Bilateral sequential accelerated theta-burst stimulation for treatment-resistant depression: an open-label randomized controlled trial.

Abstract

This study aims to evaluate the clinical effectiveness and feasibility of a novel bilateral sequential accelerated theta-burst stimulation (BS-aTBS) protocol in treatment-resistant depression (TRD) patients, compared to a standard intermittent TBS (a-iTBS) protocol. In this randomized controlled clinical trial, 94 TRD patients were randomly assigned to receive either BS-aTBS (n = 46) or a-iTBS (n = 48). Both groups delivered 10 daily TBS sessions (1800 pulses/session) for 5 consecutive days. The primary outcome was score on the 24-item Hamilton Depression Rating Scale (HDRS-24) after treatment, normalized to baseline (week 0). Both BS-aTBS and a-iTBS protocols significantly reduced HDRS-24 scores by week 1 (65.52% vs. 54.32%, p = 0.008) and week 5 (77.10% vs. 67.77%, p = 0.006), and the BS-aTBS group showed significantly greater symptom improvement at both time points. Compared to a-iTBS, the BS-aTBS yielded higher response rates at week 1 (78.26% vs. 58.33%, p = 0.038) and week 5 (93.48% vs. 77.08%, p = 0.026), and elicited greater alleviation for anxiety and suicidal ideation at week 5. Moreover, clinical improvement on sleep quality and cognitive abilities was larger in the BS-aTBS group, and the effects on anhedonia and alexithymia were comparable between the two protocols. No serious adverse events were observed. The BS-aTBS protocol provided rapid and well-tolerated antidepressant effects in TRD patients lasting for 1 month, with additional benefits for anxiety and suicidal ideation. Considering its clinical advantages and shortened treatment time, the BS-aTBS may serve as a promising treatment protocol for TRD patients with high feasibility and efficiency. This trial was registered at Chinese Clinical Trial Registry (ChiCTR2400091459).