Dual-Site aiTBS for Suicidal Ideation in Adolescents With Major Depressive Disorder: A Randomized Clinical Trial

AI Summary

Dual-site aiTBS targeting the left DLPFC and cerebellum produced significantly greater reduction in suicidal ideation at day 4 versus single-site aiTBS (difference 4.94 points).
Trial demonstrated a moderate effect size (Cohen d 0.61) and statistical significance (P = .02), indicating clinical efficacy in adolescents with MDD.
Intervention was well tolerated with no serious adverse events, supporting feasibility and safety for rapid antisuicidal treatment in adolescents.

JAMA Netw Open. 2026 May 1;9(5):e2613178. doi: 10.1001/jamanetworkopen.2026.13178.

ABSTRACT

IMPORTANCE: Accelerated intermittent theta burst stimulation (aiTBS) is an effective rapid-acting treatment for suicidal ideation in adults with major depressive disorder (MDD). However, evidence in adolescents remains limited, and whether dual-site frontal-cerebellar aiTBS enhances antisuicidal efficacy in this population is unknown.

OBJECTIVE: To investigate the clinical effectiveness and safety of dual-site aiTBS targeting the left dorsolateral prefrontal cortex (DLPFC) and cerebellum vs single-site DLPFC aiTBS for reducing suicidal ideation in adolescents with MDD.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, randomized clinical trial with a 1-month follow-up was conducted at the First Affiliated Hospital of Jinan University (Guangzhou, China) from September 2023 to May 2025. Adolescents (aged 12-18 years) with MDD and suicidal ideation and without comorbid medical or neurologic conditions were enrolled and randomly assigned to dual-site aiTBS or single-site aiTBS.

INTERVENTIONS: Patients received 5 daily sessions of aiTBS over 4 days. Dual-site aiTBS delivered active stimulation to both the left DLPFC and left cerebellum, while single-site aiTBS delivered active stimulation to the left DLPFC with sham stimulation to the left cerebellum.

MAIN OUTCOME AND MEASURE: The primary outcome was the change from baseline to day 4 in the Beck Scale for Suicide Ideation (BSI) score (range, 0-38; higher scores indicate greater severity of suicidal ideation), assessed with a linear mixed-effects model.

RESULTS: Of 79 adolescents assessed for eligibility, a total of 59 were included (45 females [76%]; mean [SD] age, 14.78 [1.72] years). Of these, 29 were randomized to the dual-site aiTBS group (23 [79%] female) and 30 to the single-site group (22 [73%] female). For the primary outcome, patients receiving dual-site aiTBS showed a significantly greater reduction in mean BSI scores compared with those receiving single-site aiTBS at day 4 (difference, 4.94 points [95% CI, 0.73-9.14 points]; t = 2.35; P = .02; Cohen d, 0.61 [95% CI, 0.09-1.13]). No serious adverse events in either group were observed.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that dual-site aiTBS targeting the left DLPFC and cerebellum was more effective than single-site left DLPFC aiTBS in reducing suicidal ideation for adolescents with MDD and was well tolerated. The findings suggest this protocol may be a promising strategy for rapid reduction of suicidal ideation in the adolescent population.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2300068954.

PMID:42154469 | DOI:10.1001/jamanetworkopen.2026.13178

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