title: Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: New York State Psychiatric Institute, New York, NY 10032, USA. es2316@columbia.edu
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sublette
authors.forename: Steven P
authors.initials: SP
authors.lastname: Ellis
authors.forename: Amy L
authors.initials: AL
authors.lastname: Geant
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D003865:Major Depressive Disorder / Q000188:drug therapy*; D004281:Docosahexaenoic Acids / Q000627:therapeutic use; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D006801:Humans; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000639:trends; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid