A Q&A with Dr. Mark S. George on Brain Stimulation for Psychiatric Illness

Q&A with Mark S. George, M.D.

Distinguished Professor of Psychiatry, Radiology and Neuroscience

Founding Director, Center for Advanced Imaging Research

Director, Brain Stimulation Laboratory, Psychiatry

Medical University of South Carolina Member,

BBRF Scientific Council

2008 BBRF Falcone Prize for Outstanding Achievement in Affective Disorders Research

1998 BBRF Independent Investigator grant

1996 BBRF Young Investigator grant

For someone reading this today who suffers from depression and wants to try TMS, what’s the best way to go about it? How do you find a reliable place for treatment?

Today, almost every reasonably sized city in the U.S. has a couple of different providers. There are different ways that it’s being provided. There are national chains that provide the TMS; your psychiatrist can refer you to one, kind of like a dialysis center or an imaging center. But maybe the easiest and most reliable approach would be to look up the Clinical TMS Society (https://www.clinicaltmssociety.org) It’s a national organization of psychiatrists who do TMS and their standards are high. They have a lot of information on their website about local providers. That’s how I would do it.

Are there any “best places” you can recommend for TMS treatments?

The thing that’s important about TMS is that years ago, we did the studies, we found the effect, and then we had to figure out a way that we could train psychiatrists how to do it. And we did. And so, most psychiatrists who have gone to a week-long training course, like one we offer here in Charleston, get results that are just as good as you would get at a major medical center. As long as the doctor has been well trained, the results tend to be good. And that’s important to me because people are always calling up and saying, “We want to come to Charleston to have you do it.” I say, “Look, it is so much better for you to see a local doctor—they will do just as good, and maybe better, because you won’t be living in a hotel, be displaced and stressed while you’re getting your treatments.” So again, the Clinical TMS Society is probably the best first step.

You spoke about some of the future potential uses for TMS. Are those available for people now? Do these have to wait for FDA approval?

I’m pretty conservative clinically while I push the limit as a researcher. And I tend to be evidence-based. When you ask for things that aren’t yet FDA-approved, it becomes an individual discussion with your doctor about the risk and benefits. And I think that’s appropriate if the discussion is good and the evidence is there. But for those applications that aren’t yet approved, it’s really important to go to somebody who’s well trained and who will give you an honest answer about what the evidence and risks are. It’s likely that TMS is pretty risk-free. The side effects are minimal. But it’s best to go to somebody who’s well trained and has some experience.

Could you tell us a little bit more about the side effects of TMS that people may sometimes experience?

TMS is loud, so you have to wear ear plugs. People often feel a tapping sensation when the treatment is delivered, as the coil is placed against the scalp. Common side effects include minor headaches which usually go away after the treatment is over; also, transient scalp discomfort at the site where treatment is given, and sometimes, twitching of facial muscles, again. while the treatment is being given. In very rare cases, TMS can cause a seizure. Another rare impact in some people with depression is that they may feel a little elevated by the treatment—what we call hypomania.

Is it one course of treatment—or may some patients need ongoing “boosters”?

For the treatment of depression it’s a rule of thirds. If you have treatment-resistant depression—for example, you have tried and failed two medications—then your chance of having a remission with TMS (full relief of symptoms, at least for a time) is one-third. For your symptoms to be reduced by half there is also a one-in-three chance. Finally, there’s a one-in-three chance you won’t have any benefit. After an initial course, for patients who responded or had a remission, there’s another rule of thirds. One third of people who’ve remitted will never need TMS again after a single course. They may stay on medications. They may do talk therapy. But they’ve changed. They’ve gotten out of that hole. Another third will need another TMS course within two years. Another third will go a couple of months before they relapse and they’ll need another full treatment course. Those patients will also probably need what’s called “maintenance,” where we work out doing treatments once a week, or once every couple of weeks for them.

Is there a way to predict which group you are going to be in?

No, but we would love that. And it’s part of the research that we’re doing here. I’d love to have a sorting hat like in Harry Potter where we can predict who will respond or not. Research with brain imaging or genetics or a combination of both shows some promise in this area.

Could you tell us a little bit about the portable version of TMS that you’re working on?

The question is, can you actually have at-home devices to deliver TMS. TMS requires a large capacitor and it might cause a seizure, so it is not easy to be made into a home-based treatment. But another less invasive approach shows promise. We’ve just finished a study of a taVNS device— transcutaneous auricular VNS—which is used at home for people with “long COVID” and depression. It looks like it might work and if it does, it will mean the patient never has to come in. [taVNS non-invasively delivers electrical stimulation to the auricular branch of the vagus nerve, an easily accessible target that innervates the human ear.] We send the device to you. We do everything online. So that’s a possibility. Then we have another device (Neurolief) that’s in a pivotal clinical study. If this study is positive, it could be on the market in a year. It actually stimulates the trigeminal nerve and the occipital nerve. You would wear this device twice a day for 20 or 30 minutes. The study is in progress right now.

Can you speak about the extent to which research is being conducted with adolescents, 15- to 18-yearolds, and whether there are any cautions you have regarding this age-group?

I’m sympathetic. I think the earlier in life that we can make an intervention, the greater the potential is for lifelong improvement. And the brain is more plastic early in life and should be easier to change with brain stimulation. Yet TMS for adolescent depression is not yet FDA-approved. The problem is that it’s hard to study adolescent depression.

Clinically, I have good reason to think that TMS works to treat adolescent depression. I have had many clinical patients who were students who got depressed, dropped out of school, isolated at home. And then we treated them with TMS and they get a lot better. They get back on their game. Years later they send me graduation pictures from college or wedding pictures. And it’s so heartwarming because I think the brain is more plastic in adolescence. And so, the chances of moving the circuits involved in depression and actually changing the lifelong trajectory of depression are really good. It’s not FDA-approved yet for this group, but we do it in my practice and find that it works. But this is still a gray zone and as I said, studies are hard to do.

Could you speak a little bit about the suicide prevention aspect of TMS, because that’s obviously an important issue.

We need good, quick treatments for suicidality. The last two years have shown potential promise with ketamine, which is rapid-acting. We know that ECT works, but ECT has to be done on an inpatient basis. I refer back, then, to the research on accelerated and intensified TMS that my former student, Dr. Nolan Williams, has just done, which is so important. His 5-day course of accelerated TMS gets people un-suicidal often within a day or two. The accelerated TMS approach that Dr. Williams is using hopefully will be available in the period just ahead. Ketamine certainly is already making a difference. Researchers now are putting TMS machines in psychiatric emergency rooms. There are so many people who now come to an emergency center who are terribly depressed and suicidal and they can’t get a bed in a timely fashion. And so they spend two to three days waiting in the emergency room to get into the hospital. If we have TMS machines there and we can start treating, they may actually not even need to be admitted. So I’m excited that we could have treatments either like ketamine or TMS, or both, that can get quick resolution and then get people on the road to recovery.

Written By Peter Tarr, Ph.D.

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