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

Abstract

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.

Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress

“…Protein levels of sEH in the parietal cortex from depression, bipolar disorder, and schizophrenia were significantly higher than those on controls. One-way ANOVA showed the results [F (3,56) = 4.364, P = 0.008]. Data are shown as mean ± SEM (n = 15).…”

“…(D) Western blot analysis of sEH in the cerebellum from control (n = 15), depression (n = 15), bipolar disorder (n = 15), and schizophrenia (n = 15). Protein levels of sEH in the cerebellum from depression, bipolar disorder, and schizophrenia were not different among the four groups [F (3,56) =1.389, P = 0.256]. Data are shown as mean ± SEM (n = 15).…”

“…Many depressed patients become chronically ill, with several relapses (early return of symptoms within the expected duration of a current episode, of perhaps 3-12 mo) or later recurrences (new episodes) following initial short-term improvement or remission (55,56). Recurrence rates are over 85% within a decade of an index depressive episode, and average ∼50% or more within 6 mo of apparent clinical emission (56). Therefore, the prevention of relapse and recurrence is very important in the management of depression.…”

Soluble epoxide hydrolase: a new therapeutic target for depression

“…Many depressed patients become chronically ill, with several relapses (defined as an early return of symptoms within the expected duration of a current episode, of perhaps 3-12 months) or later recurrences (new episodes), following initial short-term improvement or remission [15]. Relapses occur at a rate of over 85% within a decade of an index depressive episode, and on average, approximately 50% or more within 6 months of an apparent clinical remission [15].…”

“…Relapses occur at a rate of over 85% within a decade of an index depressive episode, and on average, approximately 50% or more within 6 months of an apparent clinical remission [15]. Therefore, the prevention of relapse and recurrence is paramount in the management of depression.…”