title: Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.
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.
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: R J T
authors.initials: RJ
authors.lastname: Mocking
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Harmsen
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Assies
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: M W J
authors.initials: MW
authors.lastname: Koeter
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.|Department of Psychiatry, Mood and Anxiety Disorders, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Ruhé
authors.affiliation: Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Schene
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis
chemical_list: D000928:Antidepressive Agents; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid