Food and Behaviour Research

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Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression

Hallahan B, Ryan T, Hibbeln JR, Murray IT, Glynn S, Ramsden CE, SanGiovanni JP, Davis JM. (2016) Br J Psychiatry. 209(3): 192-201 Epub 2016, Apr 21. doi: 10.1192/bjp.bp.114.160242. 

Web URL: View this and related abstracts via PubMed here.



Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings.


To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials.


A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo.


Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge's G= 0.61, P<0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression.


Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.

© The Royal College of Psychiatrists 2016.


This new systematic review and meta-analysis extends and confirms the pattern of findings shown in previous studies of long-chain omega-3 fatty acids for depression, i.e. that EPA-rich formulations are effective in patients with clinically diagnosed depression.

Ordinary fish oils contain both EPA and DHA (usually with slightly more EPA) - but although supplements richer in DHA have been established as beneficial for some purposes (e.g. during pregnancy, for reducing prematurity and supporting brain development; and for vision and cognition at all ages), they do NOT appear to be effective for depression.

  • Omega-3 DHA plays a key structural role in brain and nerve cells (as an essential component of cell membranes), as well as many functional, cell signalling roles.
  • Omega-3 EPA plays little or no structural role - but it plays a huge variety of functional roles via its many derivatives - influencing hormonal balance, blood flow and immune function as well as any other aspects of cell signalling.
The superiority of EPA over DHA with respect to antidepressant actions has been consistently apparent since the earliest studies - so it is to be hoped that this latest meta-analysis - and another with similar conclusions - will help clarify this issue, and be used to inform future trial designs.

Another important finding is that EPA is effective as an adjunctive treatment - and therefore benefit to the many patients who still have clinical-level systoms despite the best pharmcological interventions.

There is some evidence to indicate that EPA may even act 'synergistically' with standard antipressant medication such as SSRIs to enhance their effects - although further research on this is still required.

See also:

And for more information on omega-3 and depression, please see the following lists, which are regularly updated.