Scientific Publications by FDA Staff

J Clin Psychiatry 2014 Mar;75(3):205-14

Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration.

Borges S, Chen YF, Laughren TP, Temple R, Patel HD, David PA, Mathis M, Unger E, Yang P, Khin NA

OBJECTIVE: The maintenance efficacy of antidepressants is usually assessed in postmarketing studies with a randomized withdrawal design. This report explores differences in relapse rates, trial characteristics, and success rates in maintenance efficacy studies submitted to the US Food and Drug Administration (FDA) over a 25-year period. DATA SOURCES: Clinical data from all maintenance trials with antidepressants submitted to FDA between 1987 and 2012. STUDY SELECTION: Efficacy data were compiled from 15 maintenance clinical trials in adults diagnosed with major depressive disorder according to DSM-III or DSM-IV criteria. DATA EXTRACTION: Trial characteristics, relapse rates, and time to relapse in each study were examined. RESULTS: Relapse rates were significantly lower (P < .05) in the drug arm than in the placebo arm in every study, with a mean relapse rate difference of 18% and an average percent reduction in relapse rate of 52% compared to placebo. Only 6% of the relapse events occurred in the first 2 weeks of the double-blind phase. The separation between treatment arms continued to increase throughout the double-blind phase only in the trial with longest response stabilization period. CONCLUSIONS: Antidepressant maintenance trials have a high rate of success, indicating a benefit of continuing drug treatment after initial response to an antidepressant. This benefit appears to result mainly from a decreased rate of recurrent depression rather than from an effect of drug withdrawal in the placebo groups.