Personalized Accelerated iTBS Versus Sham for Major Depressive Disorder

Brief Summary

This randomized, double-blind, sham-controlled, parallel-group clinical trial will evaluate the efficacy and safety of individualized functional connectivity-guided accelerated intermittent theta-burst stimulation (iTBS) in adults with major depressive disorder (MDD). A total of 90 participants will be randomly assigned in a 1:1 ratio to receive either active iTBS or matched sham stimulation. Treatment will be administered over 5 consecutive days, with 10 stimulation sessions per day. For each participant, an individualized stimulation target within the left dorsolateral prefrontal cortex will be identified using resting-state functional magnetic resonance imaging (MRI). The primary objective is to compare the change in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), from pre-treatment baseline (Day -1) to 4 weeks post-treatment (Week 4; Day 34) between the active and sham groups. Changes in other clinical symptoms, treatment response, remission, and safety will also be assessed during follow-up through 8 weeks after treatment. Multimodal MRI, resting-state electroencephalography (EEG), and transcranial magnetic stimulation combined with EEG (TMS-EEG) will be collected at prespecified time points. These measures will be used to explore treatment-related changes in brain function and connectivity and to identify potential neuroimaging and neurophysiological biomarkers associated with clinical improvement and the maintenance of treatment effects.