GLP-1 Receptor Agonists and Psychiatric Outcomes in Adolescents: A Systematic Review and Meta-Analysis.

AIMS: To assess the association between GLP-1 receptor agonists (GLP-1 RAs) and psychiatric outcomes in adolescents. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, EMBASE and the Cochrane Library. We included randomized controlled trials (RCTs) and observational cohort studies of adolescents that compared GLP-1 RAs prescribed for overweight, obesity or type 2 diabetes with placebo, no treatment or standard of care. We assessed suicidal ideation, suicide attempts and depression. We pooled risk ratios with 95% confidence intervals (CIs). We assessed heterogeneity with I and χ and used sensitivity and subgroup analyses to test robustness of our data. We assessed risk of bias using RoB 2 (randomized trials) and ROBINS-I (observational studies) tools. We graded the certainty of evidence using the GRADE framework. RESULTS: We included 11 studies (9 RCTs, n = 1253; 2 observational, n = 8922; total n = 10 175). GLP-1 RAs were associated with a lower risk of suicidal ideation versus control (RR 0.73; 95% CI: 0.54-0.99; p = 0.046; I  = 0%). We found no significant effects versus control on suicide attempts (RR 0.66; 95% CI: 0.16-2.61; p = 0.444; I  = 0%) or depressive symptoms (RR 0.73; 95% CI: 0.36-1.48; p = 0.282; I  = 50.4%). CONCLUSIONS: GLP-1 RAs were not associated with higher rates of suicidal behaviour or depression in adolescents. Pooled analysis suggested a possible lower risk of suicidal ideation, although this finding should be interpreted cautiously.