The Efficacy of Omega-3 Fatty Acids as the Monotherapy for Depression: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Objective: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have demonstrated protective effects in major depressive disorder (MDD) patients receiving antidepressant treatment. However, there have been a few double-blind randomized controlled trials focused on n-3 PUFAs as monotherapy in MDD, and the outcomes have been mixed. This study aimed to assess the clinical effects of n-3 PUFAs monotherapy in patients with MDD. Methods: A total of 60 patients with MDD participated in this 12-week double-blind randomized controlled trial. They were randomized to either the n-3 PUFAs group (n = 30; 3.2 g of eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA per day) or the placebo group (n = 30; 3.2 g of soybean oil per day). The severity of depression was evaluated using the Hamilton Rating Scale for Depression (HRSD). Results: The n-3 PUFAs group had a significantly lower HRSD score compared with the placebo group at week 4 (p = 0.004), week 6 (p = 0.006), week 8 (p = 0.004), and week 12 (p = 0.01). The n-3 PUFAs group showed slightly higher rates for both remission (26.7% vs. 10%, p = 0.095) and response (23.3% vs. 6.7%, p = 0.145) compared with the placebo group at week 12, but these differences did not reach statistical significance. Conclusions: These findings suggested that monotherapy of n-3 PUFAs could improve depression and potentially serve as an alternative option for MDD patients.