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


METHODS
Clinical data from all maintenance trials with antidepressants submitted to FDA between 1987 and 2012.


METHODS
Efficacy data were compiled from 15 maintenance clinical trials in adults diagnosed with major depressive disorder according to DSM-III or DSM-IV criteria.


METHODS
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.
Division of Psychiatry Products, HFD-130, Food and Drug Administration, 10903 New Hampshire Ave, Bldg 22, Rm 4159, Silver Spring, MD 20993-0002 silvana.borges@fda.hhs.gov.
Silvana
S
Borges
Yeh-Fong
YF
Chen
Thomas P
TP
Laughren
Robert
R
Temple
Hiren D
HD
Patel
Paul A
PA
David
Mitchell
M
Mathis
Ellis
E
Unger
Peiling
P
Yang
Ni A
NA
Khin
D000328:Adult; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration / Q000706:statistics & numerical data*; D028761:Withholding Treatment / Q000706:statistics & numerical data*