Systematic review and meta-analysis on the efficacy and safety of combining repetitive transcranial magnetic stimulation with sertraline for adolescent depression in China
4 affiliations
- 1Xiamen Key Lab of Psychoradiology and Neuromodulation, Function Testing and Modulation Center for Neurological, West China Hospital, West China Xiamen Hospital, Sichuan University
- 2Department of Rehabilitation, Jintang First People’s Hospital
- 3Clinical Psychology Department, Zhongshan Third People’s Hospital
- 4Neurobiological Detection Center, West China Hospital, Sichuan University
Abstract
Background: Adolescent 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.
Methods: Following 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.
Results: Twenty-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%).
Conclusion: Adjunctive 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 registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251118447.
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BibTeX
@article{sun2026systematic,
title = {{Systematic review and meta-analysis on the efficacy and safety of combining repetitive transcranial magnetic stimulation with sertraline for adolescent depression in China}},
author = {Hongyi Sun and Lin Zhang and Jing Hu and Jing Li and Zhong Zheng},
journal = {Frontiers in Psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1893010},
url = {https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1893010/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Systematic review and meta-analysis on the efficacy and safety of combining repetitive transcranial magnetic stimulation with sertraline for adolescent depression in China
AU - Hongyi Sun
AU - Lin Zhang
AU - Jing Hu
AU - Jing Li
AU - Zhong Zheng
PY - 2026
DA - 2026/10/22
JO - Frontiers in Psychiatry
DO - 10.3389/fpsyt.2026.1893010
UR - https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1893010/full
AB - Background: Adolescent 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. Methods: Following 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. Results: Twenty-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%). Conclusion: Adjunctive 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 registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251118447.
SN - 1664-0640
ER -