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ω-3 Fatty Acids in Pediatric Major Depressive Disorder: A Randomized Clinical Trial
Multicenter double-blind RCT (n=257 Swiss youths with moderate-to-severe MDD) of adjunctive EPA-rich omega-3 (1.5 g/day; 1 g EPA + 0.5 g DHA) versus MCT placebo on top of standardized psychotherapy found no significant between-group difference in Children's Depression Rating Scale–Revised trajectory over 36 weeks (adjusted mean difference 0.77 points; P=0.49) despite biochemical adherence.
Design
- Sites: 5 Swiss child & adolescent psychiatry centers (Apr 2017–Mar 2022 enrolment)
- Population: 257 youths with moderate-to-severe MDD (ITT analysis)
- Arms: ω-3 1.5 g/day (1 g EPA + 0.5 g DHA) vs MCT placebo, both with standardised psychotherapy; antidepressants permitted per national guidance
- Primary: CDRS-R trajectory (joint mixed-effects + time-to-event model handling dropout / off-trial AD starts)
Null depression trajectory (abstract)
- CDRS-R means: similar at 12 w (45.93 vs 46.08) and 36 w (36.50 vs 36.83)
- Adjusted mean difference (active − placebo): 0.77 (95% CI −1.39 to 2.93; P = 0.49)
- Response at 12 w: 31.2% (34/109) vs 39.1% (43/110) — NS
- Remission at 36 w: 31.9% (30/94) vs 41.1% (37/90) — NS
Adherence biomarker
- Omega-3 index rose ~4.3–4.9% on active drug—confirms exposure despite null efficacy signal
Evidence hygiene
Paediatric MDD adjunct context differs from adult meta-analytic pools on marine-omega-3-supplementation—do not generalise Liao 2019-style depression SMDs to adolescents without reading indication-specific trials.
Publication
Berger G, Walitza S, Dahmen B, et al. JAMA Netw Open. 2026 Jan 2;9(1):e2452677. PMID 41481294.
Outcomes
- Primary CDRS-R trajectory (omega-3 vs placebo): adjusted mean difference 0.77 points (95% CI −1.39 to 2.93; P = 0.49) over 36 weeks—no adjunctive efficacy despite psychotherapy background.
- 12-week response 31.2% (34/109) vs 39.1% (43/110); 36-week remission 31.9% (30/94) vs 41.1% (37/90)—non-significant; omega-3 index +4.3–4.9% on active arm confirms adherence.