Treatment-resistant depression (TRD) is a debilitating condition occurring in major depressive disorder (MDD) and bipolar II disorder (BP-II). Intermittent theta burst stimulation (iTBS) is an established neuromodulation approach for TRD, but standard delivery requires once-daily sessions over several weeks. Accelerated iTBS (aiTBS) may reduce treatment burden by temporally compressing delivery. We evaluated the implementation, tolerability, and clinical outcomes associated with a 5-day aiTBS schedule for adults experiencing TRD in MDD and BP-II.

In this single-center, open-label, uncontrolled, prospective naturalistic cohort study, adults with MDD or BP-II experiencing TRD received 30 iTBS sessions (600 pulses/session; total 18 000 pulses) over 5 days with 50-minute inter-session intervals. HAMD-17 was assessed at baseline, post-treatment, and 2-month follow-up. Secondary outcomes included Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), baseline Clinical Global Impression-Severity (CGI-S), post-treatment/follow-up CGI-I, response/remission rates, and adverse events. Longitudinal changes were evaluated using linear mixed-effects models.

Forty-six participants contributed longitudinal data (mean age 44.3 years; 54.4% male). HAMD-17 response rates were 28.3% (n = 13) post-treatment and 37.0% (n = 17) at follow-up; remission rates were 26.1% (n = 12) and 32.6% (n = 15), respectively. Improvements were also observed on PHQ-9 and GAD-7. On CGI-I, 52.2% were rated improved post-treatment and 60.9% at follow-up. The most common adverse event was transient, non-serious stimulation-site pain.

The 5-day aiTBS schedule was logistically feasible, well-tolerated, and associated with reductions in depressive and anxiety symptom scores in a real-world TRD cohort. Randomized sham-controlled trials are needed to confirm these findings.