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.