Transcranial Magnetic Stimulation (TMS) for depression is typically administered once a day for 20 minutes, 5 days a week for 6 weeks, followed by a gradual taper over the next 3 weeks. Another alternative is to continue for 7 weeks and 1 day to get all 36 sessions as a study comparing this with the taper showed equal efficacy and shortening the protocol almost 2 weeks. This is known as the DASH protocol. The TMS DASH protocol, approved by the FDA in 2016 for Transcranial Magnetic Stimulation (TMS) treatment of depression, is a shorter and more time-efficient alternative to the original, longer standard protocols, reducing session times from approximately 37.5 minutes to 18.75 minutes by utilizing shorter inter-train intervals (ITIs) At TMS of Knoxville we have a 57% remission rate utilizing this treatment.
In 2020, Dr. Nolan Williams at Stanford University School of Medicine, introduced a rapid 5 day protocol called the Stanford Accelerated Intelligent Neuromodulation Technique (SAINT) or, alternatively, the Stanford Neuromodulation Technique (SNT).
How is SAINT performed?
The SAINT method is a type of accelerated TMS protocol that administers a full course of treatment—50 sessions—over the span of just 5 days. Patients undergo 10 sessions per day lasting ten minutes each, separated by 50-minute breaks, and each session utilizes “intermittent theta burst” (iTBS) stimulation to deliver high-frequency pulses over a short duration. iTBS delivered for 3 minutes and 10 seconds has equal efficacy to the DASH 19 minute protocol. Some but not all insurance companies will pay for iTBS.
The brain area targeted by all variants of TMS is the dorsolateral prefrontal cortex (DLPFC), but SAINT utilizes a specific brain-imaging technique called resting functional MRI (fMRI) to localize this region more precisely, which can vary from person to person by as much as several millimeters. This neuronavigation technique makes SAINT more expensive and resource-intensive to deliver (requiring specialized software and technicians) and is unavailable in the Knoxville, TN area, yet it is also thought to increase its accuracy and effectiveness compared to conventional TMS.
What are the results of SAINT TMS?
Two large-scale studies have been published on the SAINT protocol. The first study, published in April 2020, included patients who previously failed to respond to conventional TMS and found that 90% (19 of 21 participants) achieved remission in as little as 3-5 days. The follow-up study, published in October 2021, excluded patients previously treated with TMS but confirmed the strong results, with 79% of 29 participants achieving remission within 5 days of treatment.
The FDA officially cleared the SAINT Neuromodulation System for the treatment of depression in September 2022. Although functional neuronavigation is a required element of the official SAINT protocol studied at Stanford, similar protocols can still be delivered using standard brain mapping techniques rather than fMRI-guided targeting, which has yet to be proven as the primary driver of SAINT/SNT success. All the other ingredients of SAINT—namely, high-frequency iTBS dosing, a greater number of sessions (50 vs 36), and a denser treatment course (1 week vs 6-8 weeks) can be readily applied using conventional TMS machines and standard DLPFC-localization techniques. No insurance in Tennessee currently covers this accelerated protocol.
The 1-day treatment with medication priming
Dr. Cook is the medical director of the Mental Health Association’s annual Fall Psychiatric Symposium, one of the largest continuing educational conferences in the Southeast. He and his TMS Coordinator are members of the Clinical TMS Society and attend annual meetings where they met Jonathan Downar, M.D., Ph.D. from Toronto, an internationally known TMS researcher. We invited Dr. Downar to speak on two occasions. In the 2024 annual meeting, Dr. Downar had a talk on Advances in TMS therapy and discussed a one day protocol. At the time he asked us not to discuss it as it was not currently in print. Six weeks later it was published prior to being peer-reviewed. At the 2025 Clinical TMS Society meeting this year June 13-14, Dr. Downar presented more data about this and there were several other posters and presentations about this protocol. It begins with having the patient take 2 medications 1-2 hours prior to receiving a total of 20 iTBS treatments in 1 day separated by 50 minutes. The medications are Vyvanse 20mg (lisdexamfetamine), a popular amphetamine-based long-acting ADHD stimulant and d-cycloserine 125mg, an old anti-TB drug. Research shows that these medicines enhance synaptic plasticity (essentially rewiring/reconnecting nerve cells). Curiously unlike the SAINT protocol which showed remission at 5 days, the One Day protocol took another 3-6 weeks before remission but had a 73% remission rate by 6 weeks. Our friend and colleague Charles Hayden, M.D. of TMS Huntsville (Alabama) has done several of these treatments and offered assistance in securing the d-cycloserine which has to be compounded and can be fairly expensive. He spaced it out to 2 days due to the grueling schedule with the same results. We are hoping to offer this treatment in the near future if we can secure the d-cycloserine. Unfortunately insurance will not pay for this advanced treatment yet. Seromycin was the pharmaceutical brand name of d-cycloserine but was withdrawn due to newer effective anti-tuberculosis drugs.
