Food and Behaviour Research

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A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs

Peet M, Horrobin DF. (2002) Archives of General Psychiatry 59(10) 913-9 

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Abstract:

BACKGROUND: In depressed patients, low blood levels of eicosapentaenoic acid are seen. We tested the antidepressive effect of ethyl- eicosapentaenoate in these patients.

METHODS: We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a standard antidepressant. Patients were randomized on a double- blind basis to placebo or ethyl-eicosapentaenoate at dosages of 1, 2, or 4 g/d for 12 weeks in addition to unchanged background medication. Patients underwent assessment using the 17-item Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, and the Beck Depression Inventory.

RESULTS: Forty-six (88%) of 52 patients receiving ethyl-eicosapentaenoate and 14 (78%) of 18 patients receiving placebo completed the 12-week study with no serious adverse events. The 1-g/d group showed a significantly better outcome than the placebo group on all 3 rating scales. In the intention-to-treat group, 5 (29%) of 17 patients receiving placebo and 9 (53%) of 17 patients receiving 1 g/d of ethyl-eicosapentaenoate achieved a 50% reduction on the Hamilton Depression Rating Scale score. In the per-protocol group, the corresponding figures were 3 (25%) of 12 patients for placebo and 9 (69%) of 13 patients for the 1-g/d group. The 2-g/d group showed little evidence of efficacy, whereas the 4-g/d group showed nonsignificant trends toward improvement. All of the individual items on all 3 rating scales improved with the 1-g/d dosage of ethyl-eicosapentaenoate vs placebo, with strong beneficial effects on items rating depression, anxiety, sleep, lassitude, libido, and suicidality.

CONCLUSION: Treatment with ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in treating depression in patients who remained depressed despite adequate standard therapy.

FAB RESEARCH COMMENT:

UPDATE 2016:

This pioneering randomised controlled trial (RCT) was one of the very first to show that dietary supplementation with the long-chain omega-3 EPA could be an effective treatment for depression.

Many such clinical trials have been conducted since, with a consensus emerging that EPA (but not DHA) can indeed reduce depressive symptoms in patients with clinical depression.

Findings also suggest that these beneficial effects of EPA may be greater in patients taking standard antidepressant medications. See:

Sarris et al 2016 - Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses

Mocking et al 2016 - Meta-analysis and meta-regression of omega-3 PUFA supplementation for major depression.

Martins 2009 - EPA but not DHA appears to be responsible for the efficacy of omega-3 LC-PUFAsupplementation in depression: evidence from a meta-analysis of randomized controlled trials

Jazayeri et al 2008 - Therapeutic effects of omega-3 EPA and fluoxetine, separately and in combination, in major depression