Effect of iTBS on suicidal ideation and emotion regulation in major depressive disorder: a randomized clinical trial

BACKGROUND: Major depressive disorder (MDD) with suicidal ideation (SI) is a psychiatric emergency characterized by high risk and a critical need for timely adjunctive intervention. Traditional antidepressants often exhibit a significant therapeutic lag. This study evaluated the efficacy of a 10-day intermittent theta burst stimulation (iTBS) protocol as an adjunctive neuromodulation strategy to alleviate depressive symptoms and suicidal ideation by restoring emotion regulation capacities. METHODS: In this prospectively registered, randomized, double-blind, sham-controlled clinical trial using a pre-specified 2:1 allocation ratio, 78 patients with MDD and SI were assigned to active iTBS plus stable medication management (n = 52) or matched sham stimulation plus stable medication management (n = 26) for 10 consecutive treatment days. The primary outcome was the Hamilton Depression Rating Scale (HAMD-17) score. Secondary outcomes included the Beck Scale for Suicide Ideation (BSSI), Hamilton Anxiety Rating Scale (HAMA), and Emotion Regulation Questionnaire (ERQ). RESULTS: The iTBS group demonstrated a greater reduction in HAMD-17 scores than the sham group, with a significant Group x Time interaction (F(1, 76) = 117.055, p < .001, partial eta-squared = 0.606). For suicidal ideation, the active iTBS group also showed a larger reduction in BSSI scores (post-treatment between-group comparison, p = .003). iTBS treatment significantly enhanced cognitive reappraisal (F(1, 76) = 51.214, p < .001, partial eta-squared = 0.403), and improvement in cognitive reappraisal was negatively correlated with reduction in depressive severity (r = - .455, p = .001). Improvements in anxiety and sleep quality were also greater after active iTBS, whereas digit-span performance remained comparable between groups. CONCLUSION: A 10-day protocol of active iTBS added to stable medication management was associated with greater baseline-to-post-treatment reductions in depressive symptoms and suicidal ideation, together with improvement in adaptive emotion regulation. Because assessments were performed only at baseline and after treatment, these findings should be interpreted as short-term post-treatment effects rather than evidence of a measured time-to-response trajectory. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06417437; registered before participant recruitment (registration date: 23 April 2024).