The Mental Health Forecast explores cutting-edge developments shaping the future of mental healthcare. Each episode features conversations with researchers and innovators about emerging therapies, technologies, and approaches to emotional wellbeing. From AI-powered therapy tools to advances in neuroscience, we examine how these changes might transform mental health treatment. Join us as we investigate what's on the horizon and discover how tomorrow's solutions could help address today's mental health challenges.
Arjun Nanda (00:01.079)
All right, everybody. Welcome back to the podcast. I have the immense pleasure of meeting with Owen Scott Muir, MD. He is a child and adolescent psychiatrist and a distinguished fellow of the American Academy of Child and Adolescent Psychiatry. And his mother is very proud of him. So thank you very much for being on the podcast and I appreciate your time.
Owen Muir, M.D. (00:31.246)
My mom, Vita Muir, is a medical editor, or those are first line of work. And I still actually will have her sometimes copy edit some of the manuscripts I'm writing if they need to be any good. So.
Arjun Nanda (00:36.791)
huh.
Arjun Nanda (00:43.767)
This is genius. See, this is the power of having a strong mom or dad in your life. They can do all this stuff for us and they're always holding us accountable.
Owen Muir, M.D. (00:58.35)
She was the editor of the biomedical reports of the Apollo space program. So like, she's just better at that than I'm ever going to be. And she didn't end up going on to become a physician. I did, but it doesn't mean I can copy at it. So.
Arjun Nanda (01:05.559)
Ha ha.
Arjun Nanda (01:12.535)
Right, right. See, she's got a certain skill set that works.
Owen Muir, M.D. (01:19.15)
Yeah. So a pleasure to join you. What are the, you know, it's a big world out there, but what's coming in hot today for you?
Arjun Nanda (01:30.071)
Yeah, I mean, I think that I've been following your work for a while. I've been watching all the stuff that you've been doing with regards to TMS, you know, Ocasio Clinics, you know, the stuff that you're doing at Fermata. And I'm really a fan of pushing the frontier of psychiatry. And I think that's also perhaps the inspiration for your Substack. So I just wanted to get to know a little bit about...
the work that you're doing, you know, with regards to pushing psychiatry forward. yeah.
Owen Muir, M.D. (02:03.79)
Yeah. So the future is really bright. And I'm kind of surprised to hear myself say that because it's been hard. Things have been getting worse for most people, or many people at least, and especially young people. And so all child psychiatrists are also general psychiatrists, or the vast majority of us are.
And so I started my career thinking, well, this is great. I'm gonna go to medical school and I'm gonna learn how to prescribe pills and those are really gonna help people. And I got to psychiatry residency and they weren't as good as I thought they would be. And I learned, started learning psychotherapy as a modality, which I consider a higher level intervention than regular care, but still with kind of the mindset of a physician. So I'm thinking about.
the combination of biology, psychology, and social circumstances or biopsychosocial model of medicine, which was baked into me from the University of Rochester, where I did medical school. And so I'm like, what's going to help? And so it turns out talking in certain ways, like mentalization -based treatment or MBT from the Antiphroid Center in the UK is very useful in people who haven't responded to other things. But it sure seemed like there were a lot of people who didn't respond to other things. And
And one of the things I had kind of pish -poshed was a modality called transcranial magnetic stimulation, or TMS, which was the coil was invented by Ted Barker in the UK. And the treatment version of that for depression was developed by a doctor named Mark George at the Medical University of South Carolina. And I'd seen the data and I was underwhelmed. And then I got depressed.
Arjun Nanda (03:46.119)
It happens.
Owen Muir, M.D. (03:47.822)
And I have bipolar disorder. I've had it since I was a young person and I was in my fourth year of residency and I've been seeing my psychiatrist forever. And he said, look, go see this guy uptown. He's kind of kooky, but you'll probably like him. And look, if it works, it's easy to recreate. I said, but the data, he's like, yeah, but look, if it, the downside of finding out it works is really low.
Like, okay, whatever, I just do whatever you say, Mike. And so I did it. And after my first treatment with transcranial magnetic stimulation to my left front of my brain, I was hungry. Like I ate a full meal and I went, what's this witchcraft? My wife who's also a psychiatrist, Carlene McMillan, she works at Osmine and is actually on the board of directors of the Clinical TMS Society now.
