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 

Web URL: View this and related abstracts via PubMed here. Free Full Text of this paper is available online


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.



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 adjunctive treatment for depression.

Many such clinical trials have been conducted since, with a clear consensus emerging from systematic reviews that either EPA alone (but not DHA alone) - or fish oils that provide predominantly EPA rather than DHA, can indeed reduce depressive symptoms in patients with clinical depression.

There are also indications that the beneficial effects of EPA may be greater in patients taking standard antidepressant medications. However, further research is still needed to clarify whether this may reflect synergistic effects between the two, or simply a greater severity of depression in such patients.

In 2019, detailed, evidence-based guidelines for clinicians were published, alongside a summary of research, by a team of the world's leading researchers and clinicians in this area. Free full text of this article is available online - see:

and the related news article:

Just some of the news articles and key studies in this area include:

And for more news articles and research studies in this area, please see the following lists, which are regularly updated: