THE benefits of antidepressant drugs could be almost entirely due to the
psychological boost derived from taking a pill rather than their effects on
brain chemistry, say two researchers in the US.
Irving Kirsch of the University of Connecticut and Guy Sapirstein of Westwood
Lodge Hospital, Needham, analysed 19 studies on selected antidepressants and
sedatives鈥攊ncluding tricyclics and the newer Prozac-type
drugs鈥攊nvolving 2318 patients. In each study, the patients had been given
either an active drug or a chemically inactive placebo, and their psychological
conditions had been evaluated at the beginning and end.
Pharmaceuticals companies claim that antidepressants are 40 per cent more
effective than placebos. But Kirsch and Sapirstein found that the drugs were
only 25 per cent more effective. In addition, they suggest that even that 25 per
cent could be due to an additional placebo effect derived from the side effects
caused by the antidepressants, which alerted patients to the fact that they were
receiving an active drug rather than a placebo. They say that the studies could
have wrongly ascribed this additional effect to a chemical change induced by the
drugs.
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Their analysis also suggests that antidepressants offer no advantage over
drugs such as anxiolytics and tranquillisers, which adds fuel to the suspicion
that the newer antidepressants are not as specific in their actions as their
manufacturers claim.
Simon Wessely, professor of psychiatry at King鈥檚 College London, agrees.
鈥淭here鈥檚 tremendous uncertainty about how they work,鈥� he says. 鈥淭he public
thinks the doctors know, but they don鈥檛. Any decent psychopharmacologist will
tell you this.鈥�
Wessely says Kirsch and Sapirstein are right to point out that side effects
can alert a patient in a trial to the fact they are getting an active drug
rather than a placebo. 鈥淚f patients know they鈥檙e getting treatment, their
expectation will be raised and with it their optimism that they will get better.
It鈥檚 a self-fulfilling prophecy.鈥� On the basis of this study and one that
Wessely participated in (British Journal of Psychiatry, vol 172, p
227), he believes that the advantage antidepressants offer over placebos is just
15 to 20 per cent.
But a psychiatrist commentating on the new analysis in the latest issue of
Prevention & Treatment is fiercely critical of the paper.
Donald Klein of Columbia University, New York, who played a major role in
developing antidepressant treatments, says the work is flawed because the group
of trials chosen was 鈥渕inuscule and unrepresentative鈥� and amounted to 鈥渁 failure
of peer review鈥�.
Kirsch鈥檚 and Sapirstein鈥檚 work does not show that antidepressants have no
pharmacological effect. However, Kirsch says the findings indicate 鈥渁 pressing
need for new methodologies in clinical trials鈥� to discover the true extent of
the placebo effect. One option might be to give some patients 鈥渁ctive placebos鈥�
that cause side effects but have no medical effect.
The researchers鈥� results also appear in the current issue of Prevention
& Treatment, the American Psychological Association鈥檚 electronic
journal (http://journals.apa.org/prevention/).