Mind Dive

Episode 56: Magnetism & Depression Treatment with Dr. Neil Puri

• The Menninger Clinic

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Dr. Neil Puri is at the forefront of combating treatment-resistant depression, spearheading new ways to use brain stimulation treatment to offer relief to patients. Building off recent advancements in transcranial magnetic stimulation, Dr. Puri’s team is using focused bursts of electromagnetism to rewire individual neural pathways in the brain. Dr. Puri explains how this tailored approach allows for treatment plans unique to the patient and has resulted in unprecedented levels of success with patients for whom traditional depression treatment plans have not been effective.  

This episode of Menninger Clinic’s Mind Dive Podcast features one of our own, Dr. Puri, an accomplished psychiatrist and director of Menninger’s Center for Brain Stimulation joining hosts Dr. Kerry Horrell  and Dr. Bob Boland for a behind the scenes look at fMRI-guided transcranial magnetic stimulation and how it can be a game changer for patients with treatment-resistant depression.  

Dr. Puri is the medical director for both the Adult Division and the Center for Brain Stimulation at the Menninger Clinic and is an assistant professor at Baylor College of Medicine. He is board certified in psychiatry and earned his medical degree and undergraduate degree at Northwestern University.  

“Our conventional treatments only go so far, only about two-thirds of individuals will achieve relief,” said Dr. Puri. “We need cutting edge treatments to disrupt the treatment field of depression so we can find new ways to treat those one-third of people who are unable to benefit from traditional treatment.”  

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Visit The Menninger Clinic website to learn more about The Menninger Clinic’s research and leadership role in mental health.

Dr. Bob Boland:

Welcome to the Mind Dive podcast brought to you by the Menninger Clinic, a national leader in mental health care. We're your hosts, Dr. Bob Boland and Dr. Kerry Horrell. Twice monthly.

Dr. Kerry Horrell:

We dive into mental health topics that fascinate us as clinical professionals and we explore those unexpected dilemmas that arise while treating patients. Join us for all of this, plus the latest research and perspectives from the minds of distinguished colleagues near and far. Let's dive in.

Dr. Bob Boland:

We're very excited because we have someone who we've been trying to get on for quite some time. I know exactly he's in high demand, so we're very thrilled that he took some time to meet with us. This is Dr Neil Peary. Dr Peary, he's the medical director here at Menninger for the Outpatient Division. He's also the medical director of our Center for Brain Stimulation in Menninger 360. In addition, he's an assistant professor in the Menagerie Department of Psychiatry and Behavioral Sciences at the Baylor College of Medicine Board. Certified in psychiatry, dr Perry earned both his bachelor's degree and medical degree from Northwestern University in Chicago. He completed a residency in psychiatry at the University of Pittsburgh and a fellowship at George Washington University in Washington DC.

Dr. Kerry Horrell:

Thanks so much.

Dr. Neil Puri:

We really appreciate your coming.

Dr. Bob Boland:

All right. So we're going to start, though, with the question we usually ask people, and just tell us a little about your career and like how you became interested in what we're going to be talking about today brain stimulation but in everything that you're doing, really.

Dr. Neil Puri:

So I started my career as an attending psychiatrist here at the Manninger Clinic, where I started becoming very interested in treatment-resistant depression, just because I saw the impact it had on our patients, how long people suffered with it, how long they continue to suffer while trying to find the right treatment and the increased suicidality that came with it. While trying to find the right treatment and the increased suicidality that came with it, that sparked my interest in more advanced or interventional or cutting-edge treatments for treatment-resistant depression. For my residency, I had done a lot of electroconvulsive therapy, so I worked in that domain a good bit and it sparked my interest in newer treatments like ketamine, tms, as well as things that are up and coming with things like psilocybin, mdma.

Dr. Kerry Horrell:

Here's a quick question. I'm sorry you might have been in the middle of this. Did we have a brain stimulation center when you started at Menagerie?

Dr. Neil Puri:

No, we did not.

Dr. Kerry Horrell:

And were you on HOPE? Were you on the adult program?

Dr. Neil Puri:

I was on the adult program when I first started.

Dr. Kerry Horrell:

Were you part of who started the Brain Stimulation Center?

Dr. Neil Puri:

I did participate in the starting up.

