Omega-3 Supplements Show No Benefit for Pediatric Major Depression in RCT
Key Clinical Summary
- In a multicenter randomized clinical trial, adjunctive omega-3 fatty acid supplementation did not improve depressive symptoms in children and adolescents with moderate-to-severe major depression eceiving standardized psychotherapy.
- Rates of treatment response, remission, suicidality, and quality-of-life improvement were similar between omega-3 and placebo groups over 36 weeks.
- Findings highlight the importance of prioritizing evidence-based interventions over unproven adjunctive therapies in pediatric depression care.
A multicenter randomized clinical trial conducted in Switzerland found that adding omega-3 fatty acid supplements to standardized psychotherapy did not improve outcomes in children and adolescents with moderate-to-severe major depression. Results from the study were published in JAMA Network Open.
Omega-3 supplements are commonly used off-label in pediatric psychiatry despite limited randomized evidence.
“Despite widespread belief in the mood-enhancing properties of omega-3 fatty acids, supported by multiple meta-analyses and expert panels, our findings emphasize the need for rigorous evaluation of even seemingly benign interventions,” wrote Gregor Berger, MD, Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland, and co-authors. “Promoting ineffective treatments risks delaying effective care and may worsen outcomes for adolescents with depression.”
Study Design and Population
To evaluate the efficacy of omega-3 fatty acid supplementation, the authors enrolled 257 youths with major depressive disorder (MDD) from 5 Swiss child and adolescent psychiatry centers between April 2017 and March 2022. The participants were randomized to receive omega-3 fatty acids (1.5 g/d; 1 g eicosapentaenoic acid [EPA] and 0.5 g docosahexaenoic acid [DHA], 2:1 ratio) or medium-chain triglyceride placebo, in combination with standardized psychotherapy. Participants were permitted to use antidepressants and were followed up with for 36 weeks.
The primary outcome was the trajectory of Children’s Depression Rating Scale-Revised (CDRS-R) scores analyzed with a joint mixed-effects and time-to-event model. Dropout or initiation of off-trial antidepressant therapy were accounted for. Secondary outcomes included treatment response (≥30% reduction in CDRS-R scores), remission (CDRS-R score ≤28), self-rated depression, quality of life, suicidality, and safety.
Key Findings
Of the participants (mean [SD] age, 15.7 [1.7] years; 188 [73.2%] female; mean [SD] CDRS-R score, 58.5 [8.8]), 129 received omega-3 supplements and 128 received placebo. Researchers observed a similar decrease in mean CDRS-R scores in both groups, with an adjusted mean difference in scores of 0.77 (95% CI, -1.39 to 2.93; P = .49) points. Response occurred in 31.2% of omega-3 recipients vs 39.1% of placebo recipients at week 12. Remission at week 36 occurred in 31.9% of omega-3 recipients vs 41.1% placebo recipients, with no significant difference observed. Secondary measures and suicidality improved without significant differences between groups.
Limitations and Future Directions
The authors noted that findings may be limited by the multicenter, clinical design, and were likely influenced by the COVID-19 pandemic. They also did not control for media use, a key moderator of depression in adolescents.
While conducted in Swiss psychiatry centers, the study’s design and outcomes may be relevant to other high-income countries with similar standards of pediatric mental health care. The findings underscore the importance of prioritizing evidence-based interventions when treating pediatric major depressive disorder.
“Future studies may need to focus on more specific subgroups, such as those with recurrent depression or inflammation-linked depression, while also considering the influence of modern psychosocial stressors like social media use,” Berger et al. concluded.
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