Imaging- vs. scalp-targeted accelerated TMS for depression: The number needed to scan (NNS) trial

About This Grant

Project Summary A form of accelerated transcranial magnetic stimulation (aTMS) with patented imaging-based targeting called Stanford Accelerated Intelligent Neuromodulation Therapy (AINT) has shown rapid and substantial antidepressant benefits that rival or exceedthose of electroconvulsive therapy. However, the public health impact of aTMS may be limited by the time, cost, and complexity of using imaging-based targeting. Access to an MRI scanner with an optimized functional connectivity sequence may be limited by geography or insurance. Even with MRI data, most clinicians lack the expertise to derive targets and the neuronavigation equipment to stimulate them. Increasingly, consultants and companies are offering to remotely derive imaging-based targets for fees despite the paucity of prospective trials verifying that they yield significant clinical benefits over conventional scalp-based targets. In July 2023, we launched a pilot trial (NCT05680727) to estimate the effect size of imaging- based targeting for aTMS. This trial leveraged our publicly available, evidence-based, and reproducible imaging- based targeting algorithm. A blinded interim analysis (n=21) revealed 69.8% (34% SD) vs. 52.9% (27% SD) Montgomery–Åsberg Depression Rating Scale (MADRS) improvement one month after aTMS (Cohen’s d=0.52). Based on these results, a sample size of 60 per group provides 99% power to detect a between-group difference. Here, we propose a fully powered, double-blind, confirmatory efficacy trial (n=120) for imaging- vs. scalp-targeted aTMS for MDD. Aim 1 compares clinical outcomes between imaging- vs. scalp-targeted aTMS for TRD. First, we hypothesize that the imaging-targeted group will show a significantly greater MADRS reduction (%) than the scalp-targeted group. Second, we hypothesize that a larger response (≥ 50% MADRS improvement) in the imaging- vs. scalp-targeted group will reveal the “number needed to scan” for a single person to benefit from imaging-based targeting. Aim 2 investigates the relationship between target location and response in scalp-targeted aTMS for TRD. We hypothesize that clinical improvement will negatively correlate with distance between the actual scalp-based target and the predicted imaging-based target. SAINT could impact psychiatric care in many ways if it proves to be reproducible and scalable. However, we cannot address these issues until we begin to dissect SAINT into its component parts and grow aTMS in a brand-agnostic manner. The results of this study will estimate the “number needed to scan” to get a single person better with imaging- vs. scalp-targeted aTMS. Future studies could examine effectiveness, build freely available apps for imaging-based targeting (similar to Beam F3 app for scalp-based targeting), analyze cost effectiveness, or randomize people who do not respond to scalp-targeted aTMS to imaging-targeted aTMS vs. another intervention like esketamine or ECT (i.e., an interventional psychiatry equivalent of STAR*D). This trial is a step toward a future with a wider variety of scalable, publicly available, non-proprietary aTMS treatment options.