Dr. Kerry Horrell:

That's exciting, that's really cool, because I feel like this is a huge part of the work we do here, not only, again, for the treatment of patients, but again like bringing this to the country, like bringing out more research and like innovation around this.

Dr. Bob Boland:

We keep talking about brain stimulation. You should probably tell people what brain stimulation is. We were assuming, but I don't know.

Dr. Neil Puri:

So some people call it brain stimulation, other people are now starting to call it interventional psychiatry or neuromodulation. In our center here we offer ECT, electrochemosotherapy, tms, transcranial magnetic stimulation and ketamine.

Dr. Kerry Horrell:

I listeners will know I work on our young adults unit and our young adults who go over to the brain stimulation center. They'll come back and they'll talk about it in groups and it's my favorite thing to hear them talk about it because they do not understand this. They're consenting and they're doing it. But sometimes, like a patient recently said, yeah, I'm doing TMS and the other patients are like what is TMS? And this kid just goes it's like magnets, I think, and like that was his full description of it. So that was like I love that you were listening in the informed consent part of your tms we spent a long time explaining I know you do though they are hard to understand and, I think, for the population you work with.

Dr. Neil Puri:

He probably did a pretty good job explaining he was like it's magnets and stuff that's, I know, many psychiatrists.

Dr. Bob Boland:

That's about as far as they're done, so maybe you'll tell us a little bit more about it though. Yeah, but uh, you know, let's start just like like, with the need, right, I mean yeah, I mean like why? Why do we need more treatments for depression? Don't we have plenty?

Dr. Neil Puri:

we do have lots of treatments for depression, but our conventional treatments only go so far. One could say about only two-thirds of, but our conventional treatments only go so far. One could say about only two-thirds of patients with conventional treatments. Looking at a variety of big, large and by conventional treatments you mean like Medications and therapy, right, sure? So only about two-thirds of those people will achieve relief. That means one-third of people will still have only partial relief or no relief at all, and it takes a long time to even get to those two-thirds. So people can be suffering for months or years to only get a partial response, and people with partial response or no response will just have longer periods of depression, worse overall health outcomes and remain at increased risk for suicidality. So we really need cutting edge treatments. We need to disrupt the treatment field of depression so that we can find new treatments to help those one-third of people that do not get benefit which one-third is a lot.

Dr. Kerry Horrell:

That's way too much, and my guess is that you can tell me if I'm wrong. You might know this too Like of the amount of people you know in the population who have depression and who are getting treatment, if a third of them aren't getting better or they're not getting better as quickly as we'd like them to. I bet that's more than a third of our Menninger patients, like our Menninger patients probably represent a lot of that. Third is my guess.

Dr. Kerry Horrell:

A third of people with depression not getting better we're like the group who are treatment refractory or and actually this is another question I've had which is what makes them a treatment resistant, like what qualifies them for treatment resistance. But that's got to be a lot of the kind of people who end up in inpatient maybe not necessarily, but like that's a lot of folks who it's a lot of the folks who do come through our doors seem like they are saying hey, I've tried other stuff, I tried outpatient, I'm not getting better. I'm feeling really hopeless, I'm feeling at the end of my rope.

Dr. Neil Puri:

So we do see a larger percentage of people who are treatment resistant here at Menninger. Yeah, because that's the reason they're seeking us out. A lot of the people who are going to respond to the first and second line of treatment may have just gotten that benefit from seeing their primary care doctor or the first psychiatrist they met and they feel better and they're on their way, which is what we hope for. But it doesn't work that way and that's why people seek us out and that's why we do have a larger percentage of people who are treatment resistant.

Dr. Kerry Horrell:

I do wonder if you have thoughts and maybe there's something more formalized in this of what makes somebody treatment resistant, like how many of meds would you have had to have tried? What kinds of treatment? Because I actually the reason I say this and this is coming from a little bit of an ornery place is I do have a lot of my young adults being like I have treatment resistant depression and I'm like are you even old enough to have treatment-resistant depression at this point? Then that's not totally fair. But how would you qualify that somebody is considered treatment-resistant or treatment refractory?

Dr. Neil Puri:

So the bar could be set at different levels, sometimes quite low. It's just having done two adequate trials of a medication will start qualifying you Two.

Dr. Bob Boland:

The adequate Adequate. That's the key right, right.

