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Meta-Analysis
. 2024 Nov 20;11(11):CD014803.
doi: 10.1002/14651858.CD014803.pub2.

Omega-3 fatty acid supplementation for depression in children and adolescents

Susan C Campisi  1   2 , Clare Zasowski  3 , Glyneva Bradley-Ridout  4 , Anett Schumacher  1 , Peter Szatmari  1   3   5 , Daphne Korczak  1   6
Affiliations
Meta-Analysis

Omega-3 fatty acid supplementation for depression in children and adolescents

Susan C Campisi et al. Cochrane Database Syst Rev. .

Abstract

Background: Mental health disorders including major depressive disorder (MDD) are well recognized as major contributors to the global burden of disease among adolescents. The prevalence of adolescent depression is estimated to have increased by at least 25% during the COVID-19 pandemic, compounding the already challenging problem of insufficient mental health service and service accessibility that existed prepandemic. Omega-3 polyunsaturated fatty acid (PUFA) supplementation is currently recommended as a preventive treatment for depression in high-risk adults as well as a second-line monotherapy for adults with mild to moderate MDD, and adjunctive to antidepressants for adults with moderate to severe MDD. The benefits of omega-3 PUFA intake on depressive illness have been hypothesized to occur as a result of their effect on neurotransmission, maintenance of membrane fluidity, and anti-inflammatory action. A comprehensive synthesis and quantification of the existing evidence on omega-3 PUFA's efficacy in treating depression among children and adolescents is essential for clinicians to provide informed guidance to young people and their families, especially considering the absence of current guidelines for this age group.

Objectives: Primary objective To determine the impact of omega-3 PUFA supplementation versus a comparator (e.g. placebo, wait list controls, no treatment/supplementation, or standard care) on clinician-diagnosed depression or self-reported depression symptoms in children and adolescents. Secondary objectives To estimate the size of the effect of omega-3 PUFAs on depression symptoms. To estimate the effect of each type of omega-3 PUFA (EPA or DHA), compared with placebo, on depression. To determine if the effect is modified by dosage, format (capsule or liquid), sex, or age. To determine compliance and attrition for omega-3 PUFAs as an intervention for depression in children and adolescents. To determine the safety of omega-3 PUFAs as an intervention for depression in children and adolescents.

Search methods: We searched CENTRAL, MEDLINE, Embase, three other databases, reference lists of included studies, grey literature, and relevant reviews. The latest search date was 18 May 2023.

Selection criteria: We included randomized controlled trials (RCTs) involving males and females aged 19 years or younger with diagnosed depression comparing omega-3 PUFA supplementation to placebo, wait list control, no treatment/supplementation, or standard care.

Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were self-reported depression symptoms and clinically diagnosed resolution of depression. Our secondary outcomes were attrition, adverse effects, and compliance with the intervention. We used GRADE to assess the certainty of evidence for key outcomes.

Main results: We included five trials with 228 participants in our meta-analysis. All trials used a placebo comparator; intervention duration ranged from 10 to 16 weeks (median: 12 weeks). Omega-3 PUFA supplementation compared to placebo may reduce self-reported depression symptoms, but the evidence is very uncertain (standardized mean difference [SMD] -0.34, 95% confidence interval [CI] -0.85 to 0.17; lower SMD means greater improvement in depression due to omega-3 PUFA; 5 trials, 185 participants; very low-certainty evidence). Omega-3 PUFA supplementation may have little to no effect on remission of depression symptoms compared to placebo, but the evidence is very uncertain (omega-3 PUFA versus placebo: 50% versus 48%; odds ratio [OR] 1.11, 95% CI 0.45 to 2.75; 4 trials, 127 participants; very low-certainty evidence). Omega-3 PUFA supplementation may result in little to no difference in attrition (dropouts) compared to placebo (omega-3 PUFA versus placebo: 18% versus 19%; OR 0.94, 95% CI 0.46 to 1.90; 5 trials, 228 participants; low-certainty evidence). Omega-3 PUFA supplementation may result in little to no difference in adverse effects, with one study reporting more muscle cramps in the fish oil group (13/27 participants) compared to the placebo group (6/29 participants); one study reported more frequent defecation in the omega-3 group (1/29 participants) and one study identified mild skin rash and unusual/manic behavior in the placebo group (2/27 participants). None of the included studies reported serious adverse effects.

