Number of pulses or number of sessions? An open-label study of trajectories of improvement for once-vs. twice-daily dorsomedial prefrontal rTMS in major depression

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) shows efficacy in the treatment of major depressive episodes (MDEs), but can require ≥4-6 weeks for maximal effect. Recent studies suggest that multiple daily sessions of rTMS can accelerate response without reducing therapeutic efficacy. However, it is unresolved whether therapeutic effects track cumulative number of pulses, or cumulative number of sessions. OBJECTIVE: This open-label study reviewed clinical outcomes over a 20-30 session course of high-frequency bilateral dorsomedial prefrontal cortex (DMPFC)-rTMS among patients receiving 6000 pulses/day delivered either in twice-daily sessions 80 min apart (at 20 Hz) or single, longer, once-daily sessions (at 10 Hz). METHODS: A retrospective chart review identified 130 MDD patients who underwent 20-30 daily sessions of bilateral DMPFC-rTMS (Once-daily, n = 65; Twice-daily, n = 65) at a single Canadian clinic. RESULTS: Mixed-effects modeling revealed significantly faster improvement (group-by-time interaction) for twice-daily versus once-daily DMPFC-rTMS. Across both groups, the pace of improvement showed a consistent relationship with number of cumulative sessions, but not with cumulative number of pulses. Although the twice-daily group completed treatment in half as many days, final clinical outcomes did not differ significantly between groups on dichotomous measures (response/remission rates: once-daily, 35.4%/33.8%; twice-daily, 41.5%/35.4%), or continuous measures, or on overall response distribution. CONCLUSIONS: Twice-daily rTMS appears feasible, tolerable, and capable of achieving comparable results to once-daily rTMS, while also reducing course length approximately twofold. Therapeutic gains tracked the cumulative number of sessions, not pulses. Future randomized studies comparing once-daily to multiple-daily rTMS sessions, while controlling for number of pulses, may be warranted.