Dr. Neil Puri:

So for a long enough period of time and for a high enough dose so that to get to two adequate trials we're already talking about several months. That's true of depression treatment yeah, that's a good point yeah, last stage is three, though, right.

Dr. Bob Boland:

Yes, yeah, yeah, that was the low one, right is therapy required to have been given like?

Dr. Kerry Horrell:

is that something they have to have given a shot to be considered true?

Dr. Neil Puri:

in my book.

Dr. Kerry Horrell:

Yes, but that's not always, but not necessarily okay, okay well, we were going to focus a little bit on tms today and hear about some of your work specifically in that, as we alluded to, it'd be helpful to hear about what that is yeah, yeah, and just it's magnet, it's the magnet one um, but it has been around for a while. How has it grown like? If you could take us a little bit through what this treatment is, how it's developed sure so?

Dr. Neil Puri:

um, tms has been around since about 2007 in terms of its use in psychiatry, with some of the early trials and fd approvals. That that's not that long. No, it's not, but the technology is pretty old. So, first of all, what does TEMA stand for? Transcranial magnetic stimulation? It's a mouthful, but all that really means is we're putting a magnet transcranially outside of your head.

Dr. Kerry Horrell:

It's the magnet one. It's the magnet.

Dr. Neil Puri:

And stimulating the neurons there. So it's based on old technology and stimulating the neurons there. So it's based on old technology. Metal detectors if you've gone through a metal detector, you've experienced a form of transcranial magnetic stimulation right. An MRI machine if you've had an MRI and your head went inside the tube, you've experienced transcranial magnetic stimulation. The difference between those forms of transcranial magnetic stimulation and what we're talking about in the treatment of psychiatric stories using transcranial magnetic stimulation or TMS, is that the treatment target is very focal. Whereas if you go on MRI it's getting your whole head, if you walk through a metal detector it's getting your whole body Right and the magnetic pulses or the oscillations of the magnetic field, the changing of the magnetic field, is very rapid. Changing magnetic fields we think back to physics. If you did electromagnetism in physics, yeah, I sure did.

Dr. Neil Puri:

I never took physics.

Dr. Kerry Horrell:

Do you remember everything I have not taken a single physics class, but please Changing magnetic fields will produce an electrical field.

Dr. Neil Puri:

So by creating a rapidly changing magnet we're able to induce a very focalized electrical field. We can also produce electrical field with current, like we do with ECT, but that's not that focalized and it goes out from one side of the head to the other and that's what causes seizures. With tms the magnetic field is small, it's focal and only penetrates about like three centimeters deep, so it just gets through the hair, the scalp, the bone and into the gray matter of the brain and doesn't go out the other end and doesn't get deep enough into the brain to cause a seizure I don't think I realized.

Dr. Kerry Horrell:

I mean gosh, I am a great person, explains too, because the amount of me not getting some of this is very high actually. Wait, can I tell a quick story?

Dr. Bob Boland:

okay, a quick story when I was an intern you know, neither of us said yes, but go ahead yeah, well, you didn't stop me either.

Dr. Kerry Horrell:

um, when I was an intern, um, I had come to Menninger for my training and I said to Dr Patty Daza, our training director and psychology director, that I was really skeptical about ECT, tms and some of these. I just was like I don't feel good about it. I was like I feel anxious about it, I don't feel good about referring my patients to that. And she was like, well, it's a big part of what we do here, so you better learn more about it. Why don't you meet with Dr Puri and why don't you? You can ask him some questions. And Dr Puri graciously agreed to meet with me and then also graciously invited me to watch ECT. And I did get to watch ECT, in which I almost passed out, which was kind of embarrassing, because it's not like a particularly scary thing to watch. I just don't do well with small spaces, but that's not the point of the story.

Dr. Kerry Horrell:

The point of the story and this has stuck with me so much, dr perry, I've probably even said this on the podcast before which is I said you said what makes you uncomfortable with it? And I said because we don't know why it helps. And you said well, that's all the psychiatry you. You said that is that's ssri, that's our medication. Like so much of what we do, we do because we see that it helps, not because we know why it helps. And I that has stayed with me and has really impacted me because I was like that's so true, like, and so I think I am interested in the mechanism of change of these things but I don't think I, I really anyone, will totally understand them. I don't think I realized tns was so similar to ect in the change mechanism, but it's electricity well, is it?

