Summary: Stanford accelerated intelligent neuromodulation therapy (SAINT), an intensive and individualized form of transcranial magnetic stimulation, produced rapid reductions in depressive symptoms in a controlled trial. Nearly 80% of participants who received the active therapy achieved remission that persisted for months after treatment.
Source: Stanford
An innovative magnetic brain stimulation protocol produced rapid remission for almost 80% of people with severe, treatment-resistant depression in a Stanford University School of Medicine trial.
The procedure, known as Stanford accelerated intelligent neuromodulation therapy (SAINT) or Stanford neuromodulation therapy (SNT), is an accelerated, individualized version of transcranial magnetic stimulation (TMS). In this randomized, double-blind study, most participants experienced symptom relief within days, and many remained well for months. Reported side effects were mild and short-lived, primarily fatigue and headaches.
“It works well, it works quickly and it’s noninvasive,” said Nolan Williams, MD, assistant professor of psychiatry and behavioral sciences and the study’s senior author. The trial results were published Oct. 29 in the American Journal of Psychiatry.
Twenty-nine adults with treatment-resistant depression took part in the trial. About half were assigned to receive active SAINT therapy and the remainder received a carefully designed sham procedure that simulated the experience without delivering therapeutic stimulation. After five days of treatment, 78.6% of the participants in the active group met criteria for remission based on standard clinical scales. Co-author Alan Schatzberg, MD, described the results as “quite a dramatic effect” that was “quite sustained.”
A lifetime of depression
One participant, 60-year-old Tommy Van Brocklin, had experienced depression since his mid-teens. Over decades he tried talk therapy and multiple medications, including selective serotonin reuptake inhibitors that initially helped but eventually lost effectiveness. After many unsuccessful trials of medications and treatments, Van Brocklin was referred to the Stanford study by a relative. He traveled from Memphis to receive the SAINT protocol in September.
He reports that nothing changed on the first day, emotional processing began on the second day, and by the third day he felt a clear and lasting improvement. “It broke through,” he said. “I felt so much better, and it’s stuck with me.” Since returning home he says he sleeps better, stopped drinking, enjoys playing guitar again and feels motivated to rebuild his life.
What makes SAINT different
Standard FDA-approved TMS for depression typically requires daily sessions over six weeks and produces remission in roughly one-third of patients. SAINT modifies this approach in two key ways: individualized targeting based on each person’s brain connectivity, and a higher total pulse dose delivered over a condensed timeframe.
Before treatment, researchers obtained resting-state MRI scans to identify the precise spot in each participant’s left dorsolateral prefrontal cortex (DLPFC) that is most anticorrelated with the subgenual anterior cingulate cortex—a region often overactive in depression. Targeting the DLPFC subregion with the strongest functional relationship to the subgenual cingulate aims to strengthen regulatory connections and reduce pathological activity.
The team delivered 1,800 pulses per session—three times the amount used in some standard protocols—and provided ten 10-minute stimulation sessions each day with 50-minute breaks between sessions. That accelerated schedule compressed a weeks-long treatment course into five consecutive days of intensive therapy. Higher pulse counts have been used safely in other neuromodulation contexts, such as treatments for Parkinson’s disease.
For the sham group, the investigators used a coil that mimicked the sensation and sound of active stimulation. All participants wore noise-canceling earphones and received a topical anesthetic to reduce scalp sensation. The study was double-blind: neither the participant nor the clinician administering the sessions knew whether the treatment was active or sham.
Participants and outcomes
Participants were adults aged 22 to 80 who had experienced depression for an average of nine years and who had not responded to prior treatments. During the trial, participants continued any stable antidepressant medications but did not begin new medications.
Four weeks after treatment, 12 of 14 participants in the active group showed clinical improvement and 11 met FDA criteria for remission. In contrast, only two of 15 participants in the sham group reached remission. The active group’s mean reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score four weeks after treatment was 52.5%, compared with 11.1% in the sham group.
Because many participants reported symptom relief within days, the researchers suggest SAINT could be particularly useful for rapidly treating people in psychiatric crisis or in the high-risk period immediately after hospitalization—situations in which conventional antidepressant medications often take weeks to produce benefit.
Williams noted the potential to implement this accelerated protocol in emergency departments and psychiatric wards to reduce suicide risk during acute phases of illness.
Van Brocklin’s experience illustrates the personal impact some patients may achieve: improved sleep, renewed motivation, cessation of alcohol use and restored enjoyment of everyday activities. He emphasized that these changes have been meaningful and sustained since his treatment.
About this depression research news
Author: Mandy Erickson
Source: Stanford University School of Medicine
Contact: Mandy Erickson – Stanford
Image: The image is in the public domain
Original research: Closed access. “Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial” by Eleanor J. Cole et al., American Journal of Psychiatry.
Abstract
Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial
Objective:
Depression is a leading cause of disability worldwide, and about half of people with depression experience treatment-resistant forms of the illness. Intermittent theta-burst stimulation (iTBS) is an FDA-approved TMS approach for treatment-resistant depression but is limited by modest effectiveness and a six-week course. The investigators developed a neuroscience-informed accelerated iTBS protocol—Stanford neuromodulation therapy (SNT), formerly called SAINT—to address these limitations. An earlier open-label study showed an approximately 90% remission rate after five days; this report summarizes results from a sham-controlled, double-blind trial.
Methods:
Adults with treatment-resistant depression experiencing moderate to severe episodes were randomized to receive active or sham SNT. Resting-state functional MRI guided individualized targeting of the left dorsolateral prefrontal cortex region most anticorrelated with the subgenual anterior cingulate cortex. The primary outcome measure was MADRS score at four weeks after treatment.
Results:
At the planned interim analysis, 32 participants had been enrolled; 29 continued to meet inclusion criteria and received either active (n=14) or sham (n=15) SNT. Four weeks after treatment, the active group showed a mean reduction in MADRS score of 52.5% from baseline versus 11.1% in the sham group.
Conclusions:
SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation in this trial for treatment-resistant depression. Additional research is needed to determine the long-term durability of effects and to compare SNT with other depression treatments.