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Acamprosate in Relapse Prevention of Alcoholism Springer Berlin Heidelberg New York Barcelona Budapest Hong Kong London Milan Paris Santa Clara Singapore Tokyo M. Soyka (Ed.) Acamprosate in Relapse Prevention of Alcoholism With 47 Figures and 16 Tables , Springer PD Dr. Michael Soyka Psychiatrische Klinik und Poliklinik der Universitat Miinchen NuBbaumstr. 7 80336 Miinchen, Germany ISBN-13 :978-3-642-80195-2 e-ISBN-13 :978-3-642-80193-8 DOl: 10.1007/978-3-642-80193-8 Library of Congress Cataloging-in-Publication Data. Acamprosate in relapse prevention of alcoholism! M.Soyka,ed. p. cm. Includes bibliographical references and index. ISBN-13:978-3-642-80195-2 (hardcover)!. Alcoholism - Chemotherapy. 2. Acamprosate. 3. Alcoholism - Relapse - Chemoprevention. I. Soyka. M. (Michael). 1959- . RC565.A27 1996 96-12923 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1996 Softcover reprint of the hardcover 1s t edition 1996 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regnlations and therefore free for general use. Product liability: The publisher cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consnlting the relevant literature. Cover design: Design & Production, Heidelberg Typesetting: Scientific Publishing Services (P) Ltd, Madras SPIN: 10525036 25!3134!SPS - 5 4 3 2 1 0 - Printed on acid-free paper Preface Alcoholism is the most common psychiatric disorder in most developed countries and a large number of developing countries, as numerous epide miological and clinical studies have demonstrated. Alcoholism affects the pa tient's life in many ways and may induce various medical and psychiatric sequelae. Over the past few decades, there have been continued efforts to improve the treatment of alcoholics. Thus different psychotherapeutic ap proaches have been designed and applied to alcohol treatment. Follow-up studies have demonstrated alcohol treatment to be efficient, with a significant number of patients remaining abstinent. Still, even after long-term inpatient treatment, more than 50% of the patients relapse. Relapse prevention remains a major challenge in the treatment of alcohol ism. Various forms of relapse prevention including group therapy, individual psychotherapy with supportive or behavioral therapy, contingency contracting, and self-help groups have been advocated. All seem to be helpful in some cases and unsuccessful in a significant number of others. Apart from chemical aversion therapy, various psychopharmacological in terventions have been tried for relapse prevention, all with limited or no success. In recent years, our knowledge of the neurochemical and neurobio logical basis of alcoholism and craving for alcohol has increased significantly. The glutamatergic system has been a major focus, and acamprosate, a mod ulator of the glutamatergic system, is one of the most promising new phar macological agents used in relapse prevention of alcoholism. In September 1995, a satellite symposium was held prior to the ESBRA congress to evaluate and discuss preclinical and clinical studies conducted with acamprosate. The proceedings of this symposium are summarized in this book, which also contains some important new papers on the pharmacology and clinical efficacy of acamprosate. The editor feels that this book offers a comprehensive overview on the most important studies on acamprosate conducted so far. It is hoped that many patients will benefit from anticraving drugs such as acamprosate, and perhaps this agent will help improve the treatment outcome in alcoholic patients. Munich Michael Soyka February 1996 Contents Ethanol and the NMDA Receptor: Implications for Intoxication, Tolerance, Dependence, and Alcoholic Brain Damage D.M. Lovinger ......................................... 1 The Neurobiology of Craving: Potential Mechanisms for Acamprosate J. Littleton, M. al Qatari, and H. Little .. . . . . . . . . . . . . . . . . . . . . . . 27 Pharmacodynamics and Pharmacokinetics of Acamprosate: An Overview P. Durbin, T. Hulot, and S. Chabac .......................... 47 Actions of Acamprosate on Neurons of the Central Nervous System W. Zieglgansberger, C. Hauser, C. Wetzel, J. Putzke, G.R. Siggins, and R. Spanagel .............................. 65 Acamprosate Decreases Alcohol Behavioral Dependence and Hypermotility After Alcohol Withdrawal But Increases Inhibitory Amino-Acids in Alcohol-Attracted Inbred Rats Using Microdialysis of the Nucleus Accumbens P. De Witte, A. Dahchour, E. Quertemont, P. Durbin, and S. Chabac ......................................... 