Dr. Kerry Horrell:

is that I know and I'm like maybe I'm getting that wrong well it's causing the neurons to depolarize using electrical fields, and that way it's similar.

Dr. Neil Puri:

Okay though, I think, in terms of how it works. At the end of the day, there might be a lot of similarities there, but significant differences too yeah, do you have?

Dr. Kerry Horrell:

this is a really unfair question, but do you have a sense of why it helps?

Dr. Neil Puri:

Yeah. So I think there's a couple of ways we can think about how it helps. One is kind of in a localized fashion, releasing our transmitters, okay. But I think more broadly, what it's doing, it's working on and this is what we're learning a lot about right now in psychiatry. It's working on depressive circuits. It helps the circuits in our brain change and actually we also learn. You know, therapy helps the circuits in our brain change and we're not going to use magnetic fields and you're going to use therapy to help elicit changes to the circuits, right? So when we stimulate one part of our brain, we cause that part of our brain to change, but we also change the way everything else is wired to that part of the brain. That's a bit about how it might work. It's also a bit about how ECT may work and our medication at the end of the day as well.

Dr. Bob Boland:

Yeah, so it's been around for a while, but you're pioneering a new form of TMS. Do you want to say something about that?

Dr. Neil Puri:

but you're pioneering a new form of TMS. Do you want to say something about that? Yeah, so we are pioneering or working with now what is fMRI-guided TMS, and it's given in a rapid format and to an fMRI-guided target.

Dr. Kerry Horrell:

Is there a long name for this?

Dr. Neil Puri:

So I think if we wanted to use a very descriptive scientific name no-transcript fmri guided accelerated prolonged intermittent data burst stimulation yeah, so no one's going at that.

Dr. Bob Boland:

Is there an acronym or something?

Dr. Neil Puri:

our program is called rapid targeted tms. Yeah, really sounds better. Yeah, looking at the fact that it's rapid. Yeah, because this accelerated protocol is done in five days which does sound brutal it's intense, not brutal, painful.

Dr. Bob Boland:

brutal just like the amount of time you'd have to, because this accelerated protocol is done in five days, which does sound brutal it's intense, not brutal, painful, brutal, just like the amount of time you'd have to sit and do TMS Sure, and it's targeted by the FMR. You mean brutal for him? Well, brutal for both, I guess.

Dr. Neil Puri:

Yeah, right For both. Yeah, it's a lot of work, it's a big commitment both from the staff standpoint. It takes 50 hours.

Dr. Bob Boland:

Yeah, well, take a little zoom for us. So what does it actually entail? So you show up and what happens?

Dr. Neil Puri:

All right, so you show up and the first thing is is we're going to get an fMRI. So that's different than a regular MRI. A regular MRI looks at the structure of the brain. So it's kind of like just pulling out a map, a paper map. It'll show you have a highway here, a road here, a loop over there. An fMRI is like pulling out your smartphone and looking at your favorite navigation app.

Dr. Bob Boland:

The F is for function.

Dr. Neil Puri:

It says you're going to get the function of the roads. It's going to show you the same map. It's going to tell you there's a slow. It can tell you there's a slowdown here, there's a speed trap there. It's telling you how those roads may be functioning.

Dr. Kerry Horrell:

That is an excellent description of the difference between MRI and fMRI. That really makes sense to me in a way that has not made sense before.

Dr. Neil Puri:

So you show up and we get an fMRI for you Okay, do we do those here.

Dr. Neil Puri:

We do them at Baylor College of Medicine. Okay, cool. So once we have that, we analyze those results using computers that take a long time to run the algorithms to analyze those results. And what we know from the evidence is that particular parts of our frontal lobe and how they're connected so we're talking about circuits to deeper structures in our brain impact the response to TMS and with the fMRI we can find the best individualized spot for a particular patient. That is a part of that circuit and it's just going to be the best spot to target. So from the fMRI we get a target. Once we have that target established, we then tune the TMS machine to the patient. Each patient is going to have a different tuning, based both on some of their scan results as well as just their physiology, which could be influenced by just who they are, the thickness of their scalp, how much calcium is in their scalp, what medications there are. So we do that and then we start the treatment.

Dr. Kerry Horrell:

Okay.

Dr. Neil Puri:

And so the treatment is going to be 50 hours. You start on Monday morning, you get a 10-minute treatment session and then you get a 50-minute break. Then you come back and get a 10-minute treatment session and a 50-minute break, and we're going to do that 10 times.

