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

J Clin Psychiatry. 2014 Mar;75(3):205-14. doi: 10.4088/JCP.13r08722.

Abstract

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.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adult
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / prevention & control
  • Female
  • Humans
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Secondary Prevention
  • Time Factors
  • Treatment Outcome*
  • United States
  • United States Food and Drug Administration / statistics & numerical data*
  • Withholding Treatment / statistics & numerical data*