SLIDES: Re 'dependence' on barbiturates, benzodiazepines and antidepressants

"Addiction to the barbiturates, in the strict sense of the word, probably does not occur. Habituation, in contrast, is not infrequent and certain patients may experience craving and psychic disturbances after the barbiturate is withdrawn. This phenomenon is, however, rather characteristic of the sedative-hypnotic group of drugs ..." (L. Goodman, A. Gilman, The Pharmacological Basis of Therapeutics, [New York: Macmillan, 1941], 135.)

"Following an extensive review of all available data the committee concluded that, on the present available evidence, the true addiction potential of the benzodiazepines was low. The number dependent on the benzodiazepines in the UK from 1960 to 1977 has been estimated to be 28 persons. This is equivalent to a dependence rate of 5 -10 cases per million patient months" (Committee on Review of Medicines, Systematic Review of the Benzodiazepines, Brit Med J, 29 March 1980, 910-912).

"Benzodiazepine dependence would be of minor clinical significance if it occurred only in those few individuals taking high doses of drugs; but it would be very important indeed if it supervened even to a minor degree in patients on usual clinical doses. Our clinical impression is that many patients experience symptoms on reduction or withdrawal of their benzodiazepine medication, and that whilst these symptoms somewhat resemble those of anxiety they differ qualitatively and are often more severe than those for which the medication was originally given" (C. Hallstrom, M. Lader, Benzodiazepine withdrawal phenomena, Int. Pharmacopsychiat, 1981, 16, 235-244).

"Dependence on the benzodiazepines does occur. Patients taking these drugs, even at therapeutic doses, for two or more months, may develop a physical withdrawal syndrome. The cardinal feature of the syndrome is anxiety, which may be mistakenly interpreted as a recrudescence of the original anxiety for which the drug was prescribed" (N. Hockings, B.R. Ballinger, Hypnotics and anxiolytics, in New Drugs, [London: British Medical Association, 1983), 149-155.)

"The medical profession took nearly 20 years from the introduction of benzodiazepines to recognise officially that these minor tranquillisers and hypnotics were potentially addictive. The 'happiness pills', which had been propping up a fair proportion of the adult population since the early 1960s, were found to have an unexpectedly bitter aftertaste: doctors and patients alike were unprepared for the problems of dependence and withdrawal that are now known to be common even with normal therapeutic doses" (Editorial (Anon), The benzodiazepine bind, The Lancet, 22 September 1984, 706)

"The extent of pharmacological dependence with regular as opposed to intermittent dosage of benzodiazepines was not fully appreciated until recently. This was probably because prominent features of drug dependence, such as tolerance and escalation of dosage, are uncommon among patients starting on normal doses. The chief manifestation is a withdrawal syndrome on stopping the drug" Anon (A. Herxheimer, ed.), Some problems with benzodiazepines, Drug & Ther Bull, March 25 1985, 23 (6), 21-23

"In the UK, 11.2% of all adults take an anti-anxiety drug at some time during any one year. But over a quarter of these people (3.1% of all adults) are chronic users, taking such medication every day. Even at a conservative estimate, 20% of these will develop symptoms when they attempt to withdraw. That means a quarter of a million people in the UK. The sooner the medical profession faces up to its responsibilities towards these iatrogenic addicts, the sooner it will regain the confidence of the anxious members of our community" (M.H. Lader, A.C. Higgitt, Management of benzodiazepine dependence - Update 1986, Brit J Addiction, 1986, 81, 7-10)

"There is now little doubt that regular use of benzodiazepines can lead to drug dependence in patients who are not drug abusers. Such patients come to rely on the drugs for psychological comfort and suffer withdrawal symptoms if the drug is stopped or the dosage reduced. It is estimated that one-third of patients taking benzodiazepines for six months become dependent … Present estimates suggest that perhaps 500,000 people in the UK … are now dependent on benzodiazepines" (H. Ashton, Dangers and medico-legal aspects of benzodiaz-epines, J. Med Defence Union, Summer 1987, 6-8).

"It seems likely that many popular beliefs about benzodiazepine 'addiction' are related to the clear cut and increasingly documented phenomenon of withdrawal reactions following the use of these drugs and to the resulting difficulty anxious patients sometimes have stopping drug treatment because of such reactions. This phenomenon (ie inability to discontinue the drug because of withdrawal symptoms) is termed ' dependence' and by itself is enough to qualify patients for the new DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised) diagnosis of 'psychoactive substance dependence" (P.R. Roy-Byrne, D. Homer, Benzodiazepine withdrawal: overview and implications for the treatment of anxiety, Am J Med, June 1988, 84, 1041 - 1052).

