Prevention of Relapse and Recurrence in Adults with Major Depressive Disorder: Systematic Review and Meta-Analyses of Controlled Trials.

BACKGROUND: Findings of substantial remaining morbidity in treated major depressive disorder (MDD) led us to review controlled trials of treatments aimed at preventing early relapses or later recurrences in adults diagnosed with MDD to summarize available data and to guide further research. METHODS: Reports (n = 97) were identified through systematic, computerized literature searching up to February 2015. Treatment versus control outcomes were summarized by random-effects meta-analyses. RESULTS: In 45 reports of 72 trials (n = 14 450 subjects) lasting 33.4 weeks, antidepressants were more effective than placebos in preventing relapses (response rates [RR] = 1.90, confidence interval [CI]: 1.73-2.08; NNT = 4.4; p < 0.0001). In 35 reports of 37 trials (n = 7253) lasting 27.0 months, antidepressants were effective in preventing recurrences (RR = 2.03, CI 1.80-2.28; NNT = 3.8; p < 0.0001), with minor differences among drug types. In 17 reports of 22 trials (n = 1 969) lasting 23.7 months, psychosocial interventions yielded inconsistent or inconclusive results. CONCLUSIONS: Despite evidence of the efficacy of drug treatment compared to placebos or other controls, the findings further underscore the substantial, unresolved morbidity in treated MDD patients and strongly encourage further evaluations of specific, improved individual and combination therapies (pharmacological and psychological) conducted over longer times, as well as identifying clinical predictors of positive or unfavorable responses and of intolerability of long-term treatments in MDD.

Duration of initial antidepressant treatment and subsequent relapse of major depression.

BACKGROUND: The efficacy, limitations, and methods of studying antidepressant treatment continued beyond initial weeks of acute major depression remain incompletely resolved. AIMS: For subjects treated in controlled trials for acute depression, we analyzed the relationship of relapse risk within 12 months of rerandomizing to placebo versus duration of initial treatment and putative stabilization. METHODS: With data from placebo arms of 45 relevant controlled trials identified in recent, systematic reviews were pooled and analyzed by regression modeling. RESULTS: There was a strong inverse correlation of shorter initial treatment and greater relapse risk after rerandomizing to placebo treatment, best fit to a power function (P ≤ 0.003); relapse risk differed by 11.4-fold, declining sharply as initial treatment continued for 16 to 20 weeks or more. CONCLUSIONS: Discontinuation of antidepressant treatment for major depressive episodes at times less than 6 months was associated with rising risks after randomization to continuation with placebo. This relationship requires critical consideration in both clinical management of depressed patients and the design and interpretation of treatment discontinuation trials.