Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial

Okereke OI, et al

Published in JAMA

Methodology

Randomised, double-blind, placebo-controlled 2x2 factorial ancillary study to VITAL (NCT01696435, NCT01169259); 9,171 assigned to 1 g/day marine omega-3 and 9,182 to matching placebo, randomised November 2011 to March 2014 with treatment ending 31 December 2017; coprimary outcomes were incident plus recurrent depression or clinically relevant depressive symptoms and mean change in the PHQ-8 mood score; 90.3% completed.

Key Findings

VITAL-DEP randomised 18,353 US adults aged 50 and over (mean age 67.5, 49.2% women) to 1 g/day marine omega-3 (465 mg EPA plus 375 mg DHA) or placebo for a median of 5.3 years. Depression or clinically relevant depressive symptoms were slightly more common on omega-3 (651 events, 13.9 per 1000 person-years) than placebo (583 events, 12.3 per 1000 person-years; HR 1.13, 95% CI 1.01-1.26, p = 0.03). Mood scores showed no difference: mean change in PHQ-8 differed by just 0.03 points (95% CI -0.01 to 0.07, p = 0.19). Serious adverse events, cardiovascular events, mortality and bleeding were comparable between groups. The authors state these findings do not support omega-3 supplements for preventing depression.

Conclusions

These findings do not support the use of omega-3 supplements in adults to prevent depression.

Limitations

Participants were aged 50 and over and free of clinically relevant depressive symptoms at baseline, so results do not apply to treating existing depression or to younger adults; only one dose was tested and the small increase in risk sits close to the boundary of statistical significance.