Efficacy and safety of repetitive transcranial magnetic stimulation in youth with depression: a systematic review and meta-analysis of randomized sham-controlled trials.

BACKGROUND: Major depressive disorder is a major cause of disability and health-related burden globally. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative therapy for major depressive disorder in adults, but its efficacy and safety in 10-25 years (youth) with depression remains inconclusive. We aim to evaluate the efficacy and safety of rTMS in youth with depression in randomized sham-controlled trials. METHODS: A comprehensive search of nine databases was conducted from inception to April 30, 2025. Trials using random assignment with a sham control group were selected. Heterogeneity among studies was assessed using the I2 and Cochran Q test. A random-effects model was employed when I2 > 50%. Standard mean deviation (SMD) for depression rating scale scores and risk difference (RD) with corresponding 95% confidence intervals (CIs) of adverse event were used to evaluate efficacy and safety, respectively. RESULTS: Sixteen studies with 1295 patients aged 10-25 years were included. Meta-analysis showed that active rTMS significantly reduced depression scale scores (SMD = - 0.93, 95% CI = - 1.31 to - 0.55). Subgroup analysis revealed significant relief of depressive symptoms at the second week (SMD =  - 0.66, 95% CI = - 1.25 to - 0.07) and persisting at the fourth week (SMD =  - 1.28, 95% CI = - 1.82 to - 0.75) when compared to sham stimulation. Pooled RR was 1.24 (95% CI = 1.06-1.45) for response rate and 1.63 (95% CI = 1.11-2.39) for remission rate (with an associated number needed to treat of 10). CONCLUSIONS: Evidence indicates that rTMS is effective, safe and exhibits a relatively rapid onset of action for treating youth depression. Larger-scale studies with longer treatment durations and extended follow-up periods are essential to understand and characterize the short- and long-term neuromodulatory effects within this vulnerable population. The effect of rTMS in treatment-resistant depression and its use across diverse populations also need further investigation.