Rapid and robust effects of high-dose intermittent Transcranial Brain Stimulation (iTBS) on depression and suicidal ideation in adolescents with acute major depression: a 10-day randomised, controlled, single-blind trial

BACKGROUND: Depression is extremely common among adolescents and can significantly increase the risk of suicide when severe. High-dose intermittent theta burst stimulation (iTBS) is a secure and efficacious physical treatment. However, clinical evidence in adolescents remains limited. This research is designed to assess the therapeutic impacts of high-dose iTBS on depressive symptoms, anxiety symptoms, and suicidal ideation in adolescents suffering from acute depression, along with the factors linked to treatment response. METHODS: A total of 61 patients were randomly assigned to either the high-dose iTBS group or the sham stimulation group. All participants received 10 daily sessions of high dose iTBS stimulation over a two-week period, targeting the left dorsolateral prefrontal cortex (DLPFC). Outcome measures assessed at baseline, post-intervention, and 1-month follow-up included 24-item Hamilton Depression Rating Scale (HAMD-24) scores, Beck Scale for Suicide Ideation - Chinese Version (BSI-CV), and Hamilton Anxiety Rating Scale (HAMA). Clinical factors influencing iTBS efficacy were further analyzed. RESULT: At the end of the 10-day intervention, the high-dose iTBS group exhibited significantly lower HAMD-24 (p = 0.008, Cohen`s d = 0.71 [95%CI: 0.188-1.224]) and BSI-CV (p = 0.011, Cohen`s d = 0.67[95%CI: 0.154-1.186]) scores compared with the sham group, and this advantage persisted at the 1-month follow-up (Week 6) (HAMD-24: Cohen`s d = 0.96[ 95%CI: 0.43-1.49]; BSI-CV: Cohen`s d = 0.76[95%CI: 0.24-1.28]). In contrast, between-group differences in HAMA scores were non-significant both post-intervention (Week 2) and at the 1-month follow-up (Week 6) (p > 0.05). Moreover, poorer family functioning within the high-dose iTBS cohort was associated with diminished therapeutic benefit (p < 0.05). CONCLUSION: Current research indicates that a 10-day course of high-dose iTBS is effective in alleviating depressive symptoms and suicidal ideation in adolescents with depression, and that the therapeutic effects persist for up to one month after the end of treatment. We also found that high-dose iTBS was less effective in patients with poor baseline family functioning. TRIAL REGISTRATION: Chinese clinical trial Registry (ChiCTR2500101152), trial registration date: April 21, 2025(retrospectively registered).