Clinical efficacy of intermittent theta burst stimulation in the acute phase of adolescent depression: study protocol of a double-blind, randomized controlled trial

BACKGROUND: Adolescent depression is a significant health problem, and developing safe and rapid treatments for it is crucial. Intermittent theta burst stimulation (iTBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), enhances synaptic transmission and cortical excitability by simulating cortical rhythms and has demonstrated certain therapeutic effects in adults. Adolescents in the acute phase of depression present with more severe symptoms and are pressed for time, so a short, effective modality like iTBS could be particularly advantageous. However, studies on the effects of iTBS during the acute phase of adolescent depression are still fairly limited. Therefore, this study aims to explore the clinical efficacy of iTBS in adolescents with depression during the acute phase through a viable research design. METHODS: This is a single-center, randomized, double-blind, and sham-stimulation-controlled clinical trial. We plan to recruit approximately 76 adolescent patients with depression aged 14-18 years. Eligible participants will be randomly assigned to the treatment group (n = 38) or the sham control group (n = 38). Each participant will receive 10 sessions of iTBS over 10 days, delivered at 80% of the active threshold, with 1,800 pulses per session. The treatment target will be the left dorsolateral prefrontal cortex. Clinical and neurophysiological assessments will be conducted at baseline, at the end of treatment, and during follow-up at weeks 2 and 4 after treatment completion. Safety will be monitored through semi-structured interviews and the reporting of adverse events. DISCUSSION: Conventional rTMS treatment faces logistical challenges due to its standard course requiring daily treatment over 4-6 weeks. This study aims to explore a safe and effective iTBS protocol for adolescent patients with depression to complement existing treatments. By evaluating clinical symptoms and the most sensitive neurophysiological features after treatment, we hope to optimize the iTBS protocol. This study aims to reduce the treatment duration, alleviate the economic burden on families and society, and expedite the clinical response for adolescent patients. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry. REGISTRATION NUMBER: ChiCTR2500101152. Retrospectively registered on 21 April 2025.