Meta-analysis : Effects of Eicosapentaenoic Acid in Clinical Trials in Depression

Objective—Randomized trials of omega-3 polyunsaturated fatty acid (PUFA) treatment for depression have differed in outcome. Recent meta-analyses ascribe discrepancies to differential effects of eicosapentaenoic acid (EPA) vs. docosahexaenoic acid (DHA) and to diagnostic heterogeneity. This meta-analysis tests the hypothesis that EPA is the effective component in PUFA treatment of major depressive episodes. Data Sources—PubMed was searched (1960 through June 2010) using terms “Fish Oils”[Mesh] AND (“Depressive Disorder”[Mesh] OR “Bipolar Depression”) AND “Randomized Controlled Trial”[Publication Type], for placebo-controlled trials of PUFA supplementation, a depressive episode as primary disorder, published in English, supplemented by manual bibliography review. Study Selection—The search yielded 15 trials involving 916 participants. Data Extraction—Sample sizes; PUFA doses; mean ages, baseline and endpoint depression ratings and standard deviations; and p values were extracted. Data Synthesis—In a mixed-effect model, percentage of EPA in the supplements was the fixedeffect predictor, dichotomized into two groups: EPA < 60% or EPA ≥ 60% of EPA + DHA. Secondary analyses explored relevance of treatment duration, age, and EPA dose. Results—Supplements with EPA ≥ 60% showed benefit on standardized mean depression scores (SMD, for EPA ≥ 60% = 0.558, 95% CI = (0.277, 0.838), z = 4.195, p = 0.001; for EPA < 60% = −0.026, 95% CI = (0.200, 0.148), z = −0.316, p =0.756), with negligible contribution of random effects or heteroscedasticity, and no effects of treatment duration or age. Supplements with EPA < 60% were ineffective. Exploratory analyses supported a non-linear model, with improvement determined by the dose of EPA in excess of DHA, within the range 200 to 2200 mg EPA. Conclusions—Supplements containing EPA ≥ 60%, in dose range 200 to 2200 mg EPA in excess of DHA, were effective against primary depression. Translational studies are needed to determine mechanisms of EPA’s therapeutic benefit.