High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis

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Abstract

Background

The application of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) supplementation for major depressive disorder (MDD) has been widely discussed in recent years, but its efficacy and application are still controversial. This network meta-analysis was conducted to compare the efficacy of different dosages of n-3 PUFAs on MDD patients in the early period of treatment.

Methods

Randomized controlled trials (RCTs) exploring the efficacy of n-3 PUFA supplementation for patients with MDD were retrieved from the databases of Pubmed, Embase and the Cochrane Library. RCTs comparing the efficacy of n-3 PUFA for adult (≥18 years) MDD patients without comorbidity were eligible for our study. The score of depressive symptoms in early therapy period of the treatment (≤9 weeks) was extracted. Standardized mean deviations (SMDs) of all the sores from the eligible RCTs were synthesized in a pairwise meta-analysis in frequentist framework and a random-effects network meta-analysis in Bayesian framework for the overall and subgroups (high- and low-dose) efficacy of n-3 PUFAs.

Results

A total of 910 MDD patients in 10 trials with 3 adjuvant therapy strategies (high-dose n-3 PUFAs, low-dose n-3 PUFAs and placebo) were included. Results of pairwise meta-analysis showed that n-3 PUFAs were superior to placebo (SMD: 1.243 ± 0.596; 95% CI: 0.060 ~ 2.414). Results of the network meta-analysis showed that both the high (SMD: 0.908 ± 0.331; 95% CI: 0.262 ~ 1.581) and the low-dose (SMD: 0.601 ± 0.286; 95% CI: 0.034 ~ 1.18) n-3 PUFAs were superior to placebo, and the efficacy of high-dose n-3 PUFAs is superior to that of low-dose.

Conclusions

High-dose n-3 PUFAs supplementation might be more superior than low-dose in the early therapy period for MDD. More head-to-head clinical trials need to be carried out to provide more direct comparison and enhance the evidence of the efficacy of n-3PUFAs for MDD.

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Most cited references 37

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Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression.

Amy L Geant, Graham Mann, Hayley Ellis … (2011)

Randomized trials of omega-3 polyunsaturated fatty acid (PUFA) treatment for depression have differed in outcome. Recent meta-analyses ascribe discrepancies to differential effects of eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) and to diagnostic heterogeneity. This meta-analysis tests the hypothesis that EPA is the effective component in PUFA treatment of major depressive episodes. PubMed/MeSH was searched for studies published in English from 1960 through June 2010 using the terms fish oils (MeSH) AND (depressive disorder [MeSH] OR bipolar depression) AND randomized controlled trial (publication type). The search was supplemented by manual bibliography review and examination of relevant review articles. The search yielded 15 trials involving 916 participants. Studies were included if they had a prospective, randomized, double-blinded, placebo-controlled study design; if depressive episode was the primary complaint (with or without comorbid medical conditions); if omega-3 PUFA supplements were administered; and if appropriate outcome measures were used to assess depressed mood. Extracted data included study design, sample sizes, doses and percentages of EPA and DHA, mean ages, baseline and endpoint depression ratings and standard deviations for PUFA and placebo groups, and P values. The clinical outcome of interest was the standardized mean difference in the change from baseline to endpoint scores on a depression rating scale in subjects taking PUFA supplements versus subjects taking placebo. In a mixed-effect model, percentage of EPA in the supplements was the fixed-effect predictor, dichotomized into 2 groups: EPA < 60% or EPA ≥ 60% of the total EPA + DHA. Secondary analyses explored the relevance of treatment duration, age, and EPA dose. Supplements with EPA ≥ 60% showed benefit on standardized mean depression scores (effect size = 0.532; 95% CI, 0.277-0.733; t = 4.195; P < .001) versus supplements with EPA < 60% (effect size = -0.026; 95% CI, -0.200 to 0.148; t = -0.316; P = .756), with negligible contribution of random effects or heteroscedasticity and with no effects of treatment duration or age. Supplements with EPA < 60% were ineffective. Exploratory analyses supported a nonlinear model, with improvement determined by the dose of EPA in excess of DHA, within the range of 200 to 2,200 mg/d of EPA. Supplements containing EPA ≥ 60% of total EPA + DHA, in a dose range of 200 to 2,200 mg/d of EPA in excess of DHA, were effective against primary depression. Translational studies are needed to determine the mechanisms of EPA's therapeutic benefit. © Copyright 2011 Physicians Postgraduate Press, Inc.

