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Cited by 449Fatty Acid Research and HealthTreatment of Major DepressionTryptophan and brain disorders

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Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

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Grosso, Giuseppe, Pajak, Andrzej, Marventano, Stefano, Castellano, Sabrina, Galvano, Fabio, Bucolo, Claudio, Drago, Filippo, Caraci, Filippo·2014·PLoS ONE
DOI 10.1371/journal.pone.0096905PMC PMC4013121
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Abstract

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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Figure 1 Process of inclusion of trials for systematic review and meta-analysis of studies on omega-3 fatty acids and depressive symptoms.
Figure 1 Process of inclusion of trials for systematic review and meta-analysis of studies on omega-3 fatty acids and depressive symptoms.CC BY · PubMed Central
Figure 2 Forest plot showing individual and combined effect size estimates and 95% CIs for 19 trials grouped in those conducted on patients with a DSM-defined diagnosis of major depressive disorder (MDD group, n = 11) and those on patients with an assessment of depression but not rigorously diagnosed according to the DSM criteria (non-MDD group, n = 8). Black squares: indicate the weighting given to the trial in the overall pooled estimate; lines: indicate the 95% CIs; rhombus: indicate the combined effect size.
Figure 2 Forest plot showing individual and combined effect size estimates and 95% CIs for 19 trials grouped in those conducted on patients with a DSM-defined diagnosis of major depressive disorder (MDD group, n = 11) and those on patients with an assessment of depression but not rigorously diagnosed according to the DSM criteria (non-MDD group, n = 8). Black squares: indicate the weighting given to the trial in the overall pooled estimate; lines: indicate the 95% CIs; rhombus: indicate the combined effect size.CC BY · PubMed Central
Figure 3 Funnel plot of effect size estimates for individual trials conducted on patients with depressive disorder without secondary comordibities (MDD group and non-MDD group, n = 19).
Figure 3 Funnel plot of effect size estimates for individual trials conducted on patients with depressive disorder without secondary comordibities (MDD group and non-MDD group, n = 19).CC BY · PubMed Central
Figure 4 Forest plot examining the effect of the type of omega-3 PUFA supplementation employed on the reduction in depressive symptoms (MDD group and non-MDD group, n = 19).
Figure 4 Forest plot examining the effect of the type of omega-3 PUFA supplementation employed on the reduction in depressive symptoms (MDD group and non-MDD group, n = 19).CC BY · PubMed Central
Figure 5 Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on patients with bipolar depression.
Figure 5 Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on patients with bipolar depression.CC BY · PubMed Central
Figure 6 Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on pregnant women with major depressive disorder.
Figure 6 Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on pregnant women with major depressive disorder.CC BY · PubMed Central
Figure 7 Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on healthy pregnant women for prevention of post-partum depression.
Figure 7 Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on healthy pregnant women for prevention of post-partum depression.CC BY · PubMed Central
Figure 8 Forest plot showing individual and combined effect size estimates and 95% CIs for 2 trials conducted on patients with Alzheimer or mild cognitive impairment.
Figure 8 Forest plot showing individual and combined effect size estimates and 95% CIs for 2 trials conducted on patients with Alzheimer or mild cognitive impairment.CC BY · PubMed Central
Figure 9 Forest plot showing individual and combined effect size estimates and 95% CIs for 2 trials conducted on patients with schizophrenia.
Figure 9 Forest plot showing individual and combined effect size estimates and 95% CIs for 2 trials conducted on patients with schizophrenia.CC BY · PubMed Central
Figure 10 Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on patients with cardiovascular disease.
Figure 10 Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on patients with cardiovascular disease.CC BY · PubMed Central
Figure 11 Forest plot showing individual and combined effect size estimates and 95% CIs for 6 trials conducted on healthy individuals for prevention of depressive symptoms.
Figure 11 Forest plot showing individual and combined effect size estimates and 95% CIs for 6 trials conducted on healthy individuals for prevention of depressive symptoms.CC BY · PubMed Central

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Metadata

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)
DOI
10.1371/journal.pone.0096905
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
Licence
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 (medical) › 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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