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 (I2=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.
Highlights
Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed as a treatment for major depressive disorder (MDD)
Several meta-analyses have been performed, which suggested variable degrees of beneficial effects of omega-3 PUFAs for MDD, but made critical remarks regarding the quality of the evidence and possible publication bias.[1,2,3,4,5,6]
PUFAs were effective in depressive patients with or without an MDD diagnosis; (2) Yang et al.[10] pooled randomized controlled trials (RCTs) published up to
Summary
Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed as a treatment for major depressive disorder (MDD). Several meta-analyses have been performed, which suggested variable degrees of beneficial effects of omega-3 PUFAs for MDD, but made critical remarks regarding the quality of the evidence and possible publication bias.[1,2,3,4,5,6] These metaanalyses evoked academic correspondence, discussing the used inclusion criteria and selection of outcome measures.[7,8] In brief, this correspondence suggested beneficial effects (1) if a higher ratio of omega-3 PUFA eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) was being supplemented[7] and (2) only in patients with actual MDD as opposed to subjects with merely depressive symptoms.[8] Of these meta-analyses, only the three most recent metaanalyses covered the research performed over the last 5 years: (1) Grosso et al.[9] included randomized controlled trials (RCTs) published up to August 2013, and concluded that omega-3. Grosso et al and Yang et al included three articles that all seem to report on the same RCT,[13,14,15] that is, (partial) duplicate publication which distorts pooled-effect
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