Food and Behaviour Research

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

Sublette ME, Ellis SP, Geant AL, Mann JJ (2011) J Clin Psychiatry. 2011 Dec;72(12):1577-84.   

Web URL: View this and related abstracts on PubMed here.

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.

FAB RESEARCH COMMENT:

Results from clinical trials of 'omega-3 fatty acids' for depression have been variable, with many trials reporting benefits, but others not.

The aim of this study was to find out if benefits varied according to the proportion of EPA rather than DHA provided by the supplements, as others have already suggested (see Martins et al 2009)

As predicted, high-EPA formulations (where EPA made up at least 60% of the omega-3 HUFA) were found to be effective in reducing depressive symptoms, By contrast, formulations richer in DHA (EPA < 60% of total EPA+DHA) were not effective.