Nature © Macmillan Publishers Ltd 1998

8

themselves in the original texts. Quite apartfrom his scientific skills, Cuvier was also aremarkable writer. Eager to convince, he hadan accurate, clear, elegant style and a greatsense of drama that allowed him to drawstriking and even sometimes dramatic por-traits of vanished worlds.

Throughout this book, Rudwick revealsthe interest that can be found in reading thetexts written by a man of science whose ideasand concepts deeply influenced nineteenthcentury society and who helped to raise theinternational status of anatomy and geologyas professions.Philippe Taquet is in the Laboratoire dePaléontologie, Muséum National d’HistoireNaturelle, 8, rue de Buffon, 75005, Paris, France.e-mail: taquet@mnhn.fr

Radical remediesThe Antidepressant Eraby David HealeyHarvard University Press: 1998. Pp. 317.$39.95, £19.98

Leslie Iversen

Over the past 50 years the discovery of drugsthat effectively treat the symptoms of schizo-phrenia, anxiety and depression has revolu-tionized treatment and led to radical changesin the way we view mental illnesses. DavidHealey’s book focuses on the discovery anddevelopment of antidepressants and pro-vides a fascinating insight into the history ofthis field. He skilfully interweaves hisaccount of the roles played by the key scien-tists and clinicians with the powerful influ-ence of pharmaceutical companies.

The first antidepressants were discov-ered, by accident, on each side of the Atlanticin the mid-1950s. The Swiss company CIBAtested imipramine in schizophrenia becausethe drug had been designed to resemble inchemical structure the first anti-schizo-phrenic agent, chlorpromazine. Althoughimipramine proved ineffective in the treat-ment of schizophrenia, an astute psychia-trist, Roland Kuhn, thought it had euphori-ant or stimulant effects in some of hispatients and he persuaded the reluctantcompany to test it in depression where itproved highly successful.

In the United States, meanwhile, anecdo-tal reports that the drug iproniazid hadeuphoriant effects in some of the tuberculo-sis patients for which it was developed werefollowed up by Nathan Kline, alreadyfamous for his work on reserpine in schizo-phrenia. Kline persuaded Roche to conducta trial in withdrawn depressed patientswhich proved highly successful. Kline, a skil-ful publicist, released the story to The NewYork Times and lobbied senior executives atRoche for continuing support. Althoughiproniazid and other monoamine oxidase

inhibitors (MAOI) quickly fell out of favourbecause of their associated cardiovascularhazards (the ‘wine-and-cheese’ effect), theyhad a major impact as the first effective anti-depressants in the United States. Kline wasinstrumental in lobbying Congress forfunds to support psychopharmacologyresearch and by the mid-1960s he hadappeared on the cover of Fortune magazineand had become one of the ten best knownmen in America.

The MAOI were soon followed byamitriptyline, developed by the Americancompany Merck and like imipraminebecause it chemically resembled chlor-promazine. The American psychiatristFrank Ayd, however, had heard about Kuhn’sresults with imipramine and persuadedMerck to do trials in depression, whichproved successful. Ayd also published aninfluential book on how to diagnose depres-sion in general psychiatric practice, whichhelped to make amitriptyline the first anti-depressant with major sales.

The drugs were expanding the diagnosticborders of depression, leading to the under-standing that depression was far commonerthan previously thought. This processreached its ultimate conclusion with Prozacand the concept that it could make some peo-ple feel “better than well”.

Healey has perceptive insights into therole of the pharmaceutical industry in thedevelopment of the psychopharmacologyera, and he portrays the often dramatic risesand falls in the fortunes of individual com-panies. He is at his best, though, in describ-ing the shenanigans let loose by the drug erain his own profession, psychiatry. The adventof effective drug treatments led to majorchanges in this branch of medicine — intro-ducing for the first time the concept of thecontrolled clinical trial and ‘evidence-basedmedicine’.

There were often intense clashes betweendifferent ideologies (defined by Healey as“distinguished by their judgement of whatought to be regardless of what actuallyexists”). The psychoanalysts who dominat-ed the profession in the 1950s and 1960swere pitted against the new biologicallydominated school who embraced the use ofthe new drugs and called for radical changesin the classification of mental disorders. Thetwo ideologies were often far apart — inmany US psychiatric hospitals the psy-chotherapists refused to be associated withprescribing drugs for their patients, leavingthis distasteful job to the “druggists”employed by hospitals. Eventually thereemerged a backlash against the drug era inthe form of “pharmacological Calvinism”— the belief that drug use is bad or evenpotentially dangerous if it makes you feelgood.

The rise of psychopharmacology as a newfield of research accompanied the drug era.

The “monoamine era” was heralded by theearly discovery that reserpine acted bydepleting monoamine neurotransmittersfrom the brain. This was followed by thefinding that monoamine oxidase inhibitorsand the tricylic antidepressants (imi-pramine and amitriptyline) acted by makingmonoamines more available in the brain (byblocking the degrading enzyme or the tissuereuptake processes respectively). In the1960s and 1970s the ‘noradrenaline hypoth-esis’ of depression dominated, althoughextensive attempts to provide evidence forthe underactivity of brain noradrenalinesystems predicted by this hypothesis indepressed patients all failed. Nevertheless,the hypothesis seemed to gain support fromthe discovery that new drugs that targetednoradrenaline reuptake (desipramine andmaprotiline) proved clinically effective asantidepressants.

Twenty years later, however, this idea wasconveniently forgotten as the selective sero-tonin reuptake inhibitors, of which fluoxe-tine (Prozac) is the best known, came to thefore. This apparent paradox perhaps revealsthe naivety of the simplistic monoaminetheories of the 1960s and 1970s, whichreached their peak with the notion of onemonoamine for each major illness: nor-adrenaline for depression, serotonin foranxiety, dopamine for schizophrenia andacetylcholine for dementia!

The antidepressant era represents one ofthe seminal events in the social and culturalhistory of the latter half of the twentieth cen-tury. This book is written in an individualand engaging style and the author reveals adeep knowledge of his subject; he has hisown firm views but does not force themupon the reader. I found it a compelling readand hope that it will reach a wideaudience.Leslie Iversen is in the Department ofPharmacology, University of Oxford, Oxford OX13QT, UK.

spring books

454 NATURE | VOL 392 | 2 APRIL 1998

Superpill: Prozac-takers felt “better than well”.

JOH

N G

RE

IM/S

CIE

NC

E P

HO

TO

LIB

RA

RY