A Double-Blind, Randomized Controlled Clinical Trial Comparing Eicosapentaenoic Acid Versus Docosahexaenoic Acid for Depression

David Mischoulon, MD, PhD; Andrew A. Nierenberg, MD; Pamela J. Schettler, PhD; Becky L. Kinkead, PhD; Kiki Fehling, BA; Max A. Martinson, BA; and Mark Hyman Rapaport, MD

Published: September 16, 2014

Article Abstract

Objective: To compare 2 omega-3 (n-3) preparations enriched with eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) as monotherapy for major depressive disorder (MDD) in a 2-site, placebo-controlled, randomized, double-blind clinical trial.

Method: 196 adults (53% female; mean [SD] age = 44.7 [13.4] years) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 15 were randomized equally from May 18, 2006, to June 30, 2011, to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d, DHA-enriched n-3 1,000 mg/d, or placebo.

Results: 154 subjects completed the study. Modified intent-to-treat (mITT) analysis (n = 177 subjects with ≥ 1 postbaseline visit; 59.3% female, mean [SD] age 45.8 [12.5] years) employed mixed-model repeated measures (MMRM). All 3 groups demonstrated statistically significant improvement in the HDRS-17 (primary outcome measure), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16), and Clinical Global Improvement-Severity Scale (CGI-S) (P < .05), but neither n-3 preparation separated from placebo (P > .05). Response and remission rates were in the range of 40%-50% and 30%, respectively, for all treatments, with no significant differences between groups. One subject receiving EPA-enriched n-3 discontinued due to worsening depression, and 1 subject receiving placebo discontinued due to an unspecified “negative reaction” to pills.

Conclusions: Neither EPA-enriched nor DHA-enriched n-3 was superior to placebo for the treatment of MDD.

Trial Registration: ClinicalTrials.gov identifier: NCT00517036

Volume: 76

Quick Links: Depression (MDD)

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