Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial.

Double-blind, placebo-controlled randomized clinical trial conducted in Canada in women aged 40 to 55 years with moderate-to-severe psychological distress during the menopausal transition. The E-EPA arm had 59 participants randomized; women with severe major depressive episodes were excluded, and some participants had a history of major depressive episodes. Outcomes included psychological well-being and depressive symptom scales over 8 wk.

Participants received oral ethyl-eicosapentaenoic acid (E-EPA) capsules, 3 daily for 8 wk, for a total daily dose of 1.05 g EPA and 0.15 g DHA. Each 500-mg capsule contained 350 mg EPA and 50 mg DHA as ethyl esters; the comparator was placebo sunflower oil with 0.2% regular fish oil added to better match taste.

E-EPA did not show a significant overall benefit over placebo for psychological distress or depressive symptoms in the full sample. Adjusted 8-wk between-group differences were not significant for PGWB, 3.3 (95% CI: -2.9, 9.6; P = 0.2908), HSCL-D-20, -0.08 (95% CI: -0.27, 0.12; P = 0.4311), or HAM-D-21, -1.5 (95% CI: -3.7, 0.7; P = 0.1686). In women without major depressive episode at baseline (n = 91), E-EPA was associated with greater improvement on PGWB, 8.0 (95% CI: 0.6, 15.3; P = 0.034), HSCL-D-20, -0.2 (95% CI: -0.4, -0.01; P = 0.040), and HAM-D-21, -2.7 (95% CI: -5.1, -0.3; P = 0.030), but this subgroup finding was not seen in women with baseline MDE. Adverse events were more frequent with E-EPA than placebo, 40.0% vs 19.6% (P = 0.034).

The intervention was short term (8 wk) and the active arm was relatively small, limiting power for the primary analysis and especially for subgroup comparisons. Benefits were confined to a post hoc or stratified subgroup without baseline MDE, which reduces certainty and generalizability. The sample was restricted to middle-aged mostly white women with menopausal-transition distress, and adverse events were more common with E-EPA.