Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials
Open accessAbstract
BACKGROUND: Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal. OBJECTIVES: To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies. METHODS: A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients. RESULTS: Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects. CONCLUSIONS: The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.
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Independent clinical trials and meta-analyses of RCTs have provided evidence of the superiority of n-3 polyunsaturated fatty acids, namely eicosapentaenoic and docosahexaenoic acids, over placebo as augmentation agents in the treatment of major depressive disorder.
“Independent clinical trials and meta-analyses of RCTs have also provided evidence of the superiority of n-3 PUFAs, namely eicosapentaenoic and docosahexaenoic acids, over a placebo as augmentation agents in the treatment of MDD [138].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [138]
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- Authors
- Grosso, G., Pajak, A., Marventano, S., Castellano, S., Galvano, F., Bucolo, C., Drago, F., & Caraci, F.
- Affiliations
- University of Catania (IT)
- Corresponding author
- Grosso, Giuseppe
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-05-07
- Volume
- 9
- Issue
- 5
- Pages
- e96905
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4013121
- OpenAlex
- W2047790936
- Cited by
- 449
- References
- 130
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 21 · 2023: 36 · 2022: 28 · 2021: 28 · 2020: 33 · 2019: 51 · 2018: 46 · 2017: 53 · 2016: 54 · 2015: 51 · 2014: 8
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- omega-3 fatty acids, polyunsaturated fatty acids, depression, major depressive disorder, eicosapentaenoic acid, docosahexaenoic acid, omega-3 supplementation, adjuvant therapy, bipolar disorder, perinatal depression, young adults, depression severity
- MeSH terms
- Depressive Disorder, Docosahexaenoic Acids, Female, Humans, Pregnancy, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Randomized Controlled Trials as Topic, MEDLINE, Dietary Supplements
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