Dual-Site aiTBS for Suicidal Ideation in Adolescents With Major Depressive Disorder

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.