Dr. Bob Boland:

And he's targeting the magnet towards where you found in the ephemera Correct.

Dr. Neil Puri:

And we'll repeat that 10 times each day for five days in a row, for a total of 50 treatments.

Dr. Kerry Horrell:

During the 15-minute breaks, do they get to just chill out?

Dr. Neil Puri:

They can relax. I think you've come over to have therapy with a patient during that time, so they're with it.

Dr. Bob Boland:

They're not totally exhausted by this.

Dr. Neil Puri:

People do get tired but they're not unlike some other treatments you don't lose your faculties with TMS.

Dr. Bob Boland:

So it's not like ECT, where you're not going to be doing therapy right after Right. With ECT, you've had general anesthesia, you've had a seizure.

Dr. Neil Puri:

So you're limited With ECT. You've had general anesthesia, you've had a seizure, so you're limited With ketamine, you're inebriated, right. So with this I mean I don't suggest it, but you could do your taxes in between those 30 minutes if you really wanted to. Fair enough.

Dr. Kerry Horrell:

So they do this five days a week where they do 10. No, no, yeah, treatments a day, 10 minutes a day, and I wonder, I mean, do we have a sense of how it's going so far in regard to results?

Dr. Neil Puri:

I mean, I know we're new in this process, but yeah, so let me talk to you about, like in general, what we know from the literature, right, because?

Dr. Bob Boland:

you didn't make this up. This is stuff that's been done. People are starting to do research.

Dr. Neil Puri:

Right. So the results have been pretty outstanding in the research. Um, I'm gonna quote you a broad ranger, but this is new, so we don't have repeated consistent studies. We'll start honing in on like a more tight range. But there were emission rates. That means complete resolution of depression somewhere between 55 to 90 percent and this is not for people who are just like, hey, I have my first episode of mild depression. These are for treatment. Resistant depression people that's a really huge number when we think about other treatments can only just garner maybe five, ten percent improvement. Maybe things like ketamine or regular tms like 33 be completely resolved. So 50 to 90 is huge. It rivals ECT. So that's what the literature is showing and our numbers are showing something very similar to that. And the patients that we've had, like the remission rates, are in that 80-ish percent range. That's pretty incredible right, yeah.

Dr. Kerry Horrell:

I'm going to say it's badass.

Dr. Bob Boland:

Yeah.

Dr. Bob Boland:

I think, we get like one bad word every now and then is that right then we'll mess with it, um, but I mean still, it's really incredible and certainly, like you know I being the oldest person here I mean this is. I mean, if this holds, it's quite the breakthrough, right, I mean we've been kind of um since the introduction of antidepressants. The rates you're getting have been about the same, no matter what new people do. There might be new drugs coming out, there might be new tech seats apart from ect, fair enough, you know which is. You know, not everyone is going to do or is able to do. I mean it's amazing. I mean really, it's an incredible breakthrough, or could be. I agree with you.

Dr. Neil Puri:

This is an incredible breakthrough again coming back to what we were talking about earlier to have these type of results in five days. All of our other more advanced treatments, like ketamine or ECT, still take weeks to really have results that are this outstanding. So in five days, that's amazing.

Dr. Bob Boland:

Yeah, and so medication takes weeks. That's how we've always taught. Is that no matter what you do it? Yeah, and so medication takes weeks. That's how we've always taught. Is that no matter?

Dr. Kerry Horrell:

what you do, it takes a certain amount of time and a certain percentage will get better. Are there and maybe we don't know this yet, but are there major side effects that we're running into? Because it seems like, just based on, again, my limited experience of watching my patients go through it, because I have patients at any given time who are doing ECT, who are doing ketamine, who are doing TMS I've only had a few who have done the rapid TMS but it seems like, just based again on my anecdotal experience, there's just less side effects with this one compared to the other ones.

Dr. Neil Puri:

Yeah. So, as we talked about, you could probably do your taxes during your downtime Not that I would suggest it. So the major side effects are going to be it's not always going to be the most comfortable procedure. You could get some irritation on your scalp, a headache, so the headache is going to be the most common side effect. The next common side effect we see is people get tired. Now, granted, we're asking them to come really early, like 6.30 or 6.35, and then you're doing this for 10 hours and there's a good amount of downtime. So that's going to make people tired, especially if you're not used to getting up that early.

