Omega3 fish oil EPA as effective as Prozac in the treatment of medium to major depression

EPA Plus Prozac Better Than Either Treatment Alone for Major Depression

Long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs) have been used as an adjunct therapy in treating patients with major depressive disorder with mixed, but often encouraging, results. A meta-analysis of placebo-controlled trials concluded that n-3 PUFAs have significant antidepressant effects, but there are insufficient data to distinguish whether combined treatment with the two major n-3 LC-PUFAs in fish oils, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or each fatty acid given individually provides greater benefit. Studies have tended to find positive results with EPA rather than DHA and a rationale for this observation has been suggested. In most, if not all, trials to date, n-3 LC-PUFAs have been provided in conjunction with current antidepressant medications. Difficulties with patient compliance, unwanted or adverse side effects of medications and resistance to treatment make treating depression especially challenging.

In this study, Shima Jazayeri and colleagues at the Tehran University of Medical Sciences in Iran sought to evaluate the effectiveness of fluoxetine (Prozac), EPA or a combination of them in patients with major depressive disorder as indicated by Hamilton Depression Rating Scale scores of 15 or greater. Patients did not have other psychiatric disorders or any other significant medical problems or substance abuse. They were not taking n-3 PUFA supplements nor eating more than one serving of fish/week. All participants were free of medication for at least 6 weeks prior to enrolment.

Sixty patients were recruited from referrals to the Roozbeh Psychiatric Hospital in Tehran and randomized to consume 20 mg of fluoxetine or 1 g EPA or a combination daily for 8 weeks. Each participant consumed either a fluoxetine placebo or a rapeseed oil placebo to mimic the type of capsules taken in each group. No placebo-only group was included for ethical reasons. Patients were assessed by the Hamilton Scales at baseline and every 2 weeks thereafter. Of the 60 patients enrolled, 48 completed at least 4 weeks of the study.

Over the course of the 8-week study, all patient groups exhibited significant reductions in their Hamilton depression scores as early as 2 weeks from baseline. Scores for patients treated with fluoxetine or EPA did not differ throughout the study. At 4 and 6 weeks, those consuming both EPA and fluoxetine showed a significantly greater improvement in their Hamilton ratings (as determined by analysis of covariance) compared with either treatment alone. Depression scores continued to improve from the 4th to the 8th week. Response rates for achieving at least a 50% reduction in depression score were 50% for fluoxetine, 56% for EPA and 81% for those taking both fluoxetine and EPA. More adverse events occurred in the fluoxetine and combination groups than in the EPA group and ranged from gastro-intestinal effects, anxiety and decreased appetite to single reports of tremor, nightmare and constipation.

These results suggest a greater improvement in depression with the combination of EPA and fluoxetine, but the effects of either one alone may have been no different from a placebo, had there been one. Other studies have reported a placebo effect of trial participation. This study supports those that have reported significant improvement in depression using a modest dose (1 g/day) of EPA as an adjunct treatment to current medication.

Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini H, Jalali M, Peet M. Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry 2008;42:192-198. [PubMed]

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