The Benzodiazepines: Use, overuse, misuse, abuse PDF
Preview The Benzodiazepines: Use, overuse, misuse, abuse
The Benzodiozepines The Benzodiazepines Use overuse misuse abuse By John Marks, MA, MD, FRCP, FRCPath, MRCPsych Fellow and Director of Medical Studes Girton College Cambridge MTP Published by MTP Press Limited St Leonard's House Lancaster, England Copyright © 1978John Marks softcover reprint of the hardcover 1st edition 1978 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission from the publishers. lSBN-13: 978-94-011-6205-0 e-lSBN-13: 978-94-011-6203-6 DOl: 10.1 007/978-94-011-6203-6 Redwood Burn Limited, Trowbridge & Esher Contents Summary 1 Glossary 3 Part I The general problem of dependence 1 Introduction 7 2 A broader concept of 'psychotropics' 9 3 Types of drug dependence 13 Part II Benzodiazepine dependence 4 Animal studies 19 5 Dependence liability of benzodiazepines in humans 23 Human experiments 23 Ex cathedra statements 26 Critical analysis of published reports 29 Large-scale surveys 33 6 Clinical description of benzodiazepine dependence 35 7 The status of benzodiazepines in the realm of mixed drug abuse' 39 8 The level of benzodiazepine dependence risk in humans 41 v Contents continued Part III Significance of benzodiazepine dependence within the community 9 Introduction 49 10 The level of use 51 11 Medical aspects 59 Medical care not cure 59 Intrinsic safety 59 Comparison of drugs with other forms of therapy 63 Reducing the dependence risk 64 12 Social aspects 67 Social approach to mental illness 67 Psychotropic drugs - an incontestable necessity 68 Education towards rational use 69 13 Legal aspects 71 VI Contents continued Port IV Conclusions 14 Summary of conclusions 79 The benzodiazepines 80 Appendix A 81 Appendix B 93 Appendix C 95 References 101 Index 109 vii Foreword The story of the benzodiazepines is a fascinating one: the synthesis of a long series of inert compounds and the abandonment of the project: months later, the renewal of the project and the discovery that this compound R05-0690 (Librium ®) was a sedative and muscle relaxant in laboratory animals: the recognition that its postulated structure was wrong and that it was in fact a member of an entirely new chemical class: the excitement caused by the discovery of the powerful taming effect of the drug in wild animals: the even greater excitement in medical circles when its dramatic anxiety relieving effects were cstablished in humans: the subsequent enormous world wide usc of drugs of the benzodiazepine group. I have reason to know the story well for during that period I worked in various capacities in research, marketing and manage ment in the British subsidiary of F. Hoffmann-Ia Roche. It was during this period that I became interested in whether dependence on benzodiazepines could occur and if so to what extent, but felt that this could be examined best from outside the concern. Having now retired from Roche back to academic medicine I have taken the opportunity to examine and analyse the evidence. Although this has been an independent analysis, and I take full responsibility for any poor deductions or conclusions, I should like to express my thanks to Hoffmann-Ia Roche for the information sources they have made available to me that helped to find cases in obscure publications that I might otherwise have missed. I should particu larly like to thank John Ward on their staff who helped cross-check cases which had been published and also recorded in official records. But any errors of commission or omission are mine alone. Cambridge, JOHN MARKS February 1978 IX Summary I. Definitions are given for the terms drug, drug abuse, depen dence, tolerance, misuse and overuse. The general term 'addiction' is no longer recommended and 'dependence' is preferred, implying the interaction ofliving organism and drug which leads to its compulsive intake - pages 3 to 4. 2. There is a continuum of pleasure-giving non-productive activi ties on which humans may become 'dependent' to a gr.eater or lesser extent. These may be included within the general term 'psychotropics'. Some of these are socially acceptable, others not. Drugs are only one group of the psycho tropics - pages 9 to I I. 3. The total level of dependence on general 'psychotropics' appears to be relatively constant but fashion changes the pattern within this totality. Education to reduce total human dependence is a difficult and unrewarding task - pages 68 to 70. 4. Because there is a continuum of dependence the definition of a borderline unacceptable level involves a value judgement which depends inter alia on social, political and economic factors as much as medical considerations - pages 9 to IO. 5. Animal and human experiments demonstrate that dependence on all current sedatives and tranquillizers, including the benzo diazepines, can occur if large doses are given for prolonged periods-pages I9 to 26. 6. Dependence on benzodiazepines occurs rarely under conditions of clinical use and then usually only after prolonged adminis tration at above average dosage. Clinically it resembles that described as 'barbiturate' or 'alcohol-barbiturate' type - pages 32t0 37· SUMMARY 7. The dependence risk with benzodiazepines is \'ery low and is estimated to be approximately one case per 5 million patient months 'at risk' for all recorded cases and probably less than one case per 50 million months in therapeutic use-pages 4! to 45· 8. The benzodiazepines are occasionally abused within the 'drug scene' particularly as the sedative component of multiple drug abuse, but this probably represents their wide availability rather than a high preference rating- pages 39 to 40. 9. Legislation is only successful as a means of reducing any abuse if it has wide public support. This particularly applies to the control of drug abuse. Hence drug control legislation should be reserved for drugs with high dependence risk-pages 7I to 75. ro. The level of risk and the dangers to individuals and society are of such a low order with the benzodiazepines that no additional con trois are necessary - pages 73 to 74. 2 Glossary Abstinence ,l,yndrome The syndrome which occurs in drug-dependent people when the drug is withheld. I t usually involves both physical and psycho logical manifestations, the nature of which varies with the drug on which dependence exists. Addiction A term which is still widely used but which is variously ·under stood and defined by physicians, sociologists and lawyers. It should be discarded for scientific literature and replaced by the term dependence (q. v.) as defined by the World Health Organ ization. Drug Any substance which when taken into the living organism may modify one or more of its functions. Drug abuse Persistent or sporadic excessive drug use inconsistent with or unrelated to acceptable medical practice. Drug dependence A state, psychic and sometimes also physical, which results from the interaction between a li\'ing organism and a drug, which is characterized by behavioural and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects and some times to avoid the discomfort of its absence. Tolerance may be present. Alisuse Medical or lay use of a drug for a disease state not considered to be appropriate by the majority. 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