Meta-analysis of the placebo response in antidepressant trials

Abstract

Improvements in placebo groups of antidepressant trials account for a major part of the expected drug effects. We aimed to determine overall effect sizes of placebo and drug effects in antidepressant trials, and to analyze whether the placebo effect in antidepressant trials also occurs for patient self-perception, general psychopathology, and quality of life.

Methods: Search terms covered different variants of pharmacotherapy for patients with depressive disorders from January 1980 to December 2005 in the databases Medline/Pubmed, PsychInfo and CENTRAL, a.o. We included RCTs with a placebo group and an antidepressant group in people with depression.

Results: We computed within group effect sizes for several outcome variables and integrated them using random-effect models. A total of 96 studies were included. Mean effect size in the placebo group for primary outcome variables was d=1.69 (95% CI=1.54-1.84) compared to 2.50 in the drug group (95% CI=2.30-2.69). There was a major difference between placebo effect sizes assessed with observer ratings (d=1.85, 95% CI=1.69-2.01) versus patient self-perception (d=0.67; 95% CI=0.49-0.85). The effect sizes in placebo groups in 2005 were more than twice as great as those in 1980, but only for observer ratings, not for patient self-ratings. The result was partly due to increased homogeneity of samples of recently published trials.

Conclusions: The placebo effect accounted for 68% of the effect in the drug groups. Whereas clinical trials need to control the placebo effect, clinical practice should attempt to use its full power.