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Active placebos versus antidepressants for depression.

J Moncrieff¹, S Wessely, R Hardy

¹Psychiatry, University College London, Warley hospital, Mascalls Lane, Brentwood, Essex, UK, CM14 4TU.

The Cochrane Database of Systematic Reviews

|February 20, 2004

Summary

Antidepressant efficacy may be overestimated due to placebo effects in trials. Active placebos, mimicking side effects, showed smaller differences, suggesting unblinding biases conventional trials for depression treatment.

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Area of Science:

Psychiatry
Clinical Psychology
Pharmacology

Background:

Antidepressants are effective for depression, but placebo effects are substantial.
Side effects can unblind participants and researchers in trials using inert placebos.
Active placebos may mitigate bias by mimicking antidepressant side effects.

Purpose of the Study:

To investigate the efficacy of antidepressants compared to active placebos in depression treatment.

Main Methods:

Searched MEDLINE, PsychLIT, and EMBASE databases up to July 2000.
Included randomized and quasi-randomized controlled trials comparing antidepressants with active placebos.
Calculated standard effect sizes and conducted subgroup analyses for inpatient and outpatient trials.

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Main Results:

Nine studies with 751 participants were analyzed.
Two studies showed statistically significant differences favoring antidepressants.
Pooled effect size was 0.39 SD, but sensitivity analysis reducing heterogeneity yielded 0.17 SD.

Conclusions:

Differences between antidepressants and active placebos were small, suggesting potential overestimation of efficacy in inert placebo trials.
Unblinding effects may inflate perceived antidepressant efficacy.
Further research on unblinding in clinical trials is recommended.