Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder
Mocking RJ, Harmsen I, Assies J, Koeter MW, Ruhé HG, Schene AH. (2016) Transl Psychiatry. 6 e756. doi: 10.1038/tp.2016.29.
Web URL: View this and related abstracts via PubMed here. Free full text of this article is available online
Abstract:
Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD).In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality.
To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model).
As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (β=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed.
In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants.
Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.
FAB RESEARCH COMMENT:
For a summary of this research study, see the associated news article:The superiority of EPA over DHA in reducing symptoms of depression found in this new analysis has been evident for some time, as have stronger treatment effects in patients with clinically diagnosed depression - where the effects of EPA appear comparable to those of standard antidepressant medications.
Importantly, these findings also support other studies indicating that EPA may be most effective when taken together with antidepressant medication. See for example:
- Hallahan et al 2016 - Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression
- Martins 2009 - EPA but not DHA appears to be responsible for the efficacy of omega-3 LC-PUFAsupplementation in depression: evidence from a meta-analysis of randomized controlled trials
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Richardson 2008 - n-3 Fatty acids and mood: the devil is in the detail
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