It has been said that scientific progress is made by standing on the shoulders of giants. David Healy must have had a fascinating adventure interviewing the giants that forged psychopharmacology. This is the third volume of his interviews, which have included over 78 contributors, all great or well-known names such as Axelrod and Carlsson (Volume I), Janssen and Schou (Volume II), and Schildkraut, Snyder and Sulser in the present volume.
But did some giants have feet of clay? How is it that the pharmaceutical industry has come to dominate the field? Healy points out that drug companies “ are now not simply confined to finding drugs for diseases. They have the power to all but find diseases to suit the drugs they have.” Pierre Simon (Sanofi Pharmaceuticals) remarks: “In the beginning the pharmaceuticals industry was run by chemists. This was not so bad… Now most of them are run by people with MBAs… people who could be the chief executive of Renault, Volvo or anything. They don't know anything about drugs”. The problem comes when a chemist presents an interesting drug to the financial analyst, who asks: “What is the market?” The chemist has to decide for what indication the drug will be developed. If the indication is not there, it must be created.
One of many examples of this process was the development in the 1970s of alprazolam (Xanax) for panic disorder. According to David Sheehan (Institute for Research and Psychiatry, Tampa, Florida), the marketing of this drug involved a “clear strategy” to take advantage of the medical profession's confusion in the classification of anxiety disorders; “to create a perception that the drug had special and unique properties that would help it capture market share and displace diazepam from the top position… There was in fact nothing unique in this regard about Xanax… benzodiazepines were all good for panic disorder”. Xanax was marketed by Upjohn with Food and Drug Administration approval of doses up to 6 mg daily (equivalent to 60-120 mg diazepam). It is perhaps no coincidence, as Healy observes, that the effective incidence of panic disorders has grown a thousand-fold since 1980.
Sheehan relates a similar ‘deliberate tactic’ used to market 5-HT1A agonists by generating hysteria in the medical profession about the dangers of benzodiazepines. The 5-HT1A agonists were not a great success, but were succeeded by the selective serotonin reuptake inhibitors (SSRIs), which seemed to show activity in a range of anxiety disorders. Interestingly, according to Healy, the effective incidence of depression, obsessive—compulsive disorder, social phobia, and post-traumatic stress disorder has also increased a thousand-fold since 1980. There are now a number of ‘me too’ SSRIs because they are cheaper to make than new drugs. Fridolin Sulser of Vanderbilt University notes: “ If you can get 20% of fluoxetine's market, you can make 400-500 million dollars a year with very little investment in research and development”. He adds, sadly: “I don't know how to solve this dilemma in an industrial society that is so heavily driven by profits.”
Other sinister tales about the machinations of drug companies abound. Ian Oswald describes his well-known battle to get his paper about Upjohn's drug triazolam (Halcion) published, only to find that the then editor of Archives of General Psychiatry was funded by Upjohn and had sent the paper to Upjohn to referee. Pierre Simon relates that reports of adverse effects of sulpiride were censored by the French drug company Delagrange. Raymond Battegay, former professor at the Basel Department of Psychiatry, tells of withdrawal of support by Roche of a study comparing moclobemide with cognitive—behavioural psychotherapy: “apparently they feared that psychotherapy would have the same effect as the drug”.
And yet, this book is not a diatribe against the pharmaceutical industry. It must be admitted that extensive clinical trials are too expensive to carry out without drug company support. We all depend on the industry to bring money into academia. A study of a drug that reduces platelet aggregation involved 500 researchers and 20 000 patients tested for 3 years. It cost Sanofi around $250 million. No academic or clinical department can compete with Sanofi's budget for research, which, Simon remarks, is larger than that of the whole French INSERM. Although drug companies pay little attention to brain mechanisms, and theory is secondary to the development of drugs, it must also be admitted that much scientific progress has resulted from the use of drugs such as chlorpromazine, imipramine, benzodiazepines and fluoxetine.
Thus, it seems that money, not science, drives pharmacology. What can the medical profession do? A word of advice about training is given by Solomon Snyder of Johns Hopkins University, Maryland: “It is important… to come up with new ideas. PhDs are very well trained to be so critical that they criticise their own thoughts, so they're never creative… People without such fancy training… don't know about that and just try to think new thoughts. My own psychology is if somebody said day is day, I might say maybe day is night, and that attitude always helps”. Further advice from other contributors is to stick close to the bedside: it is salutary to note that the novel effects of chlorpromazine and of imipramine were first observed by nurses. The discovery of these and many other drugs was serendipitous of which Simon offers a definition: “A young man looking for a pin in a haystack finds the farmer's daughter… if the guy is not interested in the farmer's daughter, he has no chance of doing anything”. Perhaps the message is that academic psychopharmacologists should search for the farmer's daughter instead of the pin, but get the drug companies to pay for her dowry.
Readers of this book are advised to peruse it piecemeal. To enjoy a stroll in the company of giants, it is best to walk with them one at a time. Those who do so will find many thought-provoking ideas and may begin to question the widespread assumption that there is a drug treatment for every psychiatric illness, whether already recognised or yet to be described. As Professor Battegay disarmingly remarks to his interviewer: “I don't know, Dr. Healy, if psychiatry is really necessary…”.
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