Arjun Nanda (04:19.863)
Right. Right.
Owen Muir, M.D. (04:47.278)
in addition to other gigs she has, which is a lot, like National Quality Foundation and the American Psychiatric Association, blah, blah, blah. She's a heavy hitter compared to me. And she saw me after I got TMSO over the weekend that first week, and she saw me kind of walk in looking like a zombie and walk out looking like a normal person. And both of us were like, this is different than what we've learned to expect as psychiatrists from treatment for depression. And that led me down the rabbit hole.
Arjun Nanda (04:57.047)
Mm -hmm.
Arjun Nanda (05:12.247)
Yes.
Owen Muir, M.D. (05:14.862)
And so I eventually started my own practice at the end of, I was actually day one of fellowship, July 1st. So I finished my TMS treatment in April of that year and I was starting a private practice a couple months later and ended up getting my own TMS machine before I graduated fellowship. In residency and fellowship training, we have these things called the milestones where your program directors are supposed to sit down with you and review your progress across different.
Arjun Nanda (05:22.807)
Hmm.
Arjun Nanda (05:27.199)
Hmm. That's incredible.
Owen Muir, M.D. (05:44.59)
Modalities and I hadn't made a big deal about having my own TMS practice I mean I was allowed to do it but like I kind of didn't want to hear about it from my bosses at day job, you know, so there they didn't know and On my milestones review like six months before graduating, but we think you're a little behind where you should be in your second year of Fellowship training on understanding somatic modalities and I went hmm. I'll work on that
Arjun Nanda (05:45.463)
Right.
Arjun Nanda (05:54.903)
Yeah. Yep.
Arjun Nanda (06:10.167)
Hahaha
Owen Muir, M.D. (06:13.934)
And now I'm a published author on every large post -marketing data set that exists on transcranial magnetic stimulation that is either neuro -navigated or with deep TMS. And those are different in ways I can talk about. But I did have to work on it. They weren't wrong. Yeah, I was on my own time. There's so much for us to learn. And there are, what I learned from that is kind of, I think, more broadly applicable. It's not just one mode out.
Arjun Nanda (06:29.619)
Just on your own time.
Owen Muir, M.D. (06:42.638)
It's that remission of depression is possible. And psychiatric illness doesn't have to be 50 % better as the only possible outcome. It can be over. Which by the way, doesn't mean your life will be great. You may have other problems that are very challenging. You may have other psychiatric problems that are still there or uncovered. You may have an autoimmune disorder or your whole life may be built on the plan that you're gonna get depressed again and that doesn't fit anymore. And now, my gosh, what are you gonna do?
So it's very humbling to see depression be over and repeatedly, like in hundreds and hundreds of cases. So it's not like the panacea is less panaceae than you'd imagine, like curing something, at least for the time being, which is a word we don't usually use. I think it's accurate in this case if you look at the definition, like the definition of the word cure is to remove all signs or symptoms of a disease.
And in psychiatry, at least when our interactions with the FDA have taught us, don't say that word. So I can buy powder for my feet that says it will cure athlete's foot, even if we all know athlete's foot could come back. But there's no depression treatment, even if it got it to remission, that I can say the word cure. And so I don't, because I'm an adult. And even a cure of athlete's foot doesn't mean you don't have a foot problem, right? You could have...
plantar fasciitis or something. I look forward to more interesting problems. That's kind of like my little introduction. Is that enough? OK.
Arjun Nanda (08:20.567)
Yeah. Yeah. I mean, this is, it gives us plenty to, to work with. I mean, there's, I think a lot of us in, in psychiatry, especially child and adolescent psychiatry have a lot of frustration with the way that things currently are, you know? I mean, even in adult psychiatry, the medications, the effectiveness is not as ideal. And then with children, there's a lot more side effects and a lot more problems that come with it. I mean, maybe.
Owen Muir, M.D. (08:49.806)
I think for a minute, for general audiences, the things we do in psychiatry work. How much of that is just because we care and that's effective is what we're arguing about. So if you go cake your kid to a psychiatrist, the chances are they're going to feel better. It doesn't actually matter so much what we do.
