Food and Behaviour Research

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Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study

Frangou S, Lewis M, McCrone P (2006) Br J Psychiatry. 188 46-50. 

Web URL: View this and related abstracts via PubMed here. Free full text of this article is available online


BACKGROUND: Epidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid (EPA) alleviates unipolar depression.

AIMS: To examine the efficacy of EPA in treating depression in bipolar disorder.

METHOD: In a12-week, double-blind study individuals with bipolar depression were randomly assigned to adjunctive treatment with placebo (n=26) or with 1 g/day (n=24) or 2 g/day (n=25) of ethyl-EPA. Primary efficacy was assessed by the Hamilton Rating Scale for Depression (HRSD), with changes in the Young Mania Rating Scale and Clinical Global Impression Scale (CGI) as secondary outcome measures.

RESULTS: There was no apparent benefit of 2 g over 1 g ethyl-EPA daily. Significant improvement was noted with ethyl-EPA treatment compared with placebo in the HRSD (P=0.04) and the CGI (P=0.004) scores. Both doses were well tolerated.

CONCLUSIONS: Adjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression.


This clinical trial found that dietary supplementation with the omega-3 EPA alone - as an adjunct to standard treatment - was superior to placebo in reducing depressive symptoms in patients with bipolar disorder.

Similar benefits were found for doses of either 1g/day or 2/g day of EPA.  These two doses were tested because previous dose-ranging trials of adjunctive treatment with pure EPA have reported benefits for both depression and schizophrenia - with optimal responses in those conditions indicated as 1g/day and 2g/day respectively.

This study adds to existing clinical trial evidence that supplementation with the omega-3 long-chain polyunsaturated fatty acids found in fish oils (EPA and DHA) can reduce symptoms in patients wih psychiatric disorders including major depression, bipolar disorder, schizophrenia and ADHD.

Further research is still needed to confirm and extend these findings. 

Meanwhile, however, given the safety and tolerability of these omega-3, their known role as nutrients that are essential to general health as well as brain function, and the sub-optimal levels found in modern western-type diets, ensuring an adequate dietary intake of EPA/DHA either via food or supplementation makes sense - as recommended in recent treatment guidelines from the American Psychiatric Association. See:

For more information on this topic, please see also this list of studies, which is regularly updated: