Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression

Background Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings. Aims To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials. Method A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo. Results Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge's G = 0.61, P<0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression. Conclusions Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.