Selective serotonin reuptake inhibitors: Placebo washouts inflate antidepressant effects in general practice

doi:10.1136/bmj.330.7488.420-a

BMJ 2005;330:420 (19 February), doi:10.1136/bmj.330.7488.420-a

Letter

Selective serotonin reuptake inhibitors

Placebo washouts inflate antidepressant effects in general practice

The first 150 words of the full text of this article appear below.

EDITOR—Geddes and Cipriani fear that regulatory bodiesoverrate the importance of placebo controlled trials.¹ We disagree.The placebo controlled randomised trial is still the best testof efficacy available, although several improvements in conventionalmethodology are necessary to prevent selection biases.² However,selection bias owing to a placebo washout period has not yetbeen tackled.

Although no doctor uses a placebo washout in real life practice,most antidepressant trials use such a period before randomisation.To demonstrate their effect: say, 200 patients are available,and 20 placebo responders are excluded before randomisation.The remaining 180 patients are then randomised to treatmentwith antidepressant or placebo. However, as it is not knownwhether all placebo responders in the antidepressant arm wouldhave recovered if they had been given antidepressants, the directionof this differential selection may favour antidepressants.

Other necessary methodological improvements are: more use of"active" placebos to . . . [Full text of this article]

Harm W J van Marwijk, senior researcher, department of general practice

hwj.vanmarwijk@vumc.nl, Institute for Extramural Medicine, VU University Medical Centre, Van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands

Herman J Adèr, methodologist, department of clinical epidemiology and biostatistics

Institute for Extramural Medicine, VU University Medical Centre, Van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands