SAINT TMS for Treatment-Resistant Depression: Individualized Neuromodulation

Brandon Bentzley, MD, PhD, described the clinical rationale, mechanism, and access landscape for the SAINT transcranial magnetic stimulation (TMS) protocol in treatment-resistant depression.

Bentzley framed the central clinical problem as one of time: all existing treatments for depression require weeks to months to produce benefit, a timeline that is incompatible with the acuity of patients presenting in crisis and with the average US psychiatric hospitalization length of 7 to 9 days.¹ SAINT was developed to address this gap by achieving remission within 5 days or fewer. He reported that in clinical trials, patients entered remission at an average of 2.6 days, stating that the protocol achieves this by tailoring treatment to the individual patient's neuroanatomy: "instead of using neuromodulation that's not targeted, we actually tailor the treatment to the person's brain," he said.

The individualization process relies on structural and functional MRI prior to treatment. Bentzley used an analogy to explain the approach: "when we do a structural MRI, we see where the roads are—we do the functional MRI, we see what the traffic looks like, and by doing that we can figure out exactly how to modify that traffic in order to get the person out of depression as fast as possible." He noted that SAINT is the first broad use of functional MRI as part of a psychiatric treatment cleared by the US Food and Drug Administration.²

Bentzley identified 2 primary target populations: those with treatment-resistant depression who have failed multiple antidepressants, and those for whom speed of recovery is clinically urgent due to acute severity. He cited a large insurance claims analysis showing that fewer than 1% of patients who had failed 2 antidepressants received TMS in the subsequent 18 months, framing awareness and access as the field's most pressing implementation challenges. He noted that SAINT has been granted Medicare new technology add-on payment status, enabling access for a substantial proportion of current patients, with commercial payer coverage expanding.

Dr Bentzley is a psychiatrist, neuroscientist, and founder and chief medical officer of Magnus Medical.

References

1. Adepoju OE, Kim LH, Starks SM. Hospital length of stay in patients with and without serious and persistent mental illness: evidence of racial and ethnic differences. Healthcare (Basel). 2022;10(6):1128

2. FDA clears SAINT rapid-acting brain stimulation approach for those suffering from resistant major depression. Brain and Behavior Research Foundation. September 15, 2022. Accessed May 16, 2026. https://bbrfoundation.org/content/fda-clears-saint-rapid-acting-brain-stimulation-approach-those-suffering-resistant-major