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A growing number of observational and epidemiological studies have suggested that mental illness, in particular mood disorders, is associated with decreased dietary intake and/or cellular abundance of omega-3 polyunsaturated fatty acids (PUFA). This has prompted researchers to test the efficacy of omega-3 PUFA in a range of different psychiatric disorders. We have critically reviewed the double-blinded placebo controlled clinical trials published prior to April 2009 to determine whether omega-3 PUFA are likely to be efficacious in these disorders. Most trials involved a small number of participants but were largely well designed. Omega-3 PUFAs were well tolerated by both children and adults with mild gastrointestinal effects being the only consistently reported adverse event. There was little evidence of a robust clinically relevant effect for schizophrenia. In the case of attention deficit hyperactivity disorder (ADHD) and related disorders, most trials showed at most small benefits over placebo. A limited meta-analysis of these trials suggested that benefits of omega-3 PUFA supplementation may be greater in a classroom setting than at home. A meta-analysis of trials involving patients with major depressive disorder and bipolar disorder provided evidence that omega-3 PUFA supplementation reduces symptoms of depression. Furthermore, meta-regression analysis suggested that supplementation with eicosapentaenoic acid may be more beneficial in mood disorders than with docosahexaenoic acid (DHA); although several confounding factors prevented a definitive conclusion being made regarding which species of omega-3 PUFA is most beneficial. The mechanisms underlying the apparent efficacy of omega-3 PUFA in mood disorders compared to schizophrenia were discussed as is a rational for the possibly greater efficacy of eicosapentaenoic acid compared to docosahexaenoic acid. While it is not currently possible to recommend omega-3 PUFA as either a mono or adjunctive-therapy in any mental illnesses, the available evidence is strong enough to justify continued study, especially with regard to attention, anxiety and mood disorders.

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