Dr. Kerry Horrell:

At the same time, they seem to be more tired than typically we would expect, so they find themselves to get lethargic from the treatment but that I mean, but all of those are going to be like at the time the treatment's happening, not something that's going to continue on that's right.

Dr. Neil Puri:

So these are just during the day, and by the end of the week these head pictures are usually less for people, maybe not necessarily the lethargy of any discomfort. They're used to the treatment we've tried to maximize things to decrease their discomfort and the side effects go away after you're done with the treatment like any long-term side effects that we've begun to see no that's wild because that feels like, especially compared to other treatments, like ecc does have not a ton, but like some possibility of long-term side effects let's hope it's going to linger for a while.

Dr. Neil Puri:

Yeah, um, but not that. We know that will continue yeah, well, it's good.

Dr. Bob Boland:

And how long does it stay like if a person gets better, how long do they stay better?

Dr. Neil Puri:

so this is new, so this is like a really burning question, like what is the?

Dr. Neil Puri:

durability for that. Right now the studies are going up for a month. What we see there is it's pretty durable for a month. Interestingly, not everybody gets their peak benefit right on the end of the fifth day. Some people will get their benefit a week or two later. We know that there's a good amount of durability that first month, but what happens after, after that, still needs to be researched and detailed. We know a lot of people do continue to do well. Some people do need to come back and either get booster treatments. There have been people that come back and got like the full course and continue to do well after that are there people who wouldn't be a good fit for this?

Dr. Neil Puri:

yeah. So, like with any medical treatment, there are individuals that we should not pursue this for, right. So this is a treatment that right now is for depression, okay, things that make someone not a good fit for this. So any type of implanted metal, not necessarily dental metal, implanted metal from like the armpit level on up, so that could be especially things like pacemakers, defibrillators, various types of brain stimulating devices whether it's a vagal nerve stimulator, we would have to talk with a manufacturer about that Any type of metal implants in the brain, maybe even if it's like a shunt, and we'd have to take particular caution with people with seizure disorders, right, because again, we are stimulating the neurons, so that'd be something that could give us like a strong moment of pause or maybe, hey look, we can't pursue this treatment for you.

Dr. Bob Boland:

I just want to ask. You know the typical skeptic questions Like, for instance, you know there's other people who have used neural imaging before, and Like, for instance, you know there's other people who have used neuroimaging before, and I think of it more of a pseudoscience way, doing spec scans on people and saying, aha, this is what's wrong, and stuff like that. I mean, how convinced are you that the fMRI matters versus just doing lots of TMS?

Dr. Neil Puri:

So first of all, looking at studies of figuring out who is going to have effective TMS. The targets that we're looking have been repeatedly shown across a variety of studies that this is the people who are targeting this tms will work. So that is one. And then also looking at more like basic or translational science studies. Yeah, we show that when we target this, like looking at studies where you're doing tms inside an mri machine some of our researchers here do for other disorders, like addictions um then this circuit that we're targeting matters. Okay, these targets have been studied in clinical trials, right? So it's not just hey, look, we have a scan, this is what's wrong with your brain. Like there is discussion about like this has actually been studied and shown to have clinical effect. So there's like the proof in the pudding there. Like, hey, we bought this, we did this scan, we thought it worked, and then we actually did a study and other people did studies and we did notice benefit.

Dr. Bob Boland:

So if you took away the fMRI and just did the rest of it with your best guess of where to put it?

Dr. Neil Puri:

So a couple of thoughts on that One, what we know with regular TMS, when it's just targeted more randomly, a lot of times you don't miss the spot, you will not get the spot, you will miss the spot, and that type of TMS is less effective. Now, in terms of studies, like I'm always interested in, where do the trials show? Where do the studies show? There are a few abstracts and smaller studies looking at doing 50 treatments in five days without an ephemera. These are smaller studies, they're just kind of abstracts that are published and those people do not see those remission results. They do see people getting better, but partially better. They don't see that full resolution of depression, full resolution of depression. There have been other larger studies that are peer-reviewed, from big TMS research groups where maybe they don't do the fMRI and they do a lower density of treatments Because 50 hours is tough.

Dr. Neil Puri:

It's a lot right, it's hard on me.

Dr. Bob Boland:

Yeah, people would say like you know, do you really need that many Right?

