Accelerated TMS with the H1-coil for depression: A multisite, randomized non-inferiority trial

BACKGROUND: Transcranial magnetic stimulation with the H1-coil is an FDA-cleared treatment for major depressive disorder (MDD), traditionally delivered once daily over six weeks. Accelerated protocols condense treatment by administering multiple sessions per day. This multisite, randomized, blinded non-inferiority trial compared a five-times-daily accelerated intermittent theta burst stimulation (ACC-iTBS) protocol with the standard of care high-frequency (SOC-HF) H1 coil TMS protocol in adults with MDD. METHODS: 104 adults with moderate-to-severe MDD were randomized to: (1) ACC-iTBS (110%rMT, H1 coil): 5 sessions/day for 6 days (30 sessions) over 2 weeks, plus 2 sessions/day one day/week for 4 weeks (8 sessions); or (2) SOC-HF (120%rMT, H1 coil): once-daily sessions for 4 weeks (20 sessions), followed by 2 sessions/week for 2 weeks (4 sessions). The primary endpoint was change in HDRS-21 score at week 6. Secondary outcomes included response, remission, anxiety, and adverse events. RESULTS: 89 participants completed the 6-week study enrollment (ACC-iTBS: 41; SOC-HF: 48). Both groups showed significant HDRS-21 improvement at week 6 (ACC-iTBS: -19.02 points; SOC-HF: -19.79; p < 0.001), with a non-significant between-group difference (0.76, p = 0.78), and upper limit of the one-sided 97.5% CI was 2.73 (< inferiority margin δ = 3.0 points on the HDRS-21). ACC-iTBS showed faster symptom reduction by week 2 (median HDRS change: -11.70 vs. -8.590) and shorter time to remission (21 vs. 28 days; p = 0.0324). Week 6 response/remission rates were 87.8%/78.0% (ACC-iTBS) and 87.5%/87.5% (SOC-HF). Anxiety also improved in both groups. Adverse events, including treatment-site discomfort and headaches, were more common with ACC-iTBS. Blinding was preserved. CONCLUSIONS: ACC-iTBS TMS with the H1 coil is a safe, well-tolerated, and time-efficient alternative to standard HF H1-coil TMS, offering comparable outcomes and faster remission.