Ketamine for major depression in adolescents: a systematic review and meta-analysis of efficacy and safety

Major depressive disorder (MDD) significantly impairs adolescents' development, with increasing rates of treatment resistance and suicide risk. Ketamine has emerged as a promising, rapid-acting antidepressant in adults, but its efficacy and safety in adolescents remain unclear. This systematic review and meta-analysis aimed to evaluate short-term outcomes of ketamine administration in youth with mood disorders. Following PRISMA guidelines and PROSPERO registration (CRD42024568658), four studies were included, comprising 272 adolescents aged 12-18 years. Three studies (n = 189) contributed data to the meta-analysis. At 24 hours post-administration, ketamine showed a small, non-significant effect on depressive symptoms compared to placebo (SMD = -0.19; 95% CI: -0.41 to 0.04). Clinical response and remission were not significantly different between groups, but ketamine was associated with a significantly higher rate of suicidal ideation remission (RR = 1.49; 95% CI: 1.06 to 2.08). Adverse events were generally mild, transient, and consistent with known pharmacological effects. While findings support ketamine's potential role in acute presentations, current evidence is preliminary. Larger randomized controlled trials with extended follow-up are needed to clarify the clinical utility, optimal protocols, and long-term safety of this approach in adolescent populations.