Dr. Neil Puri:

And again, we don't notice. What we really notice is they have the same response as regular TMS. So there's still a good thing that they did that study, because regular TMS is once a day, you know five days a week for six weeks, and so it's great that you get the same benefits. Regular TMS 33% chance for remission in a shorter period of time. That's good news for patients. We want to treat depression quicker but it doesn't get that 50% to 90% level that doing it with the fMRI and the high density that we're difficult at.

Dr. Bob Boland:

Gotcha yeah, fair enough.

Dr. Kerry Horrell:

I have one other skeptical question, which again just curious where your mind goes with this. But we measure people's depression subjectively, because that's the only way we really can measure it, right.

Dr. Neil Puri:

Yeah, so like we're measuring it with their self-report so we like to in our we do like to use a variety of validated scales, right, so we try to use a couple of self-report and a couple of objective scales to define and then the studies. They did it. They used like seven, eight, ten scales, yeah, but at the end of the day I think your point's taken care like these are. Still, I think I see where you might be going to this like subjective skills as opposed, but they are validated.

Dr. Neil Puri:

Oh, absolutely, and this is what we use in our field.

Dr. Kerry Horrell:

This is like the way to measure. But I guess because I so I um in the past have done some research on with our outcomes data around gender differences, I'm just I'm always thinking through just other reasons why things might happen. Like I was like where my mind went again. I'm just being transparent about my just a thought I had, which was if I gave 50 hours or if I did this for 50 hours, now I guess I I might just be thinking, well, I'm gonna start saying I'm feeling better too, just because, like the sunk cost fallacy, like just the idea of I've given my time to this, or you know, I should be feeling better. And yeah, I think it is one of the just tough things about depression in general, amongst other psychiatric illnesses like we just don't.

Dr. Kerry Horrell:

There's no, there's not a great way to just look at it and know you're feeling better. We have to ask them are you feeling better?

Dr. Bob Boland:

and hopefully, hopefully a randomized study, but kind of control for some of them.

Dr. Neil Puri:

Yeah, so we do have shame controlled and the shame group did not have, even though they spent the same time with the same researchers and caring team and 50 hours with this, you know whole idea of like oh my gosh, I'm doing 50 hours my life and taking a 50-hour break from my life. The people who got the sham TMS.

Dr. Kerry Horrell:

I always forget randomized control. This is why we do it. That's why we do it, because all the results there were just not much benefit. Come on science. This is where science really shows up for us.

Dr. Bob Boland:

Yeah, really. So what's next, though? I mean, you've got this that you're working on. Oh, actually, I want to back up and then say, too, that you've had good results also with suicidality, which seems awful important. Do you want to say something about that?

Dr. Neil Puri:

yeah, so there are studies out there looking at severely suicidal people with this type of protocol and they find a, you know, pretty big reduction in suicidality and this mirrors our reductions that we're observing in suicidality as well. Again, like you know, in the studies we're seeing like 65 to 95,. 90% of people have a resolution of suicidality. We're kind of in that 80% number as well. So in our cohort we're seeing similar results to what's being shown in the literature, which is good.

Dr. Bob Boland:

Well, it's incredible If it's six. Yeah, that's amazing, Absolutely.

Dr. Neil Puri:

But even if we can get people to not be suicidal for a few weeks, that could be, at the end of the day, life-saving. It gives time for someone to focus on psychosocial changes that might make a more lasting impact on their depression and suicidality, or just to get some distance from like an impulsive moment.

Dr. Kerry Horrell:

Yes, it's my ending and you can tell me if this isn't quite right, but this is my sense when I am working with patients who are doing any of the brainstem stuff. But a lot of times it opens up new possibilities in their mind for thinking that that can end up also be. I mean, that's a big part of why, like I think about this with my patients who do ketamine, you know a lot of times they'll be like I didn't feel as good after this ketamine session when I did the first one, so it might not be working, and I will often say something like well, my sense is that, like it's, over time, a cumulative effect that's also helping you think differently or open more possibilities for thinking differently, that's going to really help you in the long run absolutely, yeah.

Dr. Neil Puri:

Um, even though I do this as my daily job, I mean, I'm I'm a big believer in therapy I used to really enjoy being, uh, more of a therapist, and you know, we know this. I mean therapy is what's going to lead to lasting changes, right, and we also know that if you're severely depressed, it's going to be really hard as optimistic and as bubbly as you are, dr Harrell to fully engage and reap the benefits of your therapy.

