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Review Article

Review of Maintenance Trials for Major Depressive Disorder: A 25-Year Perspective From the US Food and Drug Administration

Silvana Borges, MD; Yeh-Fong Chen, PhD; Thomas P. Laughren, MD; Robert Temple, MD; Hiren D. Patel, PharmD; Paul A. David, RPh; Mitchell Mathis, MD; Ellis Unger, MD; Peiling Yang, PhD; and Ni A. Khin, MD

Published: March 15, 2014

Article 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.

J Clin Psychiatry 2014;75(3):205-214

Submitted: August 7, 2013; accepted November 27, 2013 (doi:10.4088/JCP.13r08722).

Corresponding author: Silvana Borges, MD, Division of Psychiatry Products, HFD-130, Food and Drug Administration, 10903 New Hampshire Ave, Bldg 22, Rm 4159, Silver Spring, MD 20993-0002 (

Volume: 75

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