Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression

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#major-depressive-disorder #docosahexaenoic-acids #eicosapentaenoic-acid #humans #placebos

Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression

Sublette et al., 2011 | J Clin Psychiatry | Meta Analysis

Citation

Sublette M Elizabeth, Ellis Steven P, ... Mann J John. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry. 2011-Dec;72(12):1577-84. doi:10.4088/JCP.10m06634

Abstract

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) versus 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/MeSH was searched for studies published in English from 1960 through June 2010 using the terms fish oils (MeSH) AND (depressive disorder [MeSH] OR bipolar depression) AND randomized controlled trial (publication type). The search was supplemented by manual bibliography review and examination of relevant review articles. STUDY SELECTION: The search yielded 15 trials involving 916 participants. Studies were included if they had a prospective, randomized, double-blinded, placebo-controlled study design; if depressive episode was the primary complaint (with or without comorbid medical conditions); if omega-3 PUFA supplements were administered; and if appropriate outcome measures were used to assess depressed mood. DATA EXTRACTION: Extracted data included study design, sample sizes, doses and percentages of EPA and DHA, mean ages, baseline and endpoint depression ratings and standard deviations for PUFA and placebo groups, and P values. The clinical outcome of interest was the standardized mean difference in the change from baseline to endpoint scores on a depression rating scale in subjects taking PUFA supplements versus subjects taking placebo. DATA SYNTHESIS: In a mixed-effect model, percentage of EPA in the supplements was the fixed-effect predictor, dichotomized into 2 groups: EPA < 60% or EPA ≥ 60% of the total EPA + DHA. Secondary analyses explored the relevance of treatment duration, age, and EPA dose. RESULTS: Supplements with EPA ≥ 60% showed benefit on standardized mean depression scores (effect size = 0.532; 95% CI, 0.277-0.733; t = 4.195; P < .001) versus supplements with EPA < 60% (effect size = -0.026; 95% CI, -0.200 to 0.148; t = -0.316; P = .756), with negligible contribution of random effects or heteroscedasticity and with no effects of treatment duration or age. Supplements with EPA < 60% were ineffective. Exploratory analyses supported a nonlinear model, with improvement determined by the dose of EPA in excess of DHA, within the range of 200 to 2,200 mg/d of EPA. CONCLUSIONS: Supplements containing EPA ≥ 60% of total EPA + DHA, in a dose range of 200 to 2,200 mg/d of EPA in excess of DHA, were effective against primary depression. Translational studies are needed to determine the mechanisms of EPA's therapeutic benefit.

Key Findings

Supplements with EPA ≥ 60% showed benefit on standardized mean depression scores (effect size = 0.532; 95% CI, 0.277-0.733; t = 4.195; P < .001) versus supplements with EPA < 60% (effect size = -0.026; 95% CI, -0.200 to 0.148; t = -0.316; P = .756), with negligible contribution of random effects or heteroscedasticity and with no effects of treatment duration or age. Supplements with EPA < 60% were ineffective. Exploratory analyses supported a nonlinear model, with improvement determined by the d

Outcomes Measured

  • depression

Population

Field Value
Population See abstract
Sample Size 916
Age Range See abstract
Condition depression

MeSH Terms

  • Major Depressive Disorder
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Humans
  • Placebos
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Comparative Study, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
  • Vertical: omega-3

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09