Jazayeri · The Australian and New Zealand journal of psychiatry 2008 · double-blind randomized controlled trial · n=60

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

Cited 219 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 18247193 · doi:10.1080/00048670701827275 · record verified 2026-08-29

What was done

An 8-week, double-blind, double-dummy randomized controlled trial evaluated 60 outpatients with major depressive disorder (DSM-IV criteria, 17-item Hamilton Depression Rating Scale [HDRS] score ≥15). Participants were randomly assigned to receive daily 1000 mg eicosapentaenoic acid (EPA), 20 mg fluoxetine, or their combination. Assessments occurred every 2 weeks, with change in HDRS as the primary outcome. Analysis of covariance at week 8 with last observation carried forward was conducted on 48 patients who completed at least 4 weeks.

What was found

Treatment, age of onset, and baseline HDRS score significantly influenced HDRS at week 8. The EPA plus fluoxetine combination was significantly better than either monotherapy starting at week 4. Fluoxetine and EPA showed similar efficacy. Response rates (≥50% reduction in baseline HDRS) were 50% for fluoxetine alone, 56% for EPA alone, and 81% for the combination group.

Why it matters

The findings suggest EPA may be as effective as standard fluoxetine monotherapy and offer additive benefits when co-administered for major depressive disorder.

Limits

The study had a small sample size (60 randomized, 48 analyzed), a short duration of 8 weeks, significant attrition (12 dropouts before week 4), and lacked a pure placebo arm.

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