Before Prozac. The Troubled History of Mood Disorders in Psychiatry

This is an entertaining book, written as if Shorter had half an eye on a screenplay. The plot centres on the pharmaco-politics of the past century. The cast are dark institutions: the Food and Drug Administration (FDA; power-hungry); academic psychiatry (vain and untrustworthy); and the pharmaceutical industry (money-grubbing). Our heroes are the pharmacologists of the past, untroubled by the cruel whisper of the blinded trial.

Scene 1: Shorter has us imagine a desert, barren but for two tall cacti. One represents selective serotonin reuptake inhibitors (SSRIs), the other, atypical antipsychotics. We travel back in time to learn how we came to be in this desperate place…

Shorter believes that the pharmacotherapy of depression could have been a lot more exotic – and effective – than it is now. He suggests that political and commercial power games (and the unfortunate DSM catch-all construct `major depression’) have swept away useful treatments for depression: first opiates, amphetamines, alcohol and cocaine; followed by barbiturates, meprobamate and methylphenidate; and then monoamine oxidase inhibitors, tricyclics and benzodiazepines. Apparently, we are left today with the anaemic SSRIs.

Like any good history lesson, this one nails a recurrent theme: every time a psychiatric drug class gets the chop, it follows a political furore about addiction or lethality or both. Barbiturates – addictive and lethal; benzodiazepines – addictive; tricyclics – lethal, and so on. On cue, the SSRI cactus is being sawn down right now. In Scotland, for example, a wearisome target has been set by civil servants to reduce antidepressant prescription by 10% – such is the fact-free ministerial concern that general practitioners are handing them out like sweeties – despite consistent evidence that depression is under-recognised and under-treated wherever researchers take the trouble to look.

Shorter does not collar the real villain: that role is surely taken by the general public’s distaste for the very idea of psychopharmacology. As the `Defeat Depression’ campaign demonstrated, tabloid folklore would have antidepressants as some sort of highly addictive emotional anaesthetic. Stigma thus ensures that demonising psychiatric drugs has always been a sure-fire crowd-pleaser for the politician. Whether it is 1963, with US Senator Hubert Humphrey professing horror at the prescription of meprobamate `as freely as aspirin’, or today, as British MPs jostle to condemn antidepressant prescription volumes, the careerist rhetoric remains the same.

Anyone picking up Shorter’s book to enjoy a diatribe against the evil of antidepressants will be disappointed (NICE guidance is the place to go for that). His concerns lie with the paucity of effective drugs, not the principle of chemical treatment. But his assessment of the value of older therapies is not correct: opiates and alcohol are possibly not the best approach to mood disorder (though a fair proportion of the antidepressant-sceptical `public’ seem keen), whereas the serendipitously discovered antidepressants and their descendants were never wholly effective despite the advance they represented. The monoamine hypothesis that grew as drug mechanisms were unravelled could never be adequate either. Mundane commercial conservatism was responsible for the raft of `me-too’ agents that followed: industry simply got on with making products to sell. Academic psychiatry did not have the technology or the ideas to contribute anything new, and got on with making an increasingly fine-grained but futile map of the monoamine system. A sufficiently sophisticated neuroscience of mood disorder just does not exist to guide rational drug development. Possibly it is beginning to emerge now, from interplay between the realms of molecular biology, imaging and neuropsychology. But it may be too late, as it was for Charlton Heston, emerging dumbfounded from a crashed spacecraft to discover that his planet had been taken over by an advanced but brutish civilisation of cognitive therapists. (My memory of plot detail may be a little hazy here.)

The hyperbolic blurb on the back cover would have you believe that this book is a revelatory work of Kuhnian stature. It is not. But it is engaging, sprinkled with Chandleresque dialogue – FDA agents say things like, `Baby, it ain’t gonna happen’ and `your products are toast’ – and fun: you will learn that Leandro Panizzon (who synthesised methylphenidate) named his drug `Ritalin’ after his wife Rita because she liked to take it before tennis matches. And that a horse named Marsilid (after the first monoamine oxidase inhibitor used in depression) won in the 9th at Belmont in 1949 (perhaps it was cheating too).

I would recommend the book as solid summer holiday reading: but don’t just continuously develop professionally on the beach – bid for the film rights.

Ian Reid

University of Aberdeen, Cornhill Hospital, Aberdeen AB25 2ZH. Email: .(JavaScript must be enabled to view this email address)

By Edward Shorter. Oxford University Press. 2008. US$29.95 (hb). 320 pp. ISBN: 9780195368741