Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression

Abstract

Background: Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings.

Aims: To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials.

Method: A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo.

Results: Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge's G = 0.61, P<0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression.

Conclusions: Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.

Fig. 1. Flow chart of literature search and study selection.

EPDS, Edinburgh Post-Natal Depression Scale.

Fig. 2. Tree diagram.

When a group’s effect size (G) or number of strata (s) approaches zero no further analysis occurs. The width of the blue line is proportional to the number of trials in the following group. The area of the box under a group is proportional to its effect size. The grey boxes contain groups hypothesised to decrease effect size and the blue boxes contain groups hypothesised to increase effect size. Two strata had neither docosahexaenoic acid (DHA) nor eicosapentaenoic acid (EPA, n = 1365).

Fig. 3. Forest plot.

Size of blue squares proportional to weight in meta-analysis. Size of diamonds proportional to standard error of group. Black lines, show confidence intervals. The blue text indicates that a study was split into multiple strata and the criteria used to do so. H1/3* is the strata with the highest tertile of baseline depression scores; L2/3* is the strata with the lowest two teriles of baseline depression scores. ALA, α-linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; MDE, major depressive episode; Aug, augmentation; Mono, monotherapy.

Fig. 4. (a) Effect size in diagnosed and non-diagnosed studies; (b) funnel plot of standard error by effect size in eicosapentaenoic acid (EPA), diagnosed group.

In (a) each white dot represents one study and its effect size; the blue line represents the median effect size for the group and the grey line goes across the zero point (no difference between drug and placebo). In (b) each white dot represents a real study; each blue dot represents an imputed study; the white diamond indicates the calculated effect size, extending left and right to show 95% confidence intervals; the blue diamond indicates the imputed effect size, extending left and right to show 95% confidence intervals; the blue triangle outlines the ‘funnel’, centred at the imputed effect size and the blue vertical line extends upward, centred at the imputed effect size.