A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs.

In depressed patients, low blood levels of eicosapentaenoic acid are seen. We tested the antidepressive effect of ethyl-eicosapentaenoate in these patients. We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a standard antidepressant. Patients were randomized on a double-blind basis to placebo or ethyl-eicosapentaenoate at dosages of 1, 2, or 4 g/d for 12 weeks in addition to unchanged background medication. Patients underwent assessment using the 17-item Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, and the Beck Depression Inventory. Forty-six (88%) of 52 patients receiving ethyl-eicosapentaenoate and 14 (78%) of 18 patients receiving placebo completed the 12-week study with no serious adverse events. The 1-g/d group showed a significantly better outcome than the placebo group on all 3 rating scales. In the intention-to-treat group, 5 (29%) of 17 patients receiving placebo and 9 (53%) of 17 patients receiving 1 g/d of ethyl-eicosapentaenoate achieved a 50% reduction on the Hamilton Depression Rating Scale score. In the per-protocol group, the corresponding figures were 3 (25%) of 12 patients for placebo and 9 (69%) of 13 patients for the 1-g/d group. The 2-g/d group showed little evidence of efficacy, whereas the 4-g/d group showed nonsignificant trends toward improvement. All of the individual items on all 3 rating scales improved with the 1-g/d dosage of ethyl-eicosapentaenoate vs placebo, with strong beneficial effects on items rating depression, anxiety, sleep, lassitude, libido, and suicidality. Treatment with ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in treating depression in patients who remained depressed despite adequate standard therapy.