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3.5 Where the goalposts of dependence used to be

In 1990, the American Psychiatric Association published its Task Force report on Benzodiazepine Dependence, Toxicity and Abuse. On the definitions and criteria used in this report, the SSRIs and other antidepressants would certainly be classified as drugs of dependence: "The presence of a predictable abstinence syndrome following abrupt discontinuance of benzodiazepines is evidence of the development of physiological dependence". The goalpost have now moved but, in those days, the APA specifically recommended the term "dependence" to distinguish between what happened with the BDZs and the problems of ‘addiction’ and ‘abuse’:

"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." (APA, 1990)

The APA found very little evidence of dosage escalation: "some clinicians have, however, observed slight increases in benzodiazepine doses over time ... These dose increases are usually small, and long-term use does not lead to significant dosage increases over time or to high dose abuse". Neither was there said to be much evidence of ‘poop out’ or diminution of therapeutic effect, though "there may be mild tolerance to anxiety in some patients". Long term use of BDZs was identified as the major risk factor and "4-8 months seems to be the critical time period for the development of therapeutic dose dependence".

The Task Force concluded with advice about risk and benefit, emphasising that this always came down in the end to the individual patient’s needs "rather than on global and general formulations". That said, "the question of benefit outweighing risks ... becomes less clear when therapeutic doses are used over long periods of time", especially under any of the followings circumstances:

"Risks of chronic toxicity, especially cognitive impairment, true physiological dependence, and discontinuance symptoms are all more likely under the following conditions: 1) high dose, 2) daily dosing of more than four months duration, 3) advanced age, 4) current or prior history of sedative hypnotic and/or alcohol dependence including prior chronic benzodiazepine use, and 5) use of high potency, short half-life benzodiazepines. Alone or in combination, these risk factors raise serious questions about the wisdom of routine long-term use of benzodiazepines." (APA, 1990)

All this has now changed and perhaps the threat of mass benzodiazepine litigation lay behind it. The nub of it is this: for many years, "dependence" has meant either tolerance or withdrawal"; (DSM III, 1980) but "dependence" today literally means both tolerance and withdrawal, and at least one other symptom from the list below. (DSM-IV, 1994).

The great shift took place shortly after publication of the APA Task Force report on Benzodiazepines. The harbinger was the new formal definition of "dependence" in ICD-10, the WHO’s International Classification of Diseases, Part 10, on mental and behavioural disorders (1992). Then the American Psychiatric Association published the 4th edition of the Diagnostic & Statistical Manual (1994). See 2.5. The ICD-10 criteria "are close but not identical" to those in DSM-IV; both characterise dependence in non-therapeutic settings and in terms of frank abuse:

"A definite diagnosis of dependence should usually be made only if three or more of the following have been experienced or exhibited at some time during the previous year:

(a) a strong desire or sense of compulsion to take the substance;

(b) difficulties in controlling substance-taking behaviour in terms of its onset, termination or levels of use;

(c) a physiological withdrawal state ... when substance use has ceased or been reduced, as evidenced by the characteristic withdrawal syndrome for the substance; or use of the same (or a closely related substance) with the intention of relieving or avoided withdrawal symptoms

(d) evidence of tolerance, such that increased doses of the psychoactive substance are required in order to achieve effects originally produced by lower doses (clear examples of this are found in alcohol and opiate dependent individuals who may take daily dose sufficient to incapacitate or kill non-tolerant users);

(e) progressive neglect of alternative pleasures or interests because of psychoactive substance use, increased amount of time necessary to obtain or take the substance or to recover from its effects;

(f) persisting with substance use despite clear evidence of overtly harmful consequences, such as harm to the liver through excessive drinking, depressive mood states consequent to periods of heavy substance use, or drug related impairment of cognitive functions; efforts should be made to determine that the user was actually, or could be expected to be, aware of the nature and extent of the harm ..." (WHO, 1992)

 So great has been this change in definition that "benzodiazepine dependence" now hardly exists. By characterising "dependence" in terms of a conspicuously damaging inability to control drug use, the definition would exclude all but exceptional cases of dependence on BDZs. By directing doctors firmly away from any finding of dependence arising from usual treatment and practice, the new definitions contradict most of what the APA Task Force was saying less than a decade ago.

A more helpful definition might be one which started from concepts and principles acceptable to the public. Starting points might be that people should be told if treatment might involve any significant element of drug-induced drug consumption, and that "dependence" means, at heart, that some people will find it very hard to stop taking a drug when that is what they would really want to do.

Fundamental to the exclusion of both antidepressants and BDZs from the current definition of "substance dependence" is that someone continues to take a drug "despite significant substance-related problems" and notably "drug-seeking behaviour". Neither would normally apply to a patient with a secure supply of prescribed drugs, and certainly not when medical opinion is convinced of the value of long-term antidepressant use.

The dependence problem with BDZs was not about drug-seeking behaviour and people wanting to take drugs. The problem was that withdrawal symptoms frustrated many peoples’ attempts to stop when they wanted to, sometimes for years and in frightening ways. Thus, the new definitions leave open the possibility that another such problem might be happening now, but not recognised for what it is.

These definitions overlook such problems by their very design. They represent dependence as a clear-cut problem and an on-or-off state rather than as a "continuous variable",(Nutt, 1996) overlooking consistent evidence from the past that dependence is usually a very subtle complication, easily missed. Moreover, little or no account is taken of sometimes substantial differences in individual response, found with both antidepressants and BDZs. One of the lessons with BDZs was that, given similar drug exposures, different individuals had sometimes dramatically different responses - measured both in terms of levels of drug in the body, and experience on drug withdrawal. The fact that most users managed to quit without difficulty supported the widely-held view that it was really a problem to do with individual personality, if others felt truly hooked.

Bearing in mind that medicine is full of surprises, and that psychiatric medicine has had more than its fair share of the nasty ones, it would not seem safe to assume that antidepressants are in no sense drugs of dependence, or that it wouldn’t matter if they were.


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