Twenty-eight patients (aged 18-60 years) with major depression were randomly assigned to receive, in double-blind fashion, menhaden oil (providing 4.4 g/day of eicosapentaenoic acid and 2.2 g/day of docosahexaenoic acid) or placebo for eight weeks. All patients except one in each group had been receiving antidepressant medication for at least four weeks and continued on those medications during the trial. The improvement in symptoms, as determined by a lower score on the 21-item Hamilton Rating Scale for Depression (HAM-D), was significantly greater in the active-treatment group than in the placebo group after four (p < 0.005), six (p = 0.001) and eight (p = 0.001) weeks. After 8 weeks, the mean reduction in the HAM-D score was approximately 14 points in the active-treatment group, compared with approximately 6 points in the placebo group (p = 0.001).

Comment: In this study, supplementation with omega-3 fatty acids from fish (menhaden) oil, as an adjuvant to antidepressant medication, was beneficial in the treatment of major depression. Previous studies using either fish oil or purified EPA (administered as the ethyl-ester of EPA) have found similar results, although purified docosahexaenoic acid given by itself was ineffective. Thus, the beneficial effects seen with fish oil appear to be due to the EPA component. Depression is associated with low concentrations of omega-3 fatty acids in plasma and red blood cells. EPA is believed to modulate mood through an effect on cell membranes and on signal transduction systems.

Su KP, et al. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 2003;13:267-271.