Arjun Nanda (08:59.479)
Yeah. Right.
Arjun Nanda (09:08.567)
Yeah. The therapeutic relationship is half, if not more than half the battle.
Owen Muir, M.D. (09:14.574)
And of course it is because we evolved to have those connections with other people be the things that got us through. So that's obviously a thing that makes sense to be powerful. So the hope is there, the hope for people for whom that's not enough, that's what I'm really interested in. And yeah, yeah.
Arjun Nanda (09:31.703)
Right. Can we talk a little bit about the efficacy here? You mentioned there's a few different types of interventions within TMS. Can we get a little bit deeper into that?
Owen Muir, M.D. (09:42.767)
Yeah. So this treatment started being delivered five times a day, once a day, using a frequency that seemed to work at first. And I know that because I know Mark George, who invented it. And so he went to the UK and met the person who developed the coil that was making the arm move when you put it in the motor cortex and said, why don't we put it here? And got pushed back for years. Eventually he did the first trial, which turned into the first kind of pivotal trial. And it was effective in treatment resistant depression.
And by effective, I mean the best data on that sort of TMS, which is with a figure of eight coil, is we're getting to remission about 30 % of the time, which is not nothing in treatment resistant depression. In depression that's failed the medication, the remission rate is less than 10 % for most people. So it's three times as good as a pill. Now,
What happened was if you look carefully at those trials over the years, we did more and more and more of them. And this is a low risk intervention. So it's relatively safe to use in novel ways for people who haven't responded and also ethical. It's unlikely to hurt someone, causes no permanent changes in brain functioning, and has limited side effects. Very rare incidence of seizure between one and 30 and 150 ,000. Like it's rare, rare, rare. I've seen it. Uncommon. Even the seizure is induced, so it's not epilepsy.
Arjun Nanda (11:01.367)
Mm -hmm.
Owen Muir, M.D. (11:06.19)
Tinnitus is an extremely rare side effect, but there's things that can go wrong. What we found was that we got the dosage wrong. And we got the pattern. The first pattern we picked wasn't the best. Shocker, right? And the 45 minutes you can hold up the coil before there's an arm for it might not be the best interval. And 24 hours between treatments, well, maybe that's not the ideal interval either. And so Dr. Nolan Williams at Stanford took a look at the data and said, well,
Arjun Nanda (11:18.519)
Right.
Arjun Nanda (11:23.487)
Yeah.
Owen Muir, M.D. (11:35.406)
I was actually a neurologist first, not me, him, but he was at MUSC and he was doing neurology and switched to do psychiatry and then behavioral psychiatry fellowship. And in deep brain stimulation for Parkinson's, we were using 50 ,000 pulses a day. And in TMS, we were using 2 ,000. He said this didn't make sense. And so increasing the doses was part of that picture. And the next question is like, well, where do you point it? Well, a couple centimeters forward.
from where your thumb moves is good enough, but is it the best? And it turns out the best answer is using functional magnetic resonance imaging, or fMRI, and using functional connectivity between different regions of the brain. So he developed a protocol, which is a trademark product of Magnus Medical, which is a company he had to spin up because no one else would do it. And Magnus now has this as a commercial product.
Arjun Nanda (12:15.383)
Right.
Arjun Nanda (12:27.159)
Hmph.
Owen Muir, M.D. (12:31.31)
It's available at a couple of sites in the US, and I hope to do one of those soon. Acacia Clinics is the first. We have MUSC has deployed this treatment. University of Arkansas and their medical center has some inpatients, some outpatients. And we're taking a brain scan. And it's just like if you're assessing what's wrong with the golf swing, you don't x -ray the club only. Like you could x -ray the club. Maybe it has a bend and you need a new club. But usually it's the actual swing that's the problem.
Arjun Nanda (12:45.495)
Mm -hmm.
Arjun Nanda (12:53.047)
Mm -hmm. Right.
Hmm.
Arjun Nanda (13:01.303)
yeah.
