Omega-3 Study Supports Adjunct Use To Treat Major Depressive Disorder

Omega-3 fatty acids may assist in the development of personalized treatment plans for major depression, as the oils were found to be especially beneficial if they contained high levels of EPA and were used by people on anti-depressants, Dutch researchers say in a meta-analysis.

A meta-analysis concludes that supplementation with omega-3 fatty acids could assist in the development of personalized treatment plans for depression and other neuropsychiatric disorders, according to a University of Amsterdam study.

“Omega-3 supplements may be specifically effective in the form of EPA in depressed patients using antidepressants,” said Roel Mocking, lead author and a researcher at the university's Department of Psychiatry Program for Mood Disorders, in a March 18 release.

The implications of the findings could be significant, given the incidence of depression, which affects an estimated 350m people globally. In 2014, the National Institutes of Mental Health estimated 15.7m adults in the US had at least one major depressive episode in the previous year.

However, Mocking calls for precision/personalized medicine trials to identify possible interactions between eicosapentaenoic acid and antidepressants, in order to “provide targets to improve antidepressants response and its prediction.”

Published in the journal Translational Psychiatry, the study evaluated 13 studies on a total of 1,233 participants and concluded that the standard mean difference in benefit for patients taking omega-3s over those not supplementing is 0.398. However, higher EPA dose and higher percentage antidepressant users were “significantly” associated with better outcomes.

The study found a combination of EPA plus docosahexaenoic acid had no significant effect, nor did DHA alone. However, DHA does not appear to counteract the effect of EPA, the researchers note.

Representing a revised updated meta-analysis, the study “adds nuance to the continuing debate on the effect of omega-3 PUFA supplementation on depressive symptoms in MDD,” Mocking and his colleagues say.

“By including a relatively homogenous group of patients with MDD according to DSM criteria as assessed using a standardized clinical interview, we aimed to enhance internal validity and generalizability of the present meta-analysis."

They add, though, that the subjects from the studies comprised a heterogeneous group, including participants who will benefit from omega-3 supplementation and those who experience no or negative effects.

Further, other unreported factors could influence study subjects' response to omega-3s and those could not be tested in the meta-analysis and meta-regression, such as measurements of inflammation or nutrigenetics.

The researchers note that over the last decade, several meta-analyses have shown varying degrees of beneficial effects of omega-3 fatty acids for MDD, but made “critical” remarks regarding the quality of the evidence and possible publication bias.

Studies also have provided mixed results on whether EPA can help depression. Some have indicated that supplementation benefits are situational, while another Dutch study published in 2011 found that omega-3s do not relieve depression in patients who have suffered a heart attack (Also see "Research & Development In Brief" - Pink Sheet, 19 Dec, 2011.).

RCTs With Adults

The researchers collected studies from a search in the Medline and Embase databases through Dec. 8, 2015, using a strategy combining terms regarding MDD and fatty acid supplementation.

Two independent reviewers screened the identified articles for relevance by title and abstract. In addition to randomized placebo-controlled trial design, the analysis included studies featuring adults with MDD according to the Diagnostic and Statistical Manual of Mental Disorders as assessed by a standardized clinical interview.

The researchers excluded studies that specifically studied perinatal or perimenopausal MDD or studies that looked at the condition secondary to other neuropsychiatric disorders.

They noted several limitations in the study, including that a meta-analysis has not been performed on patient data, which could “lead to additional predictors of supplementation outcome, giving rise to extra targets for future precision medicine studies.”

Further, while their study "had enough power to detect small-to-medium effect sizes, smaller regression effects may have been lost as a result of the smaller number of studies due to the specific in-and exclusion criterial,” they add.

“To maintain power for the meta-regression regarding the effect of percentage antidepressant users on supplementation outcome, we pooled all concurrent antidepressant classes together, while the effects may differ per class. It would be interesting to further test this in future studies including users of different antidepressants.”