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Omega-3 ratio for positive depression effect is 60% or more EPA

  [ 15 votes ]   [ Discuss This Article ] • November 25, 2011

Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression – Source: Journal of Clinical Psychiatry, Sep 6, 2011

By M Elizabeth Sublette, MD, PhD, et al.

[Note: The full text pdf of this article can be found at It includes a discussion of various hypotheses regarding why these EPA-DHA ratios and relative daily amounts provide therapeutic benefit for primary depression. DHA & EPA are found mainly in fish oil. ]

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 less than 60% or EPA 60% or more of the total EPA + DHA. Secondary analyses explored the relevance of treatment duration, age, and EPA dose.


• Supplements with 60% or more EPA [of total EPA + DHA] 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 less than 60% EPA (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 less than 60% EPA 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.


• Supplements containing 60% or more EPA 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.

Source: Journal of Clinical Psychiatry, Sep 6, 2011. PMID:21939614, by Sublette ME, Ellis SP, Geant AL, Mann JJ. New York State Psychiatric Institute, New York, NY, USA. [Email:]

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