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-including tricyclics and the newer Prozac-type drugs-involving 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 percent more effective than placebos. But Kirsch and Sapirstein found that the drugs were only 25 percent more effective. In addition, they suggest that even that 25 percent 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.
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's College London, agrees. "There's tremendous uncertainty about how they work," he says. "The public thinks the doctors know, but they don't. Any decent psychopharmacologist will tell you this."
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. "If patients know they're getting treatment, their expectation will be raised and with it their optimism that they will get better. It's a self-fulfilling prophecy." 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 "minuscule and unrepresentative" and amounted to "a failure of peer review".
Kirsch's and Sapirstein's work does not show that antidepressants have no pharmacological effect. However, Kirsch says the findings indicate "a pressing need for new methodologies in clinical trials" to discover the true extent of the placebo effect. One option might be to give some patients "active placebos" that cause side effects but have no medical effect.
The researchers' results also appear in the current issue of Prevention & Treatment, the American Psychological Association's electronic journal http://journals.apa.org/prevention/.