Pilot Randomized Trial of Intermittent Theta-Burst Stimulation versus H-Coil Transcranial Magnetic Stimulation for Treatment-Resistant Depression

ABSTRACT Background Intermittent theta burst stimulation (iTBS) and H-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. Methods Twenty-eight adults with TRD were randomized to six weeks of iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) using a figure-8 coil (n=15) or H-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) using a H7-coil (n=13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. Results Twenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference −0.40, 95% CI −5.23 to 4.43; p=.865). Response rates were 40.0% for iTBS and 50.0% for H-coil (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. Conclusion In this pilot trial, iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group pattern. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. Trial registration ClinicalTrials.gov ( NCT05902312 )