Omega-3 Fatty Acids for Major Depressive Disorder: A Systematic Review (original) (raw)

2015, RAND Corporation eBooks

Major depressive disorder (MDD) is a prevalent condition that accounts for considerable suffering and lost productivity. Epidemiological evidence supports a potential role for dietary and/or supplemental omega-3 (n-3) fatty acids in the management of depression. We conducted a systematic review of randomized controlled trials (RCTs) that assessed the efficacy and safety of n-3 fatty acids for treating depression. We searched the electronic databases PubMed, PsycINFO, CINAHL, Embase, and AMED and screened recent existing reviews to identify English-language reports of randomized placebo-controlled or head-to-head trials testing the efficacy and safety of n-3 fatty acids as a monotherapy or adjunctive therapy to treat adults with MDD. Standard systematic review methods were used to screen the literature against a predetermined set of inclusion and exclusion criteria, abstract the study-level details and outcomes of interest, and assess the methodological quality of the studies. Effectiveness outcomes were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The quality of evidence for each conclusion was assessed using the GRADE approach. We identified 24 RCTs that met inclusion criteria; 20 studies reported efficacy outcomes for placebo comparisons. All studies combined showed a small but significant effect of n-3 fatty acids compared with placebo on depression scale scores (standardized mean difference [SMD] 0.42; 95% confidence interval [CI] 0.11, 0.73; 20 RCTs; I2 77%; low quality of evidence) and on the proportion of treatment responders (odds ratio [OR] 2.09; CI 1.25, 3.49; 13 RCTs; I2 38% moderate quality of evidence), but there was evidence of publication bias. No statistically significant effect was found for the proportion of patients in remission compared with placebo (OR 2.19; CI 0.74, 6.51; 6 RCTs; I2 52%; low quality of evidence). Benefits compared with placebo were primarily based on monotherapy studies. Only two studies compared eicosapentaenoic acid (EPA) with docosahexaenoic acid (DHA) head to head. Pooling studies of EPA alone with high EPA:DHA ratio studies revealed a significant effect on depression scale scores (SMD 0.62; CI 0.25, 0.98; 15 RCTs; I2 77%; low quality of evidence) and on the proportion of treatment responders (OR 2.31; CI 1.09, 4.88; I2 51%; low quality of evidence) compared with placebo, but studies that administered DHA or a high DHA:EPA ratio showed no effect (SMD ???0.06; CI ???0.61, 0.49; 6 RCTs; I2 68%; moderate quality of evidence). Very few studies specified depression severity. Few studies assessed effects on quality of life. N-3 fatty acids were associated with an increased risk for mild gastrointestinal symptoms compared with placebo (OR 2.58; CI 1.73, 3.91; 17 RCTs; moderate quality of evidence) but not with other categories of minor adverse events or serious adverse events. In conclusion, the n-3 fatty acid EPA may