(BPT) - For millions of people living with major depressive disorder, finding an effective treatment can feel like a never-ending process of trial and error — with no guarantee of relief. Although depression is one of the leading causes of disability worldwide, the most common first-line approach, talk therapy combined with medication, frequently falls short.
The problem with this approach is that the first medication prescribed works only about 30% of the time, with the likelihood of success dropping with each subsequent attempt — to under 7% by the fourth medication. Meanwhile, patients continue to suffer debilitating symptoms, endure negative side effects from the medications and, in some cases, remain at a heightened risk of suicide.
In the early 1990s, Medical University of South Carolina (MUSC) psychiatrist and neurologist Mark George, M.D., pioneered a more effective, noninvasive approach: transcranial magnetic stimulation, or TMS. Considered the birthplace of clinical TMS for the treatment of neuropsychiatric disorders, he was instrumental in TMS receiving Food and Drug Administration (FDA) approval in 2008. George's TMS work continues today, now spanning research in obsessive-compulsive disorder (OCD), pain management and smoking cessation.
"The brain is an electrochemical organ," explained Baron Short, M.D., medical director of MUSC Health's Brain Stimulation Service. "In people with major depressive disorder, there are usually parts of the brain that are underactive. With TMS, we produce an electromagnetic pulse that we apply to the top left part of the head. That pulse reactivates the part of the brain that's underactive, leading to a resolution of depressive symptoms."
Typically, TMS treatments are administered in 20-minute sessions over the course of several weeks, for a total of 30 to 36 treatments. Real-world data suggests that TMS leads to complete remission of depression in 62% of patients, with an 83% response rate — defined as at least a 50% reduction in symptoms.
"People tend to start feeling better at about week four, although many people feel better much sooner," said Short.
In 2024, MUSC Health became the first hospital system to offer a revolutionary new depression treatment to patients, taking a successful innovation a leap further. Stanford Neuromodulation Therapy, or SAINT, is a next-generation approach that is fundamentally changing how severe depression and suicidal tendencies can be treated. This dramatically accelerated form of TMS brings patients out of depression in a matter of days — not months — offering rapid relief for people whose severe depression has gone untouched by drugs or psychotherapy.
Building on decades of TMS research at MUSC and countless late-night conversations about how to move the frustratingly slow needle on the treatment of depression, two neuropsychiatrists who trained under Short and George at MUSC, Nolan Williams, M.D., and Brandon Bentzley, M.D., Ph.D., developed SAINT while at Stanford, and it is fundamentally changing how severe depression can be treated.
Rather than delivering treatment over several weeks, the SAINT protocol condenses therapy into five days, with patients undergoing 10 sessions per day. By taking "a video of the brain" using a functional MRI (fMRI) scan and analyzing the data through eight hours of machine learning, physicians can pinpoint the area of the dorsolateral prefrontal cortex that requires stimulation for each patient, personalizing the treatment with precision targeting by sending an electrochemical signal to the exact location.
The results have been striking: remission rates of 80% by day five, with an average time to remission of only 2.6 days and an overall 80% to 90% remission rate for treatment-resistant depression. With treatments of 10 minutes each hour, patients feel a tapping sensation on their heads. They then rest for the remaining 50 minutes before the next round. Generally mild and short-lived, side effects include minor discomfort at the treatment site and muscle twitching.
"Think of it like an exercise," said Short. "If you were going to build your biceps, you wouldn't do 50 curls at once. You would do a set of 10 and then rest. SAINT is like that, but it's very targeted."
Short is encouraged by the results seen with SAINT as well as its future potential. Expanding access to this accelerated approach to depression treatment has become a key focus of his work.
"We see people recover extremely quickly, thanks to SAINT, which has a dramatically higher remission rate for depression than previous treatment options. People wake up out of that mask of depression so they can reengage the world with new vigor and life," he said.
"I have been involved in well over 18,000 TMS and SAINT treatment sessions. It's really rewarding to be a part of that. Why would we make people try inferior treatments and spend months of their lives in agony when you can get them out of depression in a matter of days?"
One challenge he is working to address is limited insurance coverage, which is currently available primarily through Medicare and select insurers.
Baron explained that major depressive disorder remains one of the few serious medical conditions that is still not treated with the urgency of illnesses such as cancer or heart disease. He stressed that it's not simply "feeling down." Rather, the condition is characterized by persistent and debilitating symptoms that include insomnia, difficulty concentrating, appetite changes, a decrease in energy and loss of interest in life that last not days or weeks – but months or even years. It can escalate, he warned, to thoughts of suicide.
A relaxed approach to its treatment, he said, is not acceptable.
"We know 25% of people with major depression will try to commit suicide, and somebody commits suicide every 40 seconds," he said. "We now have more tools than talk therapy, medications that may not work and electroconvulsive therapy, which can be an intimidating procedure for patients. It's critical that we start treating depression as the emergency it is so we can actually do something about it. SAINT enables us to do that. It's like we've been given the keys to the kingdom."
Short explained that SAINT also has the potential to treat other mood disorders, as many of them also find their roots in underactive or overactive areas of the brain.
"SAINT TMS offers intelligent, individualized treatment with unparalleled, fast recovery for patients," he said. "I believe this will change the trajectory of how we treat the depression epidemic."
