KELLIE NEWSOME: Call it SNT. Call it SAINT, but who do you call when your patient needs this intervention for depression? Welcome to The Carlat Psychiatry Podcast, keeping psychiatry honest since 2003.

CHRIS AIKEN: I’m Chris Aiken, the editor-in-chief of The Carlat Report.

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

CHRIS AIKEN: Last week, we learned that SNT TMS brings 80% of patients to full remission even after 3-7 failed antidepressant trials. But we still have questions.

1. How does it work?

2. How long does it last? 

3. How do you find it for your patients?

KELLIE NEWSOME: TMS uses magnetic pulses to change the electrical rhythms of the brain. That’s called neuromodulation. If you want a more poetic version of that, rewind to our November 3rd episode, where Owen Muir compares it to music, good memories, and psychotherapy. All of these things change the brain’s rhythm in ways that change us, that can lead to new learning. And learning is what the brain is doing in TMS – it’s learning how to not be depressed, or not have OCD, or not want to smoke cigarettes anymore. So when Nolan Williams set out to improve on this treatment, he looked back on how he learned as he crammed for college exams.

NOLAN WILLIAMS: We’ve known for some time, based on spaced-learning theory, that you can’t load a bunch of information into the brain without breaks. The brain needs downtime to produce proteins, strengthen dendritic spines, and create longer-term effects. And so, there has been basic science experiments have shown that you need about an hour to an hour and a half between each application of stimulation. This also shows up in learning experiments. If you take someone and you show someone something, wait about an hour, and then show it to them again, the effect is much stronger than if you show it twice in a row within the same period. We intuitively know this. If you’ve ever studied for hard tests in college, grad school, or med school, what you learn is that you can’t make a single notecard and look at it 50 times and then stop. You need to make 60 notecards, look at each one for a minute, and then you get back to the first one an hour later because they really need time to re-experience it. And we know that stimulation can recapitulate this finding. If you wait only 15 minutes, you get really get no change in cortical excitability; you have to wait longer to see that. That’s the rearrangement in timing that we worked on and built the engineering around.

KELLIE NEWSOME: By keeping the interval between treatments at one hour, Williams was mirroring the way that people learn, both at a psychological level and at the level of the neuron. It takes about an hour for the neurons to produce the proteins it needs to change in response to the magnetic pulses of TMS, a process called long term potentiation. We spoke with Brandon Bentzley, who helped develop SNT:

BRANDON BENTZLY: One of the ways to really match that peak to the protein expression so that you can actually build on potentiation is to do about an hour spacing. There's some wiggle room there. Yeah, you could do 90 minutes, but at that point, target all the stimulation of the day. On the earlier end, maybe 40, I think even 30 would be probably cut on the early side, but then you run into a situation where you're not really optimizing it. So, we chose the peak of that, so we can say, okay, well, you can fit in 10 sessions in a 12-hour shift, which is what technicians worked in the lab.

CHRIS AIKEN: Long-term potentiation is the building block of neuroplasticity, and it’s triggered by the TMS pulses: Remodeling dendrites, strengthening neuronal connections, and increasing their sensitivity to neurotransmitters. At a cellular level, it means the neurons are communicating better; at the patient level, your patient is likely to say that they are thinking clearer. TMS is not the only therapy that operates through long-term potentiation. We also see it with psilocybin, lithium, cognitive behavioral therapy, and aerobic exercise.

KELLIE NEWSOME: Let’s pause for a preview of the CME quiz for this episode. Earn CME for each episode through the link in the show notes. 

1. In a small clinical trial, what percent of patients stayed in recovery from depression after SNT TMS, using as-needed maintenance treatments?

A. 20%

B. 50%

C: 80%

D: 100%

CHRIS AIKEN: Back in 2020, I interviewed Joe Goldberg, and he pointed out that we really don’t know what to do for patients with high levels of treatment resistance – after, say, five or more antidepressants have failed. At that time, we had no placebo-controlled trials to guide us. SNT TMS changes that, but how long do its benefits last? The Stanford group is currently at work testing whether they can keep people well by delivering brief, one-day treatments of SNT TMS on an as needed basis. The “need” here is determined by biometric monitoring. They created a kind of deluxe Fitbit that measures daily steps and more: heart rate, temperature, movements, sleep, and activity patterns. These things correlate tightly with depression ratings, so it’s like getting a daily mood rating without any effort from the patient. If they see early warning signs of depression, they invite the patient in for a TMS booster. So far, they’ve published one study of this approach. It lasted a year, enrolled 21 patients, and 100% of them stayed well with as needed SNT TMS. On average, they required a booster treatment about one day every month.

KELLIE NEWSOME: This is all good news for difficult-to-treat depression, but how do you bring SNT TMS to your patient? New SNT centers are opening up every month, and you can find the updated list at MagnusMed.com. As of November 2025, it is available in New Orleans, Louisiana; Coral Springs, Florida; Charleston, South Carolina; Charlotte, North Carolina; New York City, Iowa City, Little Rock, Arkansas, Seattle, Washington, and in seven California cities near San Diego, Los Angeles, and San Francisco.

CHRIS AIKEN: But you don’t need to send everyone with difficult-to-treat depression to SNT. When antidepressants don’t work, consider regular TMS first; it’s about twice as effective as augmentation with other meds like aripiprazole. And regular TMS is more accessible than SNT TMS. If the six-week treatment is too long, the FDA has just approved an accelerated protocol with Brainsway’s Deep TMS, and it lets patients cluster most of the treatment sessions in the first week, followed by a few treatments that are spaced out so they don’t have to take significant time off of work. This accelerated Deep TMS is like a mini version of SNT TMS, and while the data looks good, it’s not as strong as SNT and hasn’t been tested in as high a degree of treatment resistance. I mean, the treatment itself is probably not as strong or potent as SNT, the data is still solid. This FDA approval just came out, so it will take time for insurers to start reimbursing accelerated deep TMS.