Owen Muir, M.D. (13:01.614)
And it's a motion problem in our brain. And so that motion problem overlaid over the structural image is how we get the right target for the stimulator. And then we're doing it 10 times a day, spaced out by 50 minutes. So the best time between that new pattern, which is called intermittent theta burst, and that's because it's 50 Hertz at a five Hertz burst frequency. And that's interesting if you like, you know, brain science, but not that it's faster. That's what matters. It's it's not 45 minutes. It's.
Arjun Nanda (13:28.919)
Sure.
Owen Muir, M.D. (13:31.726)
eight, nine. And you do that 10 times a day spaced out by an hour, which is the same interval for learning that you use with flashcards, right? 60 in a deck, one an hour. Hey, you learned a thing. And you learn it more efficiently than looking at it at noon every day, and that's it. And so that's what ended up working. And the remission rate in randomized controlled trials of that is 79%. Yeah, depression is over.
Arjun Nanda (13:32.599)
Mm -hmm.
Arjun Nanda (13:44.823)
Right.
Arjun Nanda (13:57.335)
Wow.
Owen Muir, M.D. (14:00.078)
Now, that seems really good, and you're going to say, well, it's probably not that good out of studies. And yeah, you're right. So in real world samples, it's well over 65%.
Arjun Nanda (14:09.911)
That's a high translation, right? To, yeah.
Owen Muir, M.D. (14:11.438)
it's an extremely high translation rate. And I think it probably accounts for the fact that some of the individuals in those non -study cohorts have things that were ruled out of the study. So I think in pure depression that doesn't co -occur with obsession, 79 % is a real number. And when we have co -occurring OCD, Obsessive Compulsive Personality Disorder, or other problems, trauma, for example, maybe other targets will end up being more effective. But it's a rapidly effective treatment for depression and suicidality.
Arjun Nanda (14:20.247)
Right.
Owen Muir, M.D. (14:41.838)
anxiety tends to get better. There are other targets we use as well. Edekesha is using Sean Siddiqui's anxiety somatic target on the right. And again, this is just the first of the neuromodulatory treatments to come to market. In my practice, I also deploy the PRISM system EEG neurofeedback for PTSD. And that it looks like we can also accelerate the speed of deployment of or using the Monarch transcutaneous
Trigeminal nerve stimulator, which you sleep with on your forehead. I actually use that myself because I have ADHD and that's approved in kids. Twice as effective as stimulants in half of children. And GammaCore vagal nerve stimulation held to your neck non -invasively. It's just two minutes at a time stimulating your vagus nerve approved for migraine, hemicrania, continua, and cluster headache. And going through the FDA breakthrough process for post -traumatic stress disorder.
Arjun Nanda (15:14.839)
Mm -hmm.
Arjun Nanda (15:18.583)
Wow.
Owen Muir, M.D. (15:37.39)
It's and that's you know, we have T fuss coming to market transcranial focused ultrasound like wow, there are so many ways to change your brain that are an appeal you take once a day.
Arjun Nanda (15:43.191)
Right.
Yeah, incredible.
Owen Muir, M.D. (15:48.078)
Yeah.
Arjun Nanda (15:49.655)
There's so much on the horizon. What of these are all neat interventions that you need to do in a clinic or an outpatient setting? Is there any way that you can do this stuff at home or any of these?
Owen Muir, M.D. (16:02.382)
So Monarch and GammaCore are examples of at -home treatments. And so the Monarch, you're prescribed by a doctor, but you place it on your head or your kid's head at night. And that's on you. I mean, my wife's a doctor, so I guess it's in a doctor's office. But I'm kidding. The GammaCore device you take home, Saint is done in an office, and it's after you get an fMRI.
Arjun Nanda (16:13.867)
Mm -hmm. Mm -hmm.
Arjun Nanda (16:20.023)
Ha ha ha ha.
Owen Muir, M.D. (16:28.11)
And, you know, deep TMS, similarly made by the brain sway company, which targets larger areas of brain. And we have some cases where people have gotten st and haven't remitted and then gotten deep TMS and have, I just published a whole case series with my colleague Irfan Handu in Kansas city, where we looked at people who had gotten ECT and ketamine and TMS. None of it had worked. We gave them deep TMS and they're in remission. So which stimulator is going to matter for different people? And we just got to figure that out.
