Published in JAMA Network Open, the study by Gregor Berger of the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital, University of Zürich, and colleagues evaluated whether ω-3 fatty acid supplementation could improve outcomes in pediatric major depressive disorder (MDD). Although ω-3 fatty acids have been widely promoted for depression, evidence in children and adolescents remains limited and inconsistent, raising concerns that reliance on unproven supplements may delay evidence-based treatment.
The multicenter, double-blind, placebo-controlled randomized clinical trial was conducted across five child and adolescent psychiatry centers in Switzerland. A total of 257 youths with moderate-to-severe MDD were enrolled between 2017 and 2022 and followed for 36 weeks. Participants were randomly assigned to receive either ω-3 fatty acids or a placebo alongside standardized psychotherapy. Antidepressant medications were permitted when clinically indicated, in accordance with national guidelines.
Those in the intervention group received 1.5 g per day of ω-3 fatty acids, comprising 1 g of eicosapentaenoic acid and 0.5 g of docosahexaenoic acid in a 2:1 ratio, while the control group received a medium-chain triglyceride placebo. The primary outcome was change in depression severity measured using the Children’s Depression Rating Scale–Revised (CDRS-R). Secondary outcomes included treatment response, remission, quality of life, suicidality, antidepressant use, and safety.
The study led to the following notable findings:
- Participants had a mean age of 15.7 years, with females accounting for 73% of the study population.
- Depression severity decreased over time in both the ω-3 and placebo groups, with no significant differences observed between the two arms.
- Mean Children’s Depression Rating Scale–Revised scores were comparable between groups at 12 weeks and remained similar at 36 weeks.
- The adjusted difference in depression scores between the ω-3 and placebo groups was small and not statistically significant.
- Clinical response at 12 weeks was observed in about one-third of participants receiving ω-3 supplements and in just under 40% of those receiving placebo.
- Remission rates at 36 weeks were modest and did not differ meaningfully between the two groups.
- Self-rated depression, quality of life, and suicidality improved over time in both groups without any advantage of ω-3 supplementation.
- Treatment adherence was high, as reflected by significant increases in blood ω-3 levels among participants in the supplementation arm.
- Serious adverse events, including suicide attempts, occurred in both groups, with none considered related to the study medication.
"Overall, the findings do not support the use of 1.5 g of ω-3 fatty acids as an adjunct to psychotherapy for pediatric MDD. The authors noted that future studies should explore EPA-enriched formulations and biomarker-guided strategies to identify more effective treatments for depression in young patients," the authors concluded.
Reference:
Berger G, Häberling I, Emery S, et al. ω-3 Fatty Acids in Pediatric Major Depressive Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(1):e2548703. doi:10.1001/jamanetworkopen.2025.48703
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