Two independent, trained reviewers screened the identified articles for their relevance by title/abstract and full text. We also searched the references of selected studies and earlier meta-analyses to identify additional potential studies for inclusion in our analysis. We applied our search in the following databases, from inception to 20 December 2017: PubMed and the Ovid version of EMBASE (Supplementary 1). We conducted a systematic bibliographic search for studies that examined the role of omega-3 PUFAs in depression using “major depressive disorder”, “depression”, “fatty acid, omega-3”, and “randomized controlled trial” as key words.
Therefore, we conducted this meta-analysis to provide an update on the therapeutic effect of omega-3 PUFAs and on the associations between EPA or DHA supplementation and depression, including the effects of the dosage and proportion of EPA or DHA supplementation on depression. However, whether and how EPA and DHA initiate their effects on depression differentially or synergistically with regard to dosage and proportion are still unclear. Given the discrepancy in these methodological aspects, the results would be interpreted differently in each of the previously mentioned studies.
also reported that compared to 4 g/d, greater efficacy was found at 1 g/d and 2 g/d in a single-arm randomized trial on depression 5.
Regarding DHA supplementation, Mischoulon et al. Recent double-blinded randomized controlled trials (RCTs) indicated that EPA, mostly at dosages of 1 or 2 g/d, was better (than placebo and DHA) as a monotherapy or adjuvant in the treatment of mild to moderate depression and that the ratio of an ‘active’ synergetic effect between EPA and DHA would probably be either 2:1 or 3:1 10, 11, 12.
Some studies have also demonstrated that different dosages of EPA and DHA may result in different levels of efficacy. Previous meta-analyses have proposed that PUFAs that are mainly EPA (EPA > 50% 7, 60% 8, and 80% 9 of the dose) have significantly greater efficacy than those that are mainly DHA (DHA > 50%, 60%, and 80% of the dose, respectively), regardless of PUFAs monotherapy or adjuvant use. The treatment efficacy of supplementation with omega-3 PUFAs in depression is influenced by the proportion and dosage of EPA or DHA. The different therapeutic effects of EPA and DHA on depression need to be further studied. However, EPA and DHA may play different roles in depression because of their involvement in anti-inflammatory activity and their maintenance of membrane integrity and fluidity, respectively 6. Supplementation with the two main types of omega-3 PUFAs, eicosapentaenoic acid (EPA) 3, and docosahexaenoic acid (DHA) 4, 5, has also been found to be effective in reducing symptoms of depression. Further studies are warranted to examine supplementation with omega-3 PUFAs for specific subgroups of subjects with inflammation, severity of depression, and the dose response for both EPA and DHA supplementation.Ī growing body of evidence has indicated that omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been effective in improving depression 1, 2. Compared with placebo, EPA-pure (=100% EPA) and EPA-major formulations (≥60% EPA) demonstrated clinical benefits with an EPA dosage ≤1 g/d (SMD = −0.50, P = 0.003, and SMD = −1.03, P = 0.03, respectively), whereas DHA-pure and DHA-major formulations did not exhibit such benefits.Ĭurrent evidence supports the finding that omega-3 PUFAs with EPA ≥ 60% at a dosage of ≤1 g/d would have beneficial effects on depression.
The meta-analysis showed an overall beneficial effect of omega-3 polyunsaturated fatty acids on depression symptoms (SMD = −0.28, P = 0.004). Our search resulted in 180 articles we analyzed 26 studies, which included 2160 participants. A sensitivity analysis was also conducted to evaluate the stability of the results, and publication bias was evaluated by a funnel plot and Egger’s linear regression analysis. This meta-analysis was performed using RevMan 5.3 and R 3.4.3, and means and standard deviations were calculated in fixed- or random-effects models based on the results of the Q-test. We applied a systematic bibliographic search in PubMed and EMBASE for articles published prior to 20 December 2017. We conducted this meta-analysis of double-blind randomized placebo-controlled trials to estimate the efficacy of omega-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in the improvement of depression.