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

Abstract

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.