The Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), a refined, rapidly acting protocol of repetitive transcranial magnetic stimulation (rTMS) previously approved for treatment-resistant major depressive disorder, has demonstrated promise for reducing depressive symptoms in bipolar I disorder. A recent open-label, feasibility and safety trial indicated rapid reduction of depressive symptoms, with 60% of participants meeting remission criteria within one month post-treatment.
Key Findings
The study, led by Kevin Li, MD, from Johns Hopkins University School of Medicine, found that SAINT rapidly reduced depressive symptoms without adverse cognitive or manic side effects. The trial involved 10 participants with bipolar I disorder experiencing moderate to severe depression despite antidepressant treatment. Participants underwent 10 sessions of targeted intermittent theta burst stimulation (iTBS) daily, with 50-minute intervals, for up to 5 days.
Researchers applied structural and resting-state functional magnetic resonance imaging (fMRI) to identify the target above the scalp to focus iTBS above the dorsolateral prefrontal cortex (DLPFC). The primary outcome was the change in MADRS score from baseline. Secondary outcomes included clinical response rates (≥50% reduction in MADRS score) and remission rates (MADRS score ≤10).
Clinical Outcomes
The results indicated a mean reduction of 16.9 in MADRS scores, with a 50% response rate and a 40% remission rate immediately after treatment. Sixty percent of participants met remission criteria within the 1-month follow-up period. No serious adverse events, manic episodes, or cognitive adverse effects were reported.
Brandon Bentzley, MD, PhD, cofounder and chief scientific officer of the SAINT protocol licensee, emphasized the importance of investigating the application for patients with bipolar disorder, noting that these patients spend more time in depressive episodes than manic episodes and often do not benefit from current treatments.
SAINT iTBS: A Refined Approach
SAINT iTBS refines rTMS by delivering the same amount of brain stimulation as the weeks-long FDA-approved rTMS regimen within 5 days. Each session lasts 3 minutes, with ten sessions administered daily, separated by 50-minute intervals. This schedule is designed to amplify the antidepressant effect.
The use of fMRI to pinpoint the target for stimulation adds to the procedure's cost but increases its accuracy and effectiveness, which is crucial for patients with refractory major depression, according to Nolan Williams, MD, a coauthor of the study.
Future Directions
Li and colleagues suggest that further investigation is warranted, including double-blinded, sham-controlled trials with larger sample sizes and longer follow-up. Bentzley confirmed the intention to further investigate the SAINT protocol for bipolar depression, with plans for a larger clinical trial.
