Efficacy and Safety of Polyunsaturated Fatty Acids Supplementation in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents: A Systematic Review and Meta-Analysis of Clinical Trials

Systematic review and meta-analysis of 24 clinical trials in children and adolescents aged 6 to 18 years with ADHD diagnosed by ICD-10 or DSM criteria. The pooled active-intervention sample comprised 1755 participants across the PUFA arms.

Polyunsaturated fatty acid supplementation, including omega-3 and/or omega-6 formulations, was evaluated in children and adolescents with ADHD. Treatment duration ranged from 8 weeks to 12 months; dose, frequency, and route were not consistently reported, and comparators were placebo or usual control in the included clinical trials.

PUFA supplementation did not provide a clinically meaningful benefit for ADHD symptoms or related outcomes overall. Parent-rated core symptoms showed a small improvement (SMD -0.17, 95% CI -0.32 to -0.02; k = 23), but teacher-rated symptoms were not improved (SMD -0.06, 95% CI -0.31 to 0.19; k = 10). Behavioral difficulties were null for both parent ratings (SMD -0.02, 95% CI -0.17 to 0.14; k = 7) and teacher ratings (SMD -0.04, 95% CI -0.35 to 0.26; k = 5), and quality of life was unchanged (SMD 0.01, 95% CI -0.29 to 0.31). Adverse effects were not substantially increased, including diarrhea (RR 1.08, 95% CI 0.32 to 3.63) and gastrointestinal discomfort (RR 0.72, 95% CI 0.27 to 1.88).

Certainty of evidence was low to very low because of risk of bias and imprecision. Trials were relatively small and heterogeneous in PUFA formulation and treatment duration, which limits confidence in the small parent-rated effect and the overall generalizability of the findings.