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International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder

Guu TW, Mischoulon D, Sarris J, Hibbeln J, McNamara RK, Hamazaki K, Freeman MP, Maes M, Matsuoka YJ, Belmaker RH, Jacka F, Pariante C, Berk M, Marx W, Su KP (2019) Psychother Psychosom.  2019;88(5): 263-273. doi: 10.1159/000502652. 

Web URL: Read this and related abstracts on PubMed here, Free full text of this article is available via Open


Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely reported.

The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n-3 PUFAs in MDD.

The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues.

The key practice guidelines contend that:

(1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n-3 PUFAs in depression treatment;

(2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA >2) are considered effective, and the recommended dosages should be 1-2 g of net EPA daily, from either pure EPA or an EPA/DHA (>2:1) formula;

(3) the quality of n-3 PUFAs may affect therapeutic activity; and

(4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels.

The expert consensus panel has agreed on using n-3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations.

Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.


Clinical trial evidence that depressive symptoms can be reduced by dietary supplementation with omega-3 long-chain polyunsaturated fatty acids (found naturally in fish and seafood) has been accumulating now for many years. For a FAB comment detailing some of the key research studies in this area that have led to this much-needed consensus statement and guidelines for clinicians, please see the landmark study published almost 20 years ago by Professor Malcolm Peet and colleagues:

Systematic reviews and meta-analyses since then have shown that the anti-depressant effects of these omega-3:
(1) are attributable to EPA, rather than DHA
(2) are most evident in patients with clinical-level depressive symptoms (i.e. Major Depressive Disorder, or Bipolar Depression)
(3) may operate synergistically to enhance the effects of antidepressant medications - although they can also be effective as monotherapy

This new open-access review presents the current consensus from the world's leading researchers and clinicians in this area, summarising the evidence to date, and providing detailed treatment guidelines for clinicians.

Although the use of omega-3 supplements as an adjunctive treatment for depression (and for other psychiatric disorders) was first endorsed by the American Psychiatric Association in 2006, many clinicians still receive little or no professional training in this area.

This review, from members of the International Society for Nutrition in Psychiatry Research, therefore meets an important clinical need. It also provides useful information and guidance for anyone seeking evidence-based information on the potential value of omega-3 supplementation in the management of depressive symptoms.

See the associated news article:

And for more information on this subject, please see the following lists of news articles and research studies, which are regularly updated: