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Objective: To quantify dose-response associations of total pulse dose and intersession interval with antidepressant outcomes in accelerated repetitive transcranial magnetic stimulation (rTMS), with more than one treatment session per day, for major depressive episodes. Methods:A systematic review and dose-response meta-analysis of total pulses and intersession interval was conducted, stratified by sham-controlled randomized controlled trials (RCTs) versus non-sham-controlled trials/observational studies, using linear, quadratic, and restricted cubic spline models.Fifty-nine studies (2,908 participants) were included.Outcomes were symptom change (standardized mean difference; Hedges' g), response, and remission.Results: Among the included accelerated rTMS protocols, total pulses ranged from 10,800 to 120,000 (median 36,000), and intersession intervals ranged from 10 to 480 minutes (median 50).Across sham-controlled RCTs, higher total pulses showed a consistent positive association with efficacy, response, and remission.In non-sham-controlled trials and observational studies, the association was clearer for response and remission than for continuous symptom improvement.In sham-controlled RCTs, intersession interval showed a non-linear (bell-shaped) association, with intermediate spacing (roughly 30-75 minutes) generally outperforming shorter or longer intervals; findings in non-sham-controlled evidence were mixed.Compared with session number or pulses per session, total pulses appeared to be a more informative dose metric. Conclusions:Total pulse count generally appears to follow a "more is better" pattern, and intersession interval may show a non-linear association with outcomes.This meta-analysis offers J o u r n a l P r e -p r o o f a quantitative framework that may help inform parameter optimization and guide future trials aimed at refining and standardizing accelerated protocols for clinical implementation.
Wang et al. (Fri,) studied this question.