Eicosapentaenoic acid versus docosahexaenoic acid in mild-to-moderate depression: A randomized, double-blind, placebo-controlled trial

Abstract Controversy exists as to whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or both are responsible for the efficacy of n-3 polyunsaturated fatty acids in depression. We conducted a single-center, randomized, double-blind, placebo-controlled, multi-arm, parallel-group trial, comparing the efficacy of EPA versus DHA as adjuvants to maintenance medication treatments for mild-to-moderate depression. Eighty-one mild-to-moderately depressed outpatients were randomly assigned to receive either 1 g/d of EPA or DHA or placebo (coconut oil) for 12 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS) final score in the modified intention-to-treat population, which comprised of all randomized patients with at least 1 post-randomization observation ( n =62; 61.3% female; mean age 35.1±1.2 years). Allocated treatments were well tolerated. Although there was no significant difference between groups at baseline, patients in the EPA group showed a significantly lower mean HDRS score at study endpoint compared with those in the DHA ( p