Food and Behaviour Research

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Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder

Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini H, Jalali M, Peet M (2008) Australian and New Zealand Journal of Psychiatry 42(3) 192-198 

Web URL: View this and related abstracts via PubMed here


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

Sixty outpatients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score of at least 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.

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 (50% decrease in baseline HDRS) were 50%, 56% and 81% in the fluoxetine, EPA and combination groups, respectively.

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.


This randomised clinical trial found that treatment with the long-chain omega-3 fatty acid EPA alone was at least as effective as fluoxetine (Prozac) in the treatment of major depression, and also had fewer side-effects.  

However, the combination of the two led to significantly greater symptom reduction than either treatment alone (and yielded fewer side-effects than fluoxetine alone). 

See also the subsequent study investigating cortisol and other markers of stress and/or inflammation in the patients who took part in this treatment study: