OBJECTIVE: To compare therapeutic effects of eicosapentaenoic acid (EPA), fluoxetine and a combination of them in major depression.

METHOD: Sixty outpatients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score >or=15 in the 17-item Hamilton Depression Rating Scale (HDRS) were randomly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine, or their combination for 8 weeks. Double dummy technique was used to double blind the study. Patients were assessed at 2 week intervals. Change in HDRS was the primary outcome measure.

RESULTS: Analysis of covariance for HDRS at week 8 across treatment groups was performed in 48 patients who completed at least 4 weeks of the study, with the last observation carried forward. Treatment, age of onset and baseline HDRS had a significant effect on HDRS at week 8. EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment. Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms. Response rates (>or=50% decrease in baseline HDRS) were 50%, 56% and 81% in the fluoxetine, EPA and combination groups, respectively.

CONCLUSIONS: In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder. EPA + fluoxetine combination was superior to either of them alone.