Dual-Site aiTBS Reduces Suicidal Ideation in Adolescents With MDD

Key Takeaways

• Dual-site aiTBS was associated with a greater short-term reduction in suicidal ideation than single-site left DLPFC stimulation over 4 days.
• Daily suicidal ideation trajectories and day-4 depression response and remission rates also favored dual-site treatment.
• No serious adverse events were reported, and most between-group differences at 1 month were not significant except for BHS.

In adolescents with major depressive disorder and suicidal ideation, dual-site aiTBS was linked to a larger day-4 reduction in Beck Scale for Suicide Ideation scores than single-site treatment in a randomized clinical trial in JAMA Network Open, with a between-group difference of 4.94 points. The comparison paired active stimulation of the left DLPFC and left cerebellum with active left DLPFC stimulation plus sham cerebellar stimulation over 4 days. Participants were adolescents with major depressive disorder and current suicidal ideation who received a compressed four-day treatment course to test whether cerebellar stimulation added benefit.

The double-blind, randomized, sham-controlled, single-center trial was conducted at the First Affiliated Hospital of Jinan University in Guangzhou, China, from September 2023 to May 2025. Among 79 adolescents screened, 59 participants aged 12 to 18 years enrolled, the mean age was 14.78 years, and baseline characteristics were similar between groups. Randomization assigned 29 participants to dual-site aiTBS and 30 to single-site aiTBS, with participants, assessors, and clinical staff blinded throughout treatment. Dual-site treatment delivered active left DLPFC and left cerebellar stimulation, while the comparator paired active left DLPFC treatment with sham cerebellar stimulation in 600-pulse sessions. Participants received five sessions daily for four days at 80% of resting motor threshold, totaling 12,000 pulses, and the primary endpoint was BSI change from baseline to day 4.

By day 4, mean BSI scores fell by 14.34 points with dual-site treatment and by 9.40 points with single-site treatment. The between-group estimate had a 95% CI of 0.73 to 9.14, with P = 0.02 and Cohen d = 0.61. Daily BSI differences favored the dual-site group across all four treatment days.

Secondary outcomes included C-SSRS, BDI, MADRS, HAMA, and BHS scores, and daily C-SSRS trajectories also favored dual-site treatment during the intervention. Day-4 depression response and remission rates were higher with dual-site treatment, at 72% versus 43% and 45% versus 20%. Suicidal ideation response and remission rates were numerically higher with dual-site treatment but were not significantly different between groups. At the 1-month follow-up, between-group differences were not significant for BSI or BDI, while BHS continued to favor dual-site treatment on self-report assessment. No serious adverse events were reported; pain at stimulation sites occurred in 14 of 456 exposures, and dizziness occurred in 10 of 228 sessions. All events resolved within about 30 minutes after treatment.