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2.1 Do antidepressants work ?

Many people feel certain that antidepressants have helped them and may even have saved their lives. They might think it was na´ve or dangerous even to ask whether antidepressants work, and almost all health-care professionals would agree. By admitting the possibility they might not, the question flies in the face of seemingly rock-solid medical opinion and, whatever the answer, might promote loss of confidence in the effectiveness of treatment. This could add to the problems of depressed patients, put further demands on clinicians and health services and damage commercial interests and reputations.

But the reason for asking if antidepressants work is not to try to prove that they don’t; it is to review briefly the evidence that insists they do. Much of this evidence is based on carefully conducted clinical studies and trials, but what is actually being tested ? What is the "depression" these drugs treat ? What are "antidepressants" and what effects do they have ? What does "work" really mean, and how sound is the evidence they do ? The answer to the central question fundamentally depends on these and other matters of definition and interpretation.

The question "Do antidepressants work ?" also provides a framework for thinking about a range of underlying issues, including the relationships between nature & nurture, sickness & health and benefit & risk. Questions also arise about business conduct and the roles of money and influence; about organisational imperatives versus health goals; about the quality of science and the basis of trust; and about the effectiveness of law and regulation.

Similar questions were addressed in an earlier study (Medawar, 1992) which discussed the relationships between doctors, pharmaceutical companies, government and consumers - as reflected in the habitual prescribing of dependence-producing drugs for anxiety, insomnia, depression and related problems that go by a thousand other names. Over the past 200 years, doctors have prescribed an almost uninterrupted succession of "addictive" drugs, always in the belief they would not cause dependence or that patients would be mainly responsible if they did. In the beginning were alcohol and opium, then morphine, heroin, and cocaine; alongside were chloral; numerous bromides, barbiturates and related compounds, and then a score of benzodiazepine tranquillisers. In their day, all these drugs have been prescribed as sedatives for mental distress, and except for alcohol, also as weaning treatments for addiction to other drugs on the list.

The long-term efficacy of benzodiazepines proved largely an illusion, but only after more than 20 years of extensive use. The reason most people stayed on these drugs turned out to be they couldn’t readily stop taking them. They had become dependent on them, in rather the same way that people get dependent on alcohol: usually very subtly and sometimes to disastrous effect. It is a long, sad story and perhaps not over yet.

If history were to be repeating itself, it would be both because and in spite of authoritative denials that any risk is involved. If antidepressants were in some sense drugs of dependence, but not recognised as such, it would increase the element of risk and lead naturally to an over-estimation of their effectiveness as well.

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