"It has been estimated that one in three patients prescribed benzodiazepines in normal therapeutic doses for six weeks would experience withdrawal symptoms if treatment were withdrawn abruptly. Even with gradual withdrawal, patients would request further prescriptions. Thus, there is a considerable risk of dependence even in comparatively short-term use" (M.A. Cormack, R.G. Owens, M.E. Dewey, The effect of minimal interventions by general practitioners on long-term benzodiazepines use, J Roy Coll Gen Practitioners, October 1989, 39, 408-411).

"The presence of a predictable abstinence syndrome following abrupt discontinuance of benzodiazepines is evidence of the development of physiological dependence … "Historically, long-term, high-dose, physiological dependence has been called addiction, a term that implies recreational use. In recent years, however, it has become apparent that physiological adaptation develops and discontinuance symptoms can appear after regular daily therapeutic dose administration ... in some cases after a few days or weeks of administration. Since therapeutic prescribing is clearly not recreational abuse, the term dependence is preferred to addiction, and the abstinence syndrome is called a discontinuance syndrome" (American Psychiatric Association Task Force on Benzodiazepine Dependency. Benzodiazepine Dependence, Toxicity, and Abuse. Washington DC: APA, 1990.)


"The withdrawal syndrome complicates the evaluation of patients after drug discontinuation since both patients and physicians often interpret the onset of symptoms as an upsurge of 'anxiety' related to incipient relapse, and resume treatment with the gratifying subsidence of the 'anxiety'. This may cause both patients and physicians to overvalue the importance of the medication to the patient's stability" (J.C. Kramer, D.F. Klein, M. Fink, Withdrawal symptoms following discontinuation of imipramine therapy, Am. J Psychiatry, 1961, 118, 549-550).

"The patient clearly should be given as much information and help as possible in deciding whether to continue. Advice should include the facts that antidepressants are not habit forming or addictive and that a minimum of four months treatment is advised for classic depression to prevent relapse. This will enable the patient better to make an informed choice about continuation with treatment" (E.S. Paykel, R. G. Priest, on behalf of conference participants, Recognition and management of depression in general practice: consensus statement, Brit Med J, 14 November, 1992, 1198-1102)

"The incidence of significant symptomatology following antidepressant withdrawal is surprisingly high. Prospective studies have not been done, but retrospective surveys indicate that gastrointestinal and somatic distress develop in 21% to 55% of adult patients following discontinuation of imipramine … In summary, with careful observation antidepressant withdrawal symptomatology is frequently noted." (S.C. Dilsaver, J.F. Greden, Antidepressant withdrawal phenomena, Biological Psychiatry, 1984, 19 (2), 237 - 256.

"The withdrawal of antidepressants can produce changes in mood, appetite and sleep that are apt to be incorrectly misinterpreted as indicating a depressive relapse ... The probability of depressive relapse is low in the days and weeks after the discontinuation of antidepressants, and the cumulative probability of relapse increases as a function of time when the patient is medication free ... In contrast the frequency of antidepressant withdrawal symptoms is high in the first 2 to 14 days following the last dose." S. C. Dilsaver, Antidepressant withdrawal syndromes: phenomenology and patho-physiology, Acta Psychiatr Scand, 1989, 79, 113-117.

"Fifty psychiatrists (50%) and 53 GPs (53%) responded to the questionnaire. Of the respondents, 36 (72%) of the psychiatrists and 16 (30%) of the GPs were aware that patients may experience antidepressant discontinuation events … and 10 (20%) psychiatrists and 9 GPs (17%) said they always caution patients about the possibility of discontinuation events. Conclusion: According to the results of this survey, a sizeable minority of physicians denied being confidently aware of the existence of antidepressant withdrawal symptoms. Education about discontinuation reactions, including the hallmark features, symptoms and course, is needed for both psychiatrists and family practice physicians" (A.H. Young, A. Currie, Physicians' knowledge of antidepressant withdrawal effects: a survey, J Clin Psychiatry, 1997, 58 (suppl 7), 28-30)

"You suggest that SSRI antidepressants have been shown to produce dependence and that the risk of their doing so is 'at least as great as with benzodiazepines'. I do not accept this. You are confusing dependence with a withdrawal state … the presence of a withdrawal state is neither necessary nor sufficient for a diagnosis of dependence." (R.E. Kendell, President, Royal College of Psychiatrists, personal communication, 28 November 1997)

"With respect to your contention that SSRIs can cause physical dependence, I am advised that evidence to date does not appear to establish such an effect" (F. Dobson, Secretary of State for Health, personal communication, 9 March 1998).