A Randomized Placebo-Controlled Trial of Omega-3 and Sertraline in Depressed Patients With or at Risk for Coronary Heart Disease

OBJECTIVE: Studies of depressed psychiatric patients have suggested that antidepressant efficacy can be increased by adding eicosapentaenoic acid (EPA), one of the omega-3 fatty acids found in fish oils. The purpose of this study was to determine whether the addition of EPA improves the response to sertraline in depressed patients with or at high risk for coronary heart disease (CHD). METHODS: Between May 2014 and June 2018, 144 patients with DSM-5 major depressive disorder seen at the Washington University School of Medicine with or at high risk for CHD were randomized to receive either 50 mg/d of sertraline and 2 g/d of EPA or 50 mg/d of sertraline and corn oil placebo capsules for 10 weeks. The Beck Depression Inventory II (BDI-II) was the primary outcome measure. RESULTS: After 10 weeks of treatment, there were no differences between the arms on the mean baseline-adjusted BDI-II (placebo, 10.3; EPA, 12.1; P = .22), the 17-item Hamilton Depression Rating Scale (placebo, 7.2; EPA, 8.0; P = .40), or the 10-week remission rate (BDI-II score ≤ 8: placebo, 50.6%; EPA, 46.7%; odds ratio = 0.85; 95% CI, 0.43 to 1.68; P = .63). CONCLUSIONS: Augmentation of sertraline with 2 g/d of EPA for 10 weeks did not result in greater improvement in depressive symptoms compared to sertraline and corn oil placebo in patients with major depressive disorder and CHD or CHD risk factors. Identifying the characteristics of cardiac patients whose depression may benefit from omega-3 and clarifying the pathways linking omega-3 to improvement in depression symptoms are important directions for future research. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02021669; FDA IND registration number: 121107.