The trials and tribulations of antidepressant drugs.
Medicines Out of Control: Antidepressants and the Conspiracy of Goodwill
By Charles Medawar & Anita Hardon
In 1994, as lawyers for the pharmaceutical giant Eli Lilly were beginning a historic legal defence of the antidepressant Prozac, researchers were descending from all over the world on Miami Beach, Florida, for the twenty-fourth annual meeting of the American Society for Neuroscience. Among the 10,000 posters on show at the meeting, hundreds displayed research on the serotonin system, with scores of these devoted to fluoxetine hydrochloride, better known as Prozac. One poster showed the work of Ray Fuller of Eli Lilly, who invented Prozac. But Fuller wasn't there. He was in Louisville, Kentucky, giving evidence in the Eli Lilly Prozac trial. It involved a man called Joseph Wesbecker, accused of shooting 20 people in his workplace with an AK47 after being on Prozac for just over a month. Eight of his victims died and he committed suicide.
This was the mid-point of the Decade of the Brain. To attend the annual neurosciences meeting was to submit oneself to a tidal wave of varied research programmes, from genetics to neuronal degeneration, from memory to neurotransmitters, from pharmacology to the visual cortex, and from brain imaging to new pain therapies. Nowhere in the world was there such a large and optimistic gathering of scientists convinced that they were about the change the world.
The decision of the House and Senate of the United States to designate the 1990s as the Decade of the Brain was not just scientific optimism, however; it was the result of lobbying by the pharmaceutical industry. The carrot had been budgetary: an estimate that some $350 billion was being lost to the US economy each year through brain-related ills, including depression, Alzheimer's and the consequences of aggressive behaviour. The promise of major social and medical amelioration was driving and directing the rapid expansion of investment and funding. These two volumes, Medicines Out of Control and Let Them Eat Prozac, measure the failure of the Decade of the Brain to deliver the goods in the crucial arena of new antidepressants.
A chief benefit of new psychopharmacology was the hope that designer medications would bring an end to dependence problems. In theory, matching a chemical product to known receptor sites would avoid the unwanted side-effects of older drugs, whose discovery was mainly serendipitous. Medicines Out of Control tells the story of a looming crisis in the side-effect of dependency on new drugs. The turning point signalled by the authors was 25 June 2003, when GlaxoSmithKline published an amendment to the prescribing instructions for the antidepressant Seroxat (Paxil). The company revised its earlier estimate of the risk of withdrawal reactions from 0.2% to 25%. In setting the scene for their thesis, the authors tell us that the prodigious increase revealed that “science was catching up with common sense”.
One of the central issues of the book is the mismatch between the industry's clinical-trial systems and the anecdotal evidence of patients. The authors argue that evidence from users began to flow in earnest in the mid-1990s with the growth of the Internet. The web “had begun to change history” as users of antidepressants began to compare notes and exchange ideas on an unprecedented scale. The authors' conclusion — that the community created by new information technology should be adapted and adopted by the medical profession, especially in the case of drugs for the mind — seems not only sensible but obvious. Will the pharmaceutical industry respond? Is it in their interest to do so?
Let Them Eat Prozac: The Unhealthy Relationship between the Pharmaceutical Industry and Depression
By David Healy
Which brings us to David Healy's Let Them Eat Prozac, an even more sombre story of psychopharmaceutical folk and patients. For beyond the dangers of dependence are the alleged dangers of aggression and self-harm, particularly in the case of the selective serotonin reuptake inhibitors (SSRIs), of which the most famous is Prozac. Healy, who is a psychiatrist and prolific author of books and articles on psychopharmacology, used to prescribe Prozac happily. Like many clinicians, he was impressed: just one pill a day to bring a patient out of a wide variety of depressive complaints. Only with time did he realize that his patients were complaining of agitation and suicidal ideation. Then came that landmark trial in Louisville involving Wesbecker and Eli Lilly. The many expert witnesses revealed the alarming relationship between new brain science and the commercial goals and shortcuts of the pharmaceutical industry.
Healy's tale is complex and detailed, bringing together a huge amount of clinical-trial data and case histories. Ultimately, the book is about science, society and the power and misuse of commercial promotion. “We are facing a future of real biomedical developments,” he concedes, but these are taking place in a world “in which corporate capacities to colonize the consciousness of citizens, physicians, regulators, and others outstrip their capacities to bring real benefits on stream”. His investigation is impressive but is, in the final analysis, depressing, for he has no ready answers for the ills he describes. One can only hope that the benefits of commercially based psychopharmacology ultimately outstrip the catastrophes — but Healy is not prepared to concede such a conclusion. Perhaps our best hope is for vigilant and painstaking whistle-blowers, of which the authors of these two studies are formidable examples.