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Meta-Analysis
. 2014 May 7;9(5):e96905.
doi: 10.1371/journal.pone.0096905. eCollection 2014.

Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials

Giuseppe Grosso  1 , Andrzej Pajak  2 , Stefano Marventano  3 , Sabrina Castellano  1 , Fabio Galvano  1 , Claudio Bucolo  1 , Filippo Drago  1 , Filippo Caraci  4
Affiliations
Meta-Analysis

Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials

Giuseppe Grosso et al. PLoS One. .

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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Process of inclusion of trials for systematic review and meta-analysis of studies on omega-3 fatty acids and depressive symptoms.
Figure 2
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 3
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 4
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 5
Figure 5. Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on patients with bipolar depression.
Figure 6
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 7
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 8
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 9
Figure 9. Forest plot showing individual and combined effect size estimates and 95% CIs for 2 trials conducted on patients with schizophrenia.
Figure 10
Figure 10. Forest plot showing individual and combined effect size estimates and 95% CIs for 3 trials conducted on patients with cardiovascular disease.
Figure 11
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.
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Publication types

Grants and funding

Giuseppe Grosso and Sabrina Castellano were supported by the International Ph.D. Program in Neuropharmacology, University of Catania, Catania, Italy. The contributors had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.