EPA Omega-3 and Depression
EPA, or eicosapentaenoic acid, is a long-chain omega-3 fatty acid. Among nutrients studied in depression it carries the strongest guideline support: the 2022 WFSBP and CANMAT clinician guidelines give adjunctive omega-3 fatty acids their strongest rating for any nutrient in unipolar depression. Trials generally use formulations in which EPA predominates over DHA.
Why EPA is the figure to compare
EPA
DHA
What is EPA?
EPA is one of the two long-chain omega-3 fatty acids found in oily fish, the other being docosahexaenoic acid, or DHA. The body can make only small amounts from the shorter-chain omega-3 found in plants, so intake comes largely from diet. Both are present in fish oil, but in differing proportions depending on the source and the processing, which is why the EPA content of a product matters more than its total omega-3 content.
What has the research found?
The 2022 clinician guidelines from the World Federation of Societies of Biological Psychiatry and the Canadian Network for Mood and Anxiety Treatments give adjunctive omega-3 fatty acids their strongest rating for any nutrient in unipolar depression. [1] A systematic review and meta-analyses in the American Journal of Psychiatry pooled the adjunctive omega-3 trials and found a significant, moderate to strong effect in favour of omega-3 over placebo, with an effect size of 0.61 (95% CI 0.15 to 1.06, p = 0.009). [2] A 2023 systematic review and meta-analysis of randomised controlled trials examined long-chain omega-3 fatty acids for reducing depression and anxiety in adults. [3] The International Society for Nutritional Psychiatry Research published dedicated practice guidelines for omega-3 fatty acids in major depressive disorder in 2019. [4] And a meta-review of thirty-three meta-analyses covering 10,951 people, published in World Psychiatry, names eicosapentaenoic acid specifically as the nutrient carrying the strongest evidence in depression. [5]
Why EPA rather than DHA?
The trials that have found benefit have generally used formulations in which EPA makes up the majority of the omega-3 content. The American Journal of Psychiatry review found primarily positive results in replicated studies for omega-3, naming EPA or ethyl-EPA specifically. [2] A 2019 meta-analysis in Translational Psychiatry examined this proportion directly across the trial literature. [6] This is why a product’s EPA figure is the one worth comparing, and why total omega-3 content on its own can be misleading, since two products with the same total can differ substantially in how much of it is EPA.
What dose has been studied?
Across the adjunctive trials reviewed in the American Journal of Psychiatry, EPA ranged from 930 mg to 4.4 g a day, with the review describing 1 to 2 g a day as a therapeutic dose. [2] The ISNPR practice guidelines and the WFSBP and CANMAT guidelines set out the doses they assessed. [1][4] Anyone comparing products should look at milligrams of EPA per day rather than capsule count or total oil content, since neither of those indicates how much EPA is actually delivered.
Where Hedonia sits
Four Hedonia capsules a day provide 1,440 mg of EPA, from 1,800 mg of omega-3 triglycerides, which sits within the 1 to 2 g daily band the American Journal of Psychiatry review describes as a therapeutic dose. Alongside it, four capsules provide 15 mg of L-methylfolate and 1,200 mg of SAMe. Hedonia is a medical food for the dietary management of the nutritional requirements associated with depression, intended for use under medical supervision alongside a physician-directed treatment plan.
References
- Sarris J, Ravindran A, Yatham LN, Marx W, Rucklidge JJ, McIntyre RS, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: the WFSBP and CANMAT Taskforce. World J Biol Psychiatry. 2022;23(6):424-455. PMID 35311615. PubMed
- Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, Ng CH. Adjunctive nutraceuticals for depression: a systematic review and meta-analyses. Am J Psychiatry. 2016;173(6):575-587. PMID 27113121. PubMed
- Kelaiditis CF, Gibson EL, Dyall SC. Effects of long-chain omega-3 polyunsaturated fatty acids on reducing anxiety and/or depression in adults: a systematic review and meta-analysis of randomised controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2023;192:102572. PMID 37028202. PubMed
- Guu TW, Mischoulon D, Sarris J, Hibbeln J, McNamara RK, Hamazaki K, et al. International Society for Nutritional Psychiatry Research practice guidelines for omega-3 fatty acids in the treatment of major depressive disorder. Psychother Psychosom. 2019;88(5):263-273. PMID 31480057. PubMed
- Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, et al. The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry. 2019;18(3):308-324. Open access
- Liao Y, Xie B, Zhang H, He Q, Guo L, Subramanieapillai M, et al. Efficacy of omega-3 PUFAs in depression: a meta-analysis. Transl Psychiatry. 2019;9(1):190. PMID 31383846. PubMed