The Efficacy of Omega-3 Supplementation for Major Depression: A Randomized Controlled Trial

Objective: To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode (MDE).

Method: Inclusive, double-blind, randomized, controlled, 8-week, parallel-group trial, conducted October 17, 2005 through January 30, 2009 in 8 Canadian academic and psychiatric clinics. Adult outpatients (N = 432) with MDE (Mini-International Neuropsychiatric Interview, version 5.0.0, criteria) lasting at least 4 weeks, including 40.3% taking antidepressants at baseline, were randomly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid (EPA) and 150 mg/d of docosahexaenoic acid (DHA) or matched sunflower oil placebo (2% fish oil). The primary outcome was the self-report Inventory of Depressive Symptomatology (IDS-SR30); the secondary outcome was the clinician-rated Montgomery-Šsberg Depression Rating Scale (MADRS).

Results: The adjusted mean difference between treatment and placebo was 1.32 points (95% CI, -0.20 to 2.84; P = .088) on the IDS-SR30 and 0.97 points (95% CI, -0.012 to 1.95; P = .053) on the MADRS. Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group (P = .035). For patients without comorbid anxiety disorders (n = 204), omega-3 supplementation was superior to placebo, with an adjusted mean difference of 3.17 points on the IDS-SR30 (95% CI, 0.89 to 5.45; P = .007) and 1.93 points (95% CI, 0.50 to 3.36; P = .008) on the MADRS.

Conclusions: In this heterogeneous sample of patients with MDE, there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms. However, there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders.

Trial Registration: controlled-trials.com Identifier: ISRCTN47431149

J Clin Psychiatry 2011;72(8):1054-1062

Submitted: January 7, 2010; accepted February 23, 2010.

Online ahead of print: June 15, 2010 (doi:10.4088/JCP.10m05966blu).

Corresponding author: François Lespérance, MD, Department of Psychiatry, Centre Hospitalier de l’ Université de Montréal, 1560 Sherbrooke E, Montreal, Quebec H2L 4M1, Canada (francois.lesperance@umontreal.ca).