Meta-Analysis of the Effects of Eicosapentaenoic Acid (EPA) in Clinical Trials in Depression

New York State Psychiatric Institute, New York, NY 10032, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 09/2011; 72(12):1577-84. DOI: 10.4088/JCP.10m06634
Source: PubMed


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.
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.
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.
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.
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.
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.
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.

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Available from: J. John Mann, Aug 11, 2014
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    • "Downloaded by [UNICAMP] at 08:25 24 November 2015 In conclusion, Omega-3 and -6 PUFAs are molecular modulators of neurotransmission and inflammation. Some evidence indicates that eicosapentaenoic acid (EPA) is the active n- 3 PUFA responsible for mood-altering effects in n-3 PUFA supplementation studies of depression (Sublette et al. 2011; Sarris et al. 2012). Lower n-3 PUFAs have been seen in a number of clinical studies of BD, particularly in erythrocyte studies (McNamara et al. 2010). "
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    • "However, the effect of these PUFA treatments later in childhood is not clear [33] [34]. Lower post-mortem brain DHA is present in major depressive disorder relative to controls [35] [36] [37], however, supplemental EPA, but not DHA, appears to be effective in the management of depressive symptoms [38] [39]. Table 1 Summary of published studies that have used stable-isotope labeled ALA to measure DHA synthesis. "

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    • "Consistent with case-control studies of PUFA levels in human tissues, omega-3 PUFAs have been reported to be effective in treatment of MDD. Six meta-analytic reviews from four independent groups have reported on the antidepressant effect of PUFAs [17] [18] [19] [20] [21] [22], yet three previous meta-analyses from the two of the four groups did not support these effects in heterogeneous populations (such as subclinical subjects in community samples) [23] [24] [25] [26]. Negative findings must be interpreted with caution due to limitations: e.g., differing mood assessments, pooling heterogeneous populations, and implementing different intervention methods. "
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