236 Symptomatic treatment, 202, 236 Synaptic, 226, 236 Synaptic Transmission, 226, 236 Synergistic, 231, 237 Systemic, 3, 94, 205, 211, 214, 220, 237 Systolic, 217, 219, 237 T Tardive, 146, 148, 158, 160, 163, 208, 237 Thalamus, 212, 221, 230, 237 Thiamine, 160, 237 Thrombocytes, 229, 237 Thrombosis, 231, 236, 237 Thrombus, 210, 220, 225, 237 Tissue, 118, 203, 204, 205, 206, 209, 214, 215, 219, 221, 223, 225, 234, 235, 237 Tolerance, 219, 237 Tonicity, 214, 237 Topical, 215, 237 Torsion, 220, 237 Toxic, iv, 226, 237
Toxicity, 68, 104, 213, 237 Toxicology, 62, 66, 87, 94, 99, 106, 117, 118, 126, 184, 237 Toxins, 203, 220, 237 Transdermal, 8, 10, 11, 139, 146, 158, 237 Transfection, 205, 237 Transmitter, 201, 204, 213, 223, 226, 237, 238 Trauma, 211, 225, 238 Treatment Outcome, 10, 238 Tremor, 227, 238 Triazolam, 93, 238 Tricyclic, 4, 76, 97, 100, 119, 146, 153, 158, 165, 202, 208, 212, 213, 219, 222, 238 Trigeminal, 86, 222, 238 Trigeminal Nerve, 86, 238 Trimipramine, 111, 238 Tryptophan, 96, 234, 238 Tuberculosis, 210, 222, 238 Tyramine, 99, 224, 238 Tyrosine, 213, 238 U Unconscious, 219, 238 Urethra, 238, 239 Urinary, 219, 238 Urine, 76, 201, 205, 210, 219, 238 Urticaria, 69, 234, 239 V Vaccine, 201, 239 Vagina, 212, 223, 239 Vascular, 217, 220, 221, 222, 237, 239 Vasodilator, 213, 218, 239 VE, 82, 139, 239 Veins, 205, 239 Venlafaxine, 67, 89, 90, 102, 103, 115, 119, 120, 131, 141, 239 Venous, 205, 231, 239 Venous blood, 205, 239 Ventricles, 207, 239 Venules, 205, 239 Vesicular, 218, 224, 239 Veterinary Medicine, 183, 239 Viloxazine, 103, 239 Viral, 147, 163, 239 Virulence, 237, 239 Virus, 147, 163, 207, 239 Vitro, 239 Vulgaris, 118, 239 W Wakefulness, 211, 239 Weight Gain, 85, 156, 164, 173, 174, 176, 234, 239
Index 247
Withdrawal, 5, 6, 72, 80, 115, 125, 126, 130, 146, 152, 158, 176, 211, 239 X Xenograft, 203, 240
Y Yeasts, 229, 240 Z Zygote, 209, 240
248
Bupropion
