Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: A randomized controlled trial

Context: Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids. Objective: To determine whether omega-3 improves the response to sertraline in patients with major depression and coronary heart disease (CHD). Design, Setting, and Participants: Randomized controlled trial. Between May 2005 and December 2008, 122 patients in St Louis, Missouri, with major depression and CHD were randomized. Interventions: After a 2-week run-in period, all patients were given 50 mg/d of sertraline and randomized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters (930 mg of eicosapentaenoic acid [EPA] and 750 mg of docosahexaenoic acid [DHA]) (n=62) or to corn oil placebo capsules (n=60) for 10 weeks. Main Outcome Measures: Scores on the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HAM-D). Results: Adherence to the medication regimen was 97% or more in both groups for both medications. There were no differences in weekly BDI-II scores (treatment x time interaction=0.02; 95% confidence interval [CI], -0.33 to 0.36; t₁₁₂=0.11; P=.91), prepost BDI-II scores (placebo, 14.8 vs omega-3, 16.1; 95% difference-in-means CI, -4.5 to 2.0; t₁₁₆=-0.77; P=.44), or HAM-D scores (placebo, 9.4 vs omega-3, 9.3; 95% difference-in-means CI, -2.2 to 2.4; t₁₁₅=0.12; P=.90). The groups did not differ on predefined indicators of depression remission (BDI-II ≤8: placebo, 27.4% vs omega-3, 28.3%; odds ratio [OR], 0.96; 95% CI, 0.43-2.15; t₁₁₃=-0.11; P=.91) or response (>50% reduction in BDI-II from baseline: placebo, 49.0% vs omega-3, 47.7%; OR, 1.06; 95% CI, 0.51-2.19; t₁₁₂=0.15; P=.88). Conclusions: Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks, compared with sertraline and placebo. Whether higher doses of omega-3 or sertraline, a different ratio of EPA to DHA, longer treatment, or omega-3 monotherapy can improve depression in patients with CHD remains to be determined. Trial Registration: clinicaltrials.gov Identifier: NCT00116857.