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Omega-3 Fatty Acids for the Treatment of Depression: Systematic Review and Meta-Analysis

Michael Bloch, Jonas Hannestad (2011)

We conducted a meta-analysis of randomized, placebo-controlled trials of omega-3 fatty acid treatment of major depressive disorder in order to determine efficacy and to examine sources of heterogeneity between trials. PubMED (1965-May 2010) was searched for randomized, placebo-controlled trials of omega-3 fatty acids for major depressive disorder. Our primary outcome measure was standardized mean difference in a clinical measure of depression severity. In stratified meta-analysis we examined the effects of trial duration, trial methodological quality, baseline depression severity, diagnostic indication, dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in omega-3 preparations, and whether omega-3 fatty acid was given as monotherapy or augmentation. In 13 randomized, placebo-controlled trials examining the efficacy of omega-3 fatty acids involving 731 participants, meta-analysis demonstrated no significant benefit of omega-3 fatty acid treatment compared to placebo (SMD=0.11, 95% CI: -0.04, 0.26). Meta-analysis demonstrated significant heterogeneity and publication bias. Nearly all evidence of omega-3 benefit was removed after adjusting for publication bias using the trim-and-fill method (SMD=0.01, 95% CI: -0.13, 0.15). Secondary analyses suggested a trend towards increased efficacy of omega-3 fatty acids in trials of lower methodological quality, trials of shorter duration, trials, which utilized completers rather than intention-to-treat analysis, and trials in which study participants had greater baseline depression severity, Current published trials suggest a small, non-significant benefit of omega-3 fatty acids for major depression. Nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias.

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A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs.

D. Horrobin, Malcolm Peet (2002)

In depressed patients, low blood levels of eicosapentaenoic acid are seen. We tested the antidepressive effect of ethyl-eicosapentaenoate in these patients. We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a standard antidepressant. Patients were randomized on a double-blind basis to placebo or ethyl-eicosapentaenoate at dosages of 1, 2, or 4 g/d for 12 weeks in addition to unchanged background medication. Patients underwent assessment using the 17-item Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, and the Beck Depression Inventory. Forty-six (88%) of 52 patients receiving ethyl-eicosapentaenoate and 14 (78%) of 18 patients receiving placebo completed the 12-week study with no serious adverse events. The 1-g/d group showed a significantly better outcome than the placebo group on all 3 rating scales. In the intention-to-treat group, 5 (29%) of 17 patients receiving placebo and 9 (53%) of 17 patients receiving 1 g/d of ethyl-eicosapentaenoate achieved a 50% reduction on the Hamilton Depression Rating Scale score. In the per-protocol group, the corresponding figures were 3 (25%) of 12 patients for placebo and 9 (69%) of 13 patients for the 1-g/d group. The 2-g/d group showed little evidence of efficacy, whereas the 4-g/d group showed nonsignificant trends toward improvement. All of the individual items on all 3 rating scales improved with the 1-g/d dosage of ethyl-eicosapentaenoate vs placebo, with strong beneficial effects on items rating depression, anxiety, sleep, lassitude, libido, and suicidality. Treatment with ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in treating depression in patients who remained depressed despite adequate standard therapy.

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Author and article information

Contributors

Ji-yang Pan: jiypan@163.com

Journal

Journal ID (nlm-ta): BMC Psychiatry

Journal ID (iso-abbrev): BMC Psychiatry

Title: BMC Psychiatry

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-244X

Publication date (Electronic): 20 May 2020

Publication date PMC-release: 20 May 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 248

Affiliations

[1 ]GRID grid.412601.0, ISNI 0000 0004 1760 3828, Department of Psychiatry, , The First Affiliated Hospital, Jinan University, ; Guangzhou, 510630 China

[2 ]GRID grid.410560.6, ISNI 0000 0004 1760 3078, Department of Psychiatry, , Affiliated Hospital of Guangdong Medical University, ; Zhanjiang, 524001 China

[3 ]GRID grid.410560.6, ISNI 0000 0004 1760 3078, Marine Medicine Research Institute, , Guangdong Medical University, ; Zhanjiang, 524023 China

[4 ]GRID grid.268099.c, ISNI 0000 0001 0348 3990, Institute of Lipids Medicine and School of Public Health, , Wenzhou Medical University, ; Wenzhou, 325035 China

[5 ]GRID grid.411508.9, ISNI 0000 0004 0572 9415, Department of Psychiatry, , China Medical University Hospital, ; Taichung, 400 Taiwan

Article

Publisher ID: 2656

DOI: 10.1186/s12888-020-02656-3

PMC ID: 7238659

PubMed ID: 32434488

SO-VID: 4b72b3f0-3cb6-4103-85dc-ee9d25bbde0d

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 7 March 2019

Date accepted : 11 May 2020

Funding

Funded by: Natural Science Foundation of Guangdong Province (CN)

Award ID: 2017A030313648

Award Recipient : Ji-yang Pan

Custom metadata

ScienceOpen disciplines: Clinical Psychology & Psychiatry

Keywords: omega-3,polyunsaturated fatty acid,supplementation,major depressive disorder,network meta-analysis

Data availability:

ScienceOpen disciplines: Clinical Psychology & Psychiatry

Keywords: omega-3, polyunsaturated fatty acid, supplementation, major depressive disorder, network meta-analysis

High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis

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Abstract

Background

Methods

Results

Conclusions

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Most cited references 37

Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression.

Omega-3 Fatty Acids for the Treatment of Depression: Systematic Review and Meta-Analysis

A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs.

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