The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration.

This article reports an analysis of the efficacy data submitted to the U.S. Food and Drug Administration for approval of the 6 most widely prescribed antidepressants approved between 1987 and 1999. Approximately 80% of the response to medication was duplicated in placebo control groups, and the mean difference between drug and placebo was approximately 2 points on the 17-item (50-point) and 21-item (62-point) Hamilton Depression Scale. Improvement at the highest doses of medication was not different from improvement at the lowest doses. The proportion of the drug response duplicated by placebo was significantly greater with observed cases (OC) data than with last observation carried forward (LOCF) data. If drug and placebo effects are additive, the pharmacological effects of antidepressants are clinically negligible. If they are not additive, alternative experimental designs are needed for the evaluation of antidepressants.