Omega-3 fatty acids, in particular, eicosapentaenoic acid (EPA) have been suggested as augmentation strategies in the treatment of schizophrenia and related psychosis. Published results are conflicting, and the antipsychotic efficacy of such augmentation strategies is not well established.

Double-blind, randomized, placebo-controlled studies using purified or EPA-enriched oils in established schizophrenia were included in a meta-analysis. The effect size of EPA on psychotic symptoms was measured using Hedges' g. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was assessed with Q statistic and I index. Influence of moderators was assessed with meta-regression analyses in Comprehensive Meta-analysis Software version 2.

The database included 167 schizophrenic subjects under the placebo arm (mean age, 37 [SD, 9.7] years; 37% females) matched with 168 schizophrenic subjects under the EPA arm (mean age, 37 [SD, 7.9] years; 36% females) (t tests P > 0.05). Meta-analysis showed no consistent significant effect for the EPA augmentation on psychotic symptoms (Hedges' g = 0.242; 95% confidence interval, 0.028-0.512, Z = 1.7531, P > 0.05). There were no significant effects for moderator variables such as age, sex, and EPA dose used in the trials. Heterogeneity across studies was small and statistically non significant (Q = 9.06; P = 0.170; I = 33.81).

Meta-analysis of randomized controlled trials on symptomatic outcome revealed no beneficial effect of EPA augmentation in established schizophrenia. However, no conclusion can be made for medium- to long-term effects of EPA in schizophrenia, in particular on relapse prevention in the early course of psychotic disorders.