Authors' conclusions: Based on five small studies, omega-3 PUFA supplementation may reduce self-reported depression symptoms, but the evidence is very uncertain. Omega-3 PUFA supplementation may have little to no effect on depression remission compared to placebo, but the evidence is very uncertain. Omega-3 PUFA supplementation may result in little to no difference in attrition or adverse effects. The studies observed no serious adverse effects. This review highlights early-stage research on omega-3 PUFA and depression in young people. The evidence on the effects of omega-3 PUFA supplementation in improving self-reported depression symptoms or achieving depression remission in children and adolescents is very uncertain. While no harms are evident, more data are needed to confirm potential risks. Addressing current limitations in the evidence base through the design and conduct of methodologically rigorous studies - larger sample sizes, varied dosages, eicosapentaenoic acid/docosahexaenoic acid ratios, treatment durations, and safety profiles - is crucial to advance our understanding of the role of omega-3 PUFA supplementation for depression in children and adolescents.

PubMed Disclaimer

Conflict of interest statement

SCC: none.

CZ: none.

GB‐R: none.

AS: none.

PS: none.

DJK: Canadian Academy of Child and Adolescent Psychiatry (Chair, Research and Scientific Program Committee); Canadian Pediatric Society (Chair, Mental Health Task Force); Canadian Institutes of Health Research (CIHR) (Grant/Contract); Hospital for Sick Children (Grant/Contract); University of Toronto (Grant/Contract); Psychiatrist, Hospital for Sick Children.

Figures

1
1
PRISMA flow diagram
1.1
1.1. Analysis
Comparison 1: Primary outcomes, Outcome 1: Self‐reported depression symptoms (continuous measure)
1.2
1.2. Analysis
Comparison 1: Primary outcomes, Outcome 2: Depression remission (dichotomous measure)
2.1
2.1. Analysis
Comparison 2: Secondary outcomes, Outcome 1: Attrition (dropouts)
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to studies excluded from this review

Cadenhead 2017 {published data only}
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Chan 2015 {published data only}
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Kiecolt‐Glaser 2011 {published data only}
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Kooshki 2014 {published data only}
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Lesperance 2005 {published data only}
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Marangell 2003 {published data only}
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McGorry 2017 {published data only}
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NCT00511810 {published data only}
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NCT01104194 {published data only}
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NCT01341925 {published data only}
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NCT03732378 {published data only}
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Nelson 2018 {published data only}
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Rapaport 2013 {published data only}
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Rapaport 2016 {published data only}
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Robinson 2019 {published data only}
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Rodriguez‐Hernandez 2020 {published data only}
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Wozniak 2015 {published data only}
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Yang 2022 {published data only}
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References to ongoing studies

Cao 2021 {unpublished data only}
    1. ChiCTR2100041918. Study on the effect of omega-3 polyunsaturated fatty acids in adolescents with depression. trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2100041918 (first received 10 January 2021).
Haberling 2019 {unpublished data only}
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    1. NCT03167307. The Omega-3 Fatty Acid Paediatric Depression Trial (Omega-3-pMDD). clinicaltrials.gov/study/NCT03167307 (first received 24 February 2017).
Li 2022 {unpublished data only}
    1. ISRCTN68038781. Effects of ω-3 polyunsaturated fatty acid supplementation on depressive symptoms, cognition conditions and plasma metabolome in adolescent patients with depressive disorder [Effects of ω-3 polyunsaturated fatty acid supplementation in the treatment of adolescents with depressive disorder]. trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN68038781 (first received 12 March 2022). [TRIALID: https://trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN68038781]
Rice 2016 {unpublished data only}
    1. ACTRN12613001352796. Youth Depression Alleviation: a randomised controlled trial of omega-3 fatty acids (fish oil) for major depressive disorder in young people (YoDA-F). trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12613001352796 (first received 11 December 2013).
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References to other published versions of this review

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