Real-World Evidence of SAINT® Effectiveness in a Heterogenous Clinical Population with Psychiatric and Medical Comorbidities: A Multicenter, Open-Label, Community-Based Study

ABSTRACT Objective SAINT®, a functional connectivity-guided, accelerated form of intermittent theta-burst stimulation, has shown high efficacy in depression in open-label and randomized controlled trials. To evaluate real-world effectiveness across diverse clinical practice settings, an open-label, multicenter study was conducted. Methods Adult patients with major depressive disorder who failed to achieve satisfactory improvement from prior antidepressant medication in the current episode were enrolled across 7 private psychiatric clinics in the U.S. All participants received a 5-day course of SAINT. The primary outcome was the Clinical Global Impressions Scale of Improvement (CGI-I) score following the final treatment session with CGI-S (measure of severity) collected as a secondary measure. Results A per protocol analysis of the acute outcomes data included 101 participants. All patients who initiated SAINT treatment completed the full 5-day protocol, with no treatment discontinuations due to adverse events or tolerability concerns. At the primary endpoint, treatment day 5, 68.3% of participants achieved CGI-I ≤2 ("much improved") with a mean CGI-I of 2.32. Meaningful clinical benefit (≥1 point reduction in CGI-S from baseline through 5 days following treatment) was observed in 89.1% of participants. Improvement rates did not significantly differ by baseline severity or across the clinical sites. Conclusions This analysis of the primary outcome includes the largest cohort of patients treated with SAINT to date. The results support previously reported rapid and significant improvements in depressive symptoms and extend these findings to a more clinically representative population.