DANIEL CARLAT: Hello?

NOLAN WILLIAMS: Hello.

DANIEL CARLAT: Yeah, this is perfect. Okay, let's talk about psychiatry 3.0.

NOLAN WILLIAMS: Yeah, so typically when I see a patient, they have usually failed everything. In my view, they clearly have a circuit disorder that's locked in to the brain.

KELLIE NEWSOME: That was Danny Carlat calling Nolan Williams in 2015 for his first Carlat interview. On that call, Dr. Williams laid out the case that we are entering Psychiatry 3.0, where version 1.0 was psychoanalysis, 2.0 was pharmacotherapy, and version 3.0 is neuromodulation, the ability to change behavior with magnetic pulses that re-sych brain rhythms and reshape neural connections. 

CHRIS AIKEN: Neuromodulation is a new method, but it has a PR problem. We touched on that in our interview with Owen Muir two weeks ago. At best, TMS is hard to understand; at worst, it is science fiction. And we recently lost one of its biggest proponents. As we were in the middle of this podcast series, Dr. Williams passed away on October 8, 2025, at the age of 43. He didn’t just lead the research. He tried to bring it within reach, a frequent guest on podcasts and TV shows, speaking to healthcare systems across the world and to insurers in the US to SNT TMS covered.

KELLIE NEWSOME: Nolan’s family announced the cause of his death in the New York Times obituary. It was a preventable one, something that takes the lives of 1 in 8,000 physicians every year, and something that Nolan worked hard to prevent: Suicide.

CHRIS AIKEN: Nolan touched many lives, as the many tributes from patients, friends, colleagues, and students online testify. Besides TMS, he ran psychedelic trials of ibogaine for traumatic brain injury and addiction in veterans. His latest project was on hypnosis. He found that only 1 in 5 people are highly hypnotizable, and Nolan thought we could learn from them, especially if we’re trying to change habits that are hard to break, like smoking. He found that TMS could induce hypnotic states, bringing the treatment back to Psychiatry 1.0, as he would have put it, when Freud discovered psychoanalysis through his forays into hypnosis.

KELLIE NEWSOME: Nolan left behind a wife and two children and many students, colleagues, and patients. You can support his legacy at nolanrwilliams.com. One of Nolan’s goals was to make SNT TMS available in the hospital, something we haven’t achieved yet – it is only covered as an outpatient treatment in a hospital-type setting, kind of like coverage for a partial hospital program. Nolan often began his lectures by commenting on this problem:

NOLAN WILLIAMS: So in psychiatry, the patient comes into the outpatient psychiatrist's office and says, “I've been thinking about ending my life. I've been researching ways to do it.” And so what does the psychiatrist do? Politely steps out of the room, calls the police. The police come, they handcuff the patient, put them in the back of a squad car, and drive them to the emergency room. And then they're strip-searched and placed in a hall bed waiting for a psych bed in a psych unit. Right? And then when they get up there, they're told we don't have any additional treatments for you beyond what was available as an outpatient. Unlike the rest of medicine, in psychiatry, as you escalate the acuity of care, we can get into details, but on average, you lose treatment options, and there are no tests, and what's even more striking is that your suicide risk at discharge is triple what it was for the rest of your life.

CHRIS AIKEN: That was Nolan in 2023. In one of his final media appearances, on May 20, 2025, with the Alan Hu Foundation, he told the same story, but this time it had a more personal edge to it….

NOLAN WILLIAMS: If you're seeing your psychiatrist saying that you want to end your life, you end up being in a scenario where they, too, call the authorities, but instead of the ambulance coming to pick you up, you end up in the back of a squad car, at least in the state of California.

CHRIS AIKEN: As I thought about Nolan, I realized that many trailblazers who changed psychiatry struggled with the same mental problems in themselves or their close family. Including Owen Muir, who is open about having bipolar disorder and whose own recovery from depression with accelerated TMS led him to work on the controlled trial that got the new FDA label for accelerated Deep TMS this year, the protocol that speeds up the therapy by starting with 4 treatments a day.

OWEN MUIR: For people who've lived with a specific kind of suffering, what you understand about your own suffering is likely to be different than what other people notice from the outside, which can lead to research questions that other people wouldn't come up with. And so you have the dual motivation of knowing what it's like to suffer, and knowing something about how it might be better. And so it may be that individuals who've lived through suffering are more motivated and more capable of asking the most interesting questions. They may be more willing to place the huge bet of years to decades of their life on the answer to that question. And so I suspect those who have, you know, what we call lived experience, might be actually the best people to answer questions if they happen to like research or be willing to subject themselves to clinical research. We'd want every researcher to have a unique insight. We want everyone to be relentless in the work that they do, but people who've lived it know it can't wait.

CHRIS AIKEN: We’ll pick up there next week, that inspired other psychiatric revolutions, like psychoanalysis, 12-step programs, lithium, light therapy, DBT, and even The Carlat Report.

KELLIE NEWSOME: Dr. Aiken’s new book, Difficult to Treat Depression, is now available in print and as an audiobook, and it covers three strategies that boost TMS’s antidepressant effects by pairing it with cycloserine (a glutamatergic med that enhances learning), light therapy, or CBT. You’ll discover other novel therapies like celecoxib, minocycline, probiotics, how to use them, and how to deprescribe the ones that aren’t working.

CHRIS AIKEN: Audio excerpts in this podcast are from Nolan Williams' lecture at the Mental Healthcare Innovations Summit, his interview with the Alan Hu Foundation, and from Carlat Report interviews with Nolan Williams, Brandon Bentzley, and Owen Muir.