71 Event-Related Potentials and EEG as Indicators of Central Neurophysiological Effects of Acamprosate U. Hegerl, M. Soyka, J. Gallinat, S. Ufer, U. PreuB, R. Bottlender, and H.-J. Moller ............................. 93 Effects of Acamprosate on Verbal Learning in Healthy Young Subjects N. Kathmann, M. Soyka, J. Gallinat, and U. Hegerl . . . . . . . . . . . . . . . 105 Acamprosate in Clinical Practice: The French Experience H.-J. Aubin ........................................... 111 VIII Contents Acamprosate Clinical Trials: Methodological Considerations for Assessment of Drinking Behaviour A.S. Potgieter and P. Lehert ............................... 121 Acamprosate in the Treatment of Alcohol Dependence: A 6-Month Postdetoxification Study o. I. Pelc, Le Bon, P. Lehert, and P. Verbanck ................. 133 Contribution of Acamprosate in Maintaining Abstinence in Weaned Alcohol-Dependent Patients: Additional Results of the Second French Multicentre Study F. Paille, P. Parot, and C. Gillet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 Clinical Efficacy of Acamprosate in the Treatment of Alcoholism M. Soyka ............................................. 155 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173 List of Contributors al Qatari, M., Pharmacology Group, Kings College, Manresa Road, London SW3 6LX, UK Aubin, H.-J., Centre d'Alcoologie, Hopital Emile Roux, 94456 Limeil-Brevannes Cedex, France Bottlender, R., Psychiatrische Klinik der Ludwig-Maximilians-Universitat, NuBbaumstr. 7, 80336 Munchen, Germany Chabac, S., Groupe LIPHA, DiMI, 34 rue St-Romain, 69379 Lyon Cedex 8, France Dahchour, A., Laboratoire de Psychobiologie, Universite de Louvain, Place Croix-du-Sud, 1348 Louvain-Ia-Neuve, Belgium De Witte, P., Laboratoire de Psychobiologie, Universite de Louvain, Place Croix-du-Sud, 1348 Louvain-Ia-Neuve, Belgium Durbin, P., Groupe LIPHA, Centre de Recherche et de Developpement, 115 avenue Lacassagne, 69003 Lyon, France Gallinat, J., Psychiatrische Klinik der Ludwig-Maximillians-Universitat, NuBbaumstr. 7, 80336 Munchen, Germany Gillet, C., Centre d'A lcoologie, Hopital Fournier, 36 quai de la Bataille, 54035 NancyCedex, France Hauser, C., Max-Planck-Institut fUr Psychiatrie, Klinisches Institut, Kraepelinstr. 2, 80804 Munchen, Germany Hegerl, U., Psychiatrische Klinik der Ludwig-Maximilians-Universitat, Nuf3baumstr. 7, 80336 Munchen, Germany Hulot, T., Groupe LIPHA, Centre de Recherche et de Developpement, 115 avenue Lacassagne, 69003 Lyon, France Kathmann, N., Psychiatrische Klinik der Ludwig-Maximilians-Universitat, NuBbaumstr. 7, 80336 Munchen, Germany x List of Contributors Le Bon, 0., Laboratoire de Psychobiologie Medicale et d' Alcoologie, Universite Libre de Bruxelles (Campus Brugmann), Place Van Gehuchten 4, 1020 Brussels, Belgium Lehert, P., Departement de Sciences Economiques Appliquees, Facultes Catholiques de Mons, 7000 Mons, Belgium Little, H., Psychology Department, University of Durham, Durham, UK Littleton, J., Pharmacology Group, Kings College, Manresa Road, London SW3 6LX, UK Lovinger, D.M., Department of Molecular Physiology and Biophysics and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA Moller, H.-J., Psychiatrische Klinik der Ludwig-Maximilians-Universitat, NuBbaumstr. 7,80336 Miinchen, Germany Paille, F., Centre d'Alcoologie, Hopital Fournier, 36 quai de la Bataille, 54035 Nancy Cedex, France Parot, P., Pharmaceutical Consultant, 12, avenue G. Pompidon, 92800 Puteaux, France Pelc, I., Laboratoire de Psychologie Medicale et d'A lcoologie, Universite Libre de Bruxelles (Campus Brugmann), Place Van Gehuchten 4, 1020 Brussels, Belgium Potgieter, A.S., Groupe LIPHA, 34 rue St-Romain, 69379 Lyon Cedex 8, France PreuB, U., Psychiatrische Klinik der Ludwig-Maximilians-Universitat, NuBbaumstr. 7, 80336 Miinchen, Germany Putzke, J., Max-Planck-Institut fur Psychiatrie, Klinisches Institut, Kraepelinstr. 2, 80804 Miinchen, Germany Quertemont, E., Laboratoire de Psychobiologie, Universite de Louvain, Place Croix-du-Sud, 1348 Louvain-Ia-Neuve, Belgium Siggins, G.R., Department of Neuropharmacology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA Soyka, M., Psychiatrische Klinik der Ludwig-Maximilians-Universitat, NuBbaumstr. 7, 80336 Miinchen, Germany Spanagel, R., Max-Planck-Institut Fiir Psychiatrie, Klinisches Institut, Kraepelinstr. 2., 80804 Miinchen, Germany Ufer, S., Psychiatrische Klinik der Ludwig-Maximilians-Universitat, NuBbaumstr. 7, 80336 Miinchen, Germany