rTMS combined with sertraline improves depressive symptoms and cognitive scores in adolescentsrTMS Combined With Sertraline May Improve Adolescent Depression

BackgroundAdolescent depression is a global health challenge. While selective serotonin reuptake inhibitors (SSRIs) like sertraline are primary treatments, their efficacy is often limited. This meta-analysis evaluates the efficacy, neurocognitive impact, and safety of adjunctive repetitive transcranial magnetic stimulation (rTMS) combined with sertraline in adolescents.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, databases including PubMed (which also covers MEDLINE), Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, and Weipu, were searched up to June 2025. Randomized controlled trials (RCTs) comparing rTMS plus sertraline versus sertraline monotherapy in adolescents were included. The primary outcomes were depressive symptom reduction (measured by HAMD-17 and HAMD-24) and clinical response rates. Secondary outcomes included cognitive function (Montreal Cognitive Assessment, MoCA) and adverse event.ResultsTwenty-four RCTs (N = 2,155), all conducted in China and published in Chinese, were included. Combination therapy significantly reduced depressive symptoms (HAMD-17: SMD = −1.06; HAMD-24: SMD = −1.39) and improved response rates risk ratio (RR = 1.18). The pooled analysis of three studies suggested that adjunctive rTMS may improve MoCA scores (SMD = 0.99); however, the certainty of evidence was low. The combination group had a slightly higher incidence of mild adverse events (RR = 1.21). Significant heterogeneity (I2>80%) and publication bias were noted; the GRADE certainty of evidence ranged from very low to moderate. Meta-regression showed treatment duration did not moderate symptom reduction. Sensitivity analysis identified extreme protocols as the primary source of heterogeneity; excluding them yielded a pooled effect of SMD = −0.74 (I2 = 17%).ConclusionAdjunctive rTMS may enhance clinical response and may improve cognitive function in sertraline-treated adolescents, with an acceptable safety profile. The cognitive finding was based on only three studies and low-certainty evidence. Given the very-low-to-moderate GRADE certainty, high heterogeneity, and geographic restriction, the effects may be overestimated. Standardized parameters appear crucial. Future multinational, sham-controlled trials utilizing updated risk-of-bias frameworks are warranted to confirm these findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251118447.