Abstract
This year is the 50th anniversary of the birth of psychopharmacology, taken from the date of the first use of chlorpromazine in a psychiatric clinical setting. As a direct consequence, psychiatry has been completely transformed. The oral history recorded by David Healy from discussions with psychopharmacologists in his first two volumes is essential reading for anyone who wants to understand how psychiatry has reached our present predicament. But at the commencement of my review, I thought that three volumes sounded a bit excessive.
It probably would have been were it not for the fact that in this monograph Healy does a terrific job combining irreplaceable historical recollections with discussion and debate concerning difficult issues we face today. He sets the scene in the preface which is mostly an account of what has become his crusade against Prozac. Healy cites evidence that fluoxetine is associated with suicide by inducing akathisia in a proportion of patients taking the drug. There is no attempt at any even-handedness as he passionately dismisses negative findings and quotes from problematic documents which Eli Lilly has been forced to reveal in the courts. He particularly attacks an analysis he accuses of being selective, published by Lilly psychiatrists in the British Medical Journal in 1991 [1].
This particular issue highlights the current ascendancy of the pharmaceutical industry in drug development and testing, usually to satisfy regulatory requirements. The clinicians involved in study design and analysis are now usually employed by the companies who then publish their own findings. Independent clinicians are engaged as ‘contract researchers’ but are otherwise excluded and negative studies often do not see the light of day.
Healy and many of his interviewees point strongly to the vital contributions made by industry. After all with chlorpromazine it was Rhone-Poulenc which made the compound RP4560 available to Henri Laborit for use in his research on the mechanism of surgical shock. The coming together of psychopharmacologists and the pharmaceutical industry over the last 50 years has resulted in an enormous benefit for our patients, and Healy describes many company people performing heroic feats in drug development. But companies working in the field of prescription drugs have to balance profit motive and share price with ethical principles and collaboration with clinicians. Despite recent moves by industry to direct consumer communication, the patient-doctor relationship remains the cornerstone of medicine.
For me the highlights of the book were the historical accounts. The first interview is a discussion with seven clinicians who first used chlorpromazine in Lyon at the same time as Delay and Deniker in Paris. The first psychopharmacologists were all psychoanalysts, and one of their key findings was that Largactil improved psychotherapy with psychotic patients. Most significantly, they identified that the effective dose of Largactil needed to exceed 300 mg, and at these doses dyskinesias similar to those described in von Economo's encephalitis were also observed. Largactil enabled the discharge of many patients from hospital, and forced a change in community attitudes which hitherto held both patients and psychiatrists in dread and contempt.
The Lyonnese group had mixed feelings about Professor Jean Delay who was Deniker's boss. Although it was Deniker who observed the effect of Largactil, Delay was the first author on their paper. But different interpretations then emerge as Healy uses the technique of interviewing multiple witnesses of the same events. The last chapter features Jean Thullier who was looking after the open ward next to Deniker's closed unit in Delay's service. Deniker is unequivocally, but not entirely persuasively, credited by Thullier with the discovery of chlorpromazine as an antipsychotic. The Lyonnese mention that Hamon and colleagues in Laborit's military hospital, and a mysterious Mme Deschamps (a female psychiatrist – most unusual at the time) published first.
Why no one got a Nobel prize for various discoveries is a fascinating theme running through the book. Thullier hints that Delay was the villain. He sat on a Nobel committee and was aware his contribution to Largactil was insufficient. While Laborit and Deniker were honoured with a Lasker prize they missed the Nobel, as did Kuhn (who discovered the antidepressant effects of imipramine) who was not regarded as a person of sufficient substance by Delay.
Other fascinating interviews include scientists who discovered various receptors (particularly Solomon Snyder), Joseph Schildkraut (who developed the catecholamine hypothesis of depression), Samuel Guze (who, with colleagues at the Washington University, came up with operational criteria for diagnosis) and Robert Spitzer (who developed the DSM-III). Judith Rapaport and David Sheehan are also interviewed, neither exactly historical, as are a number of others in the same category. Here, oral history becomes much more a discussion of current issues. Sheehan laments the demonization of benzodiazepines in the context of his work with Upjohn on alprazolam in panic disorder, while Ian Oswald talks of his litigation with the same company over triazolam.
Healy shows personal development over the three volumes. His questions and comments are far more informed and opinionated than in volumes 1 and 2, which adds interest significantly. This book is breathtakingly informative at times, often controversial and entertaining, and only occasionally boring or irrelevant. There are spelling errors – this suggests little editing but lends authenticity to interviews. There is a great deal to learn about psychopharmacology and psychiatry from the experiences and views of those contributing to this book.