Architects of the great depression

May 30, 1997

Rather than responding to the rise of mental disorders pharmaceutical companies have nurtured demand for their drugs and affected scientific progress, argues David Healy

In the past five years the antidepressant Prozac has rarely been out of the headlines. Depression is supposedly a serious illness; there are estimates that up to 100 million people in the world are affected. It is a sizeable market, but despite the fact that Prozac is portrayed as having been rationally engineered, as something of a magic bullet, no one claims it will slash levels of depression in the way that antibiotics wiped out disorders such as diphtheria. Why not?

In the late 1950s the newly discovered psychotropic drugs went from first human trial to license for general use within two months. The first antidepressant, imipramine, took almost two years. Why? Largely because drug companies believed that depression was rare. Sales of imipramine remained flat for years, until amitriptyline joined it on the antidepressant market. This was important, because, as well as selling amitriptyline as an antidepressant, the drug company Merck also bought and distributed 50,000 copies of a book called Recognising and Treating the Depressed Patient, by Frank Ayd. Whichever way one looks at this book, it facilitated the emergence of depression as an idea onto the medical agenda.

Even so, the antidepressant market remained small compared with the market for tranquillisers. It was not that clinicians did not recognise nervous problems in the community in the 1960s, more that they felt that such conditions were related to anxiety rather than to depression. The minor tranquilliser market boomed until the problems of dependency on benzodiazepines, drugs such as Valium, came to the fore in the late 1970s, along with critiques of the "tranquillisation of misery". It was then that the pharmaceutical industry took depression on board.

A series of epidemiological studies in the 1960s suggested the possibility of construing many nervous conditions as depressive. The realisation impacted on the development of a group of antidepressant drugs known as Selective Serotonin Reuptake Inhibitors - a group which includes Prozac - which appeared to have anti-nervousness properties. But it was only with the collapse of the minor tranquilliser market that the development of the SSRIs as antidepressants really went ahead.

At the same time came drug company support for campaigns by psychiatric associations to "Defeat Depression"; campaigns which helped legitimise drug companies' efforts to educate doctors to recognise depressed patients and treat them accordingly. The emergence of Prozac and related drugs had less to do with a process of rational bioengineering, now enshrined in popular mythology, and as much to do with the rationality of business processes.

There were linked developments in the late 1970's. With the classification of mental disorders in upheaval, the notion of anxiety neurosis was replaced with a range of "disease entities" such as Panic Disorder, Obsessive Compulsive Disorder (OCD) and Social Phobia - providing a number of marketing opportunities. Companies seeking to market new compounds publicised these new concepts as disorders that their medicines could treat.

Panic Disorder was first described in 1964. By 1980 it was still almost unheard of. Yet by the mid-1980s it was one of the most easily recognised psychiatric terms and one of the commonest diagnoses. Again a company, this time Upjohn, supported a wide range of studies worldwide, focusing on panic disorder. It would be reasonable to expect that increasing recognition of the disorder would lead to increased sales of a relevant drug treatment. And indeed both the recognition of panic disorder and sales of Upjohn's drug alprazolam increased dramatically through the 1980's.

Since then other companies have followed suit. In an effort to sell clomipramine Ciba-Geigy has publicised Obsessive Compulsive Disorder. As recently as 1980 there were estimates that fewer than 0.01 per cent of the community suffered from OCD. Today estimates of its frequency run at 2 to 3 per cent of the community - over one million people in the United Kingdom. Drug companies have not created OCD where it did not exist but they have helped market evidence of its frequency and helped make clinicians more likely to recognise it.

This can be done by sponsoring educational meetings, scientific symposia or journal supplements, and by supporting patient groups who in turn agitate for resources to manage their condition. In a similar manner companies are helping raise the profile of Social Phobia, a condition that was all but unrecognised until the early 1990s.

In stark contrast, companies have been reluctant to market SSRIs as treatment for premature ejaculation, despite a lot of evidence that drugs active on the serotonin system can ameliorate sexual dysfunctions and even though as many as one third of men are premature ejaculators. Company avoidance here owes something to concerns about involvement in areas that might compromise sales of other compounds.

Commercial interest does not only affect the delivery of drugs, it can affect the evolution of science. In addition to their therapeutic functions, psychotropic drugs can be used to explore how memory and other cognitive functions work. At present, however, there is little research in this area. There was far more during the 1950s and 1960s. Such studies require time and money. They could be undertaken as part of the development programme of new drugs along with the (currently compulsory) studies to look at the effect of these agents on cardiac or respiratory functions, but this is not happening. Yet new branches of science - pharmacoepidemiology and pharmacoeconomics - have come into existence recently partly by virtue of support from the pharmaceutical industry. The difference between pharmacoepidemiology and pharmacoeconomics on the one hand and pharmacopsychology on the other is that the former yield data which can be used to enlarge markets whereas the latter is more likely to yield data revealing which individuals might/might not benefit from particular treatments. This is likely to restrict market size for individual drugs.

In my opinion the notion that companies market certain evidence and effectively inhibit the dissemination of other evidence suggests that the market in mental health is rather like other markets as described by J. K. Galbraith in The New Industrial State. Galbraith argues that corporations do not simply respond to pressures from the marketplace but actively intervene to create a marketplace to suit their needs.

In mental health, the question of whose interests key concepts serve is not one that is only relevant to pharmaceutical corporations and the market in drug therapies. Psychotherapists engage in something similar.

Only ten years ago the dissociative experiences that are now seen as a hallmark of post-traumatic stress disorder and are "expected" in cases of abuse occurred only rarely in victims of abuse. Coached by TV programmes, movies and the writings of psychotherapists, patients now appear to have a profusion of dissociative symptoms - all the way up to the extreme of multiple personality disorder. Psychotherapists tend to coach patients in the nuances of politically acceptable clinical presentations.

Will evidence-based medicine sort out these problems? Almost certainly not. Evidence-based medicine is more likely to lock the problems in place; increasingly only those who can produce the evidence will be able to play the game. Appeals to evidence-based-medicine risk handing power to those who have the means to produce evidence by means of the only method currently sanctioned - randomised control trials.

Few groups can afford to do this. Those which can have an interest in the outcomes. The trials may be independent, their conduct perfect, but if only certain questions are addressed, the field as a whole is affected - or will be once the resulting evidence is marketed. The situation calls for a paraphrase of George Bernard Shaw to the effect that every profession is a conspiracy against the public.

David Healy is reader in psychological medicine and director of the North Wales Department of Psychological Medicine, Bangor. His book The Antidepressant Era is to be published by Harvard University Press.

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