Dr. Neil Puri:

So if we can get people feeling better, then we can do the really important work of the therapy and making changes in lifestyle that can kind of continue to sustain you and keep your depression in a lower state or full remission for longer.

Dr. Kerry Horrell:

I don't know if this necessarily is always just depression, but I've noticed that a lot with my patients who and sometimes they're depressed, sometimes they're really anxious looks all sorts of ways. Is there patients who are just so rigid, like they're so stuck in a way of thinking, like they're so stuck in their head and they cannot get out of some very rigid thought patterns that some of these interventions just like again it? I don't know, I can't, even though you just told us I can't quite feel like I grasped the science of it, but I can feel in the bedroom with them Like there's new possibilities in their mind that they're open to, where all of a sudden they can say things like I could imagine.

Dr. Neil Puri:

That looked different for me, where before they were like I just cannot at all and I think that's just been like magic to watch like people be able to think a little bit more and as we're going to learn more from neuroimaging, we hopefully will see more repeatedly, consistently, that hey look, these treatments are actually changing the resting state of the brain. The circuits are a little bit now different.

Dr. Bob Boland:

So I guess the question of what's next or where do you see this going?

Dr. Neil Puri:

So the question of what's next, or where do you see this going? So I think it's really exciting that now functional mri is being used in a proven clinical way in psychiatry and I think this is a part of where things are going next, as medicine in general, including psychiatry, is moving more towards precision medicine. So what is unique to this individual person versus the next individual person? So, um, doing more of that, get to the right treatment, the right target in the brain sooner and then, I think, also hopefully I think one of your questions earlier was kind of getting at the subject subjectivity of improvement.

Dr. Neil Puri:

Yeah, I mean, to this day we really still don't have like that blood pressure test. Okay, is your blood pressure after this intervention lower the same, or did it go in the wrong direction? Right, you'll say, hey, is your? Is there a more objective biological indication that your depression is lower and that you're going to have a better outcome? We might find that in imaging. My suspicion is it's probably a multimodal set of inputs that will lead towards score of some sort. So I think this is kind of like part of what's next in our field, in addition to other exciting things that research groups from all around the world are doing.

Dr. Bob Boland:

Hopefully it'll scale up too right, Because not too many places are doing this right now.

Dr. Neil Puri:

That's right. Yeah, so the results in these early days are very exciting. Hopefully there'll be more and more places that can offer this.

Dr. Kerry Horrell:

Yeah, I think it's all three of us are. We know what it's like to sit with somebody who has had that they're treatment resistant, like things are not working out for them, and to know that there's hope on the horizon for ongoing possibilities for them to get better. I think it's huge. I mean, as a provider, that brings me a lot of comfort, because it's really painful to sit with people who have tried and things aren't working and they're really depressed.

Dr. Kerry Horrell:

Yeah, like it's really sad and it's heartbreaking, and so I'm so grateful for the work you're doing. Thank, you. So thank you. Any last word for our guests today. Dr Bray, these are mental health clinicians.

Dr. Neil Puri:

I don't know if we really said that, but yeah. So for our mental health clinicians, I really want just to remind them that, as they're working with people who have been struggling long and mightily with depression, just that there are other interventions out there, yeah, and that there is hope on the horizon, a lot of these, and it may not be necessarily this treatment, but there's a variety of treatments in addition to just the meds and therapy that may provide them with relief.

Dr. Kerry Horrell:

Well, it's great to see and we're really grateful for your work. Dr Pree, Thanks for coming on the podcast.

Dr. Neil Puri:

Thank you.

Dr. Kerry Horrell:

You've been listening to the Mind Dive podcast. I'm one of your hosts. I'm Dr Keri Harrell.

Dr. Bob Boland:

I'm Dr Bob Bowen. Thanks for diving in.

Dr. Kerry Horrell:

The Mind Dive podcast is presented by the Menninger Clinic. If you're curious about the professional experiences of mental health clinicians, make sure to subscribe wherever you listen.

Dr. Bob Boland:

For more episodes like this, visit wwwmenningerclinicorg.

Dr. Kerry Horrell:

To submit a topic for discussion. Send us an email at podcast at menningeredu.