Safety and Efficacy of Omega-3 Fatty Acids for Depressive Disorders in Children and Adolescent Depression: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis: Efficacité et innocuité des acid
Abdullah M. Alharran, Mariam M. Abdulraheem, Bader Sabeq, Mohammad Alsowailem, Khaled Alsalem, Manal Alharbi, Hasan Alhusainan, Dana K. Alkandari, Shekha Alnajdi, Ali Faisal Alasfoor, Waleed Bader Alazemi, Abdulrahman Hamad AldousariBackground
Depression in children and adolescents is a leading cause of disability worldwide, with rising prevalence and limited efficacy of conventional pharmacotherapies. Omega-3 polyunsaturated fatty acids (PUFAs) have emerged as a potential adjunctive or alternative treatment due to their anti-inflammatory and neuroprotective properties. However, evidence in paediatric populations remains inconclusive. This updated meta-analysis aims to evaluate the efficacy and safety of omega-3 PUFA supplementation versus placebo or standard care for depressive symptoms in children and adolescents.
Methods
We conducted a systematic search for randomized controlled trials (RCTs) comparing omega-3 PUFA supplementation in children and adolescents with depressive disorders or clinically significant depressive symptoms. For the meta-analysis, we used R software (version 4.5.0) with the meta and metasens packages. Using a random-effects model, we evaluated continuous outcomes using standardized mean differences (SMDs) and dichotomous outcomes using risk ratios (RRs), each with 95 per cent confidence intervals (95% CIs). Trial sequential analysis (TSA) was performed to assess the robustness of findings and calculate required information sizes (RISs).
Results
We included nine RCTs with a total of 848 participants. There were no statistically significant differences between omega-3 and control groups in change in depression symptom severity at any follow-up duration: 3–4 weeks, 6–8 weeks, 10–12 weeks, 16 weeks, or 24–26 weeks. Heterogeneity was significant across most subgroups, with I 2 ranging between 67.1 per cent and 91.8 per cent. Similarly, no significant effects were observed for response rate or remission rate at any time point, or all-cause dropouts. TSA indicated that the cumulative evidence did not reach the RIS.
Conclusion
Omega-3 did not significantly improve depressive symptoms or remission in children and adolescents. However, TSA showed that the evidence remains underpowered, so a potential benefit cannot be excluded. Significant clinical heterogeneity and insufficient information size underscore the need for large-scale RCTs with standardized outcome measures.