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3.1 Dependence as an iatrogenic disease

There are dimensions to the risk of dependence that go beyond the effects of drugs on the body, and notably those relating to the question of the acceptability of risk. This is increasingly seen as a matter for patients; their expectations and perceptions of benefit and risk are central too. Naturally patients are very wary of dependence, but they are not unresponsive to notions of benefit and risk: the more convinced a patient was of the value of continuing treatment, the lower any risk might seem to be. For example, the belief that an antidepressant provided the serotonin that the body needs could be expected to powerfully reinforce psychic dependence on a drug, also to compound any risk of physical dependence by promoting long-term use. Thus the real risk of dependence might increase, though the patient might think it reduced. When someone believes in a drug and feels it working well, dependence problems do not seem to arise.

Another important factor in determining the risk of drug dependence is the commitment of those responsible to check well for evidence of problems, also to observe certain ground rules relating to openness and accountability. The significance of this is well illustrated in the benzodiazepine (BDZ) dependence saga - where the root problem was not about lack of data, but about the reluctance to seek out and reveal what there was. It was also about too many doctors not heeding patients, nor seeing much need to; lack of critical understanding; also perhaps too much of the conviction that meaning well means doing good. (Medawar, 1992, 1996). Some doctors were of course concerned, but the focus early on was not specifically about some risk of dependence; it was mainly about very high levels of prescribing (and repeats) and something of a diagnostic free-for-all.

" ‘Well, Mrs Smith, I have listened to your story and examined you, and it seems to me you are a case of diazepam. You had better have some anxiety’. It seems to me that whether or not our patients are hooked on the drugs, the doctors are certainly hooked on the diagnoses". (Marinker, 1972)

The main counter-argument to this comes close to the justification often given for prescribing antidepressants today. This was the explanation given 20 years for prescribing BDZs on such a scale (over twice levels of consumption today), and it had a decisive influence on national drug policy at the time:

"At first sight there appears to be a dramatic and disturbing increase in their use" (but) ... "If we take relatively recent figures there is probably a level of significant psychiatric morbidity in the population of some 20-30% of which about half is recognised by general practitioners".... (in addition), " ‘patients do not ordinarily accept psychotropic drug medication lightly.’ " (More evidence is needed but, on the best there is): "psychotropic drugs appear to be used conservatively by doctors (ie underused) rather than overused (and) their current consumption is not excessive relative to the level of emotional morbidity in the community." (Marks, 1978)

With hindsight, it is clear that the evidence of benzodiazepine dependence was there all the time, though not revealed and/or obscured: blindness, bias and self interest all played their part, and wishful thinking too. Given the widespread assumption (until the mid-1980s) that BDZs presented virtually no risk of dependence, doctors rather assumed that people took them for years because they really worked.

Doctors also tended to think that, if patients got distressed when they tried to stop taking their drugs, it was a sign of relapse and the emergence of underlying illness. This reinforced the assumption that the drugs really worked and led to more prescribing and increased dependence. Much the same thing had happened with other drugs prescribed for anxiety, insomnia and depression, on many occasions this century, and in one before. (Medawar, 1992)

The turning point in getting the BDZs recognised as drugs of dependence came in the early 1980s, just a year after the Committee on Review of Medicines (CRM) published the results of a "systematic review". This had no discernible effect on prescribing behaviour and was a rather sloppy piece of work, much influenced by a misconceived study by the former head of the UK subsidiary of Roche, the leading manufacturer of BDZs (Marks, 1978). The CRM joined him in concluding that the incidence of dependence on benzodiazepines was about "5 - 10 cases per million patient months", (Committee on Review of Medicines, 1980) a figure which soon proved out by miles.

The turning point came with the publication of two controlled studies (Tyrer et al., 1981; Peturrson & Lader, 1981) which demonstrated that quite a high proportion of long-term BDZ users could be expected to experience significant withdrawal symptoms when they tried to stop - enough to persuade many not to try. These studies were straightforward enough and presented quite modest evidence; it was still strong enough to prompt something of a retraction from Marks (1983), if not from the CRM.

Though it was not much emphasised at that time, both studies also demonstrated the critical point that many BDZ withdrawal symptoms positively mimicked the symptoms of the conditions for which they were usually prescribed. The most common symptoms of withdrawal were insomnia and extreme dysphoria (mainly anxiety, tension and depression). These were easily mistaken as evidence of a relapse, though some other symptoms (sensory changes and impaired perceptions of movement) did help to distinguish the true withdrawal syndrome from any underlying condition.

These two studies began the process of legitimisation of many thousands of previously overlooked complaints. It was a slow process, involving irresistible public outcry; (Rantzen, 1985; Lacey & Woodward, 1985) then litigation (from 1987) and finally some regulatory action. (CSM/MCA, 1988) By then it had become clear that many long-term BDZ users recognised the dependence problem well before most doctors, and only after years of official denial that such problems might exist. The error was great: in the early 1980s, official estimates suggested that dependence might affect only a few dozen people; soon after, it seemed that between about 250,000 - 500,000 people might be involved (DTB, 1985; Ashton, 1987; BMJ, 1991).

" ... if the popular press and more recently the legal profession had not taken up arms against the overprescription of tranquillisers, the issue of benzodiazepine dependence would still remain a medical curio only for the pages of medical journals. The media and lawyers have undoubtedly altered prescribing practices, mostly for the better". (Hallstrom, 1991)

This episode again reminded the medical establishment that dependence could be even more of a problem when withdrawal symptoms didn’t appear. It took 15 years even to speculate this might be so and another ten to begin to do something about it. The nub of it was explained in an aside cast by a pioneer in the field, at a Roche-sponsored seminar held in 1976. Dr Leo Hollister’s investigations into the dependence liability of the BDZs, in the early 1960s, had convinced him there would be "a flood of reports of withdrawal reactions" for diazepam (Valium) and chlordiazepoxide (Librium), yet the flood never came:

"The probable reason is that patients abort these reactions early on because they think their original symptoms are returning, and they get back on the drug. So we rarely see the full-blown picture." (Hollister, 1977)

To this extent, the measure of a drug dependence problem is not so much that some people experience withdrawal symptoms, but that many others continue with treatment to avoid them. With the BDZs, the focus was mainly on the problem of the thousands who experienced sometimes vicious symptoms on withdrawal - but the real problem was to do with the hundreds of thousands of people who habitually suppressed them. Many still do.


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