It's a remarkable new frontier of people who had no hope suddenly having a hopeful life be an option. And that's, again, like...
Wow.
Arjun Nanda (17:12.023)
Yeah, it's a big deal for this population. I mean, like you said, treatment resistant depression, our interventions thus far have not really worked. And that's what makes it treatment resistant. I mean, that's the definition of it.
Owen Muir, M.D. (17:23.182)
Yeah. Yeah. Well, I mean, I think we defined it based on something that was like, we define a lot less things as treatment resistant depression if we started with SAIT. But I actually don't know how, I mean, there may be like SAIT resistant depression that only responds to Prozac. Right? We just don't do it in that order. Because it doesn't make sense for a study. It doesn't mean it's necessarily the rational way to go about it.
Arjun Nanda (17:41.843)
Yeah.
Arjun Nanda (17:49.335)
Sure. So that leads to the question, where in the hierarchy would you like to see things for TMS? Could this be a first line, second line, or what are you thinking?
Owen Muir, M.D. (18:00.494)
So my very strong feeling is that transcranial magnetic stimulation could be moved to the first line of treatment. There are economic reasons why that would be challenging to change our current models, but that's a model problem, not a medical problem. At the end of the day, when I look at the data, the chances are that your depression is going to be over if I give you CMS. And that's less likely to be true if I give you a pill.
And the side effects are likely to be worse if I give you a pill and more dangerous if I give you a pill and lead to other pills and weight gain and metabolic syndrome and tardive dyskinesia if it's an antipsychotic. Those are less safe interventions that are less effective. And transcranial magnetic stimulation is faster acting depending on how we do it and more robust and safer. It's also more effective. Now we've only studied that meaningfully.
Arjun Nanda (18:45.587)
Mm -hmm.
Owen Muir, M.D. (18:56.91)
in people who've already gotten an oral medication because we just anchored on that concept that you give oral medication first. But were anyone to want to study treatment of first episode depression with TMS, I don't think it would do worse.
Arjun Nanda (19:13.399)
Right. Yeah.
Owen Muir, M.D. (19:14.062)
I could be wrong. It's harder to study because there's more placebo response in that population. But that's a study problem, not a... I mean, if you're asking me for like a family member, what would I recommend? TMS in a heartbeat. Like, what are you, serious? Do the thing that's gonna work like more than half the time and not eight weeks late. Like, just the fact that it works fast is good enough. Like it doesn't even have to be better. It just has to be faster. How long do you want to suffer? Five days or months?
Arjun Nanda (19:29.143)
Yeah. Yeah.
Arjun Nanda (19:38.999)
Right.
Owen Muir, M.D. (19:45.166)
But yeah, there's, yeah, I don't write all the rules. I certainly don't write all the insurance policies. I don't price devices or train doctors all day long. So it's not up to me, but it sure seems strange that we use more harmful, less effective things first.
Arjun Nanda (20:00.215)
Mm -hmm.
Arjun Nanda (20:04.487)
Right. So the question that I have here is then what does maintenance look like? Once a day pills, you can take that for a while and not much cost to that beyond insurance, but what does it look like for TMS?
Owen Muir, M.D. (20:21.07)
So first off, I think the assumed cost of TMS is higher than it probably needs to be. Like, if you just look at the cost of building a device and putting it everywhere, like, you can build a TMS device for $25 ,000 if you build devices for a living. Right? You can buy one off the shelf for between, you know, $50 ,000 and $250 ,000 depending on the device. We prescribe medicine all the time.
that comes in a injectable. And I know, cause I take this, like I take Skyrizzy for my autoimmune disorder. That's $20 ,000 a dose. So every, and they ship it to my house, right? So every day people are getting medicines that cost more than an entire TMS machine at your house forever. And like it's like, co -centics is $250 ,000 a year. We could get every person with depression.
their own TMS machine in their living room if we really paid for it like we paid for Cosentix. But there's no kickback on buying someone a TMS machine to the pharmacy benefit manager. But again, the average cost of a new drug coming to market in 2023 is, sorry, 2024, is $300 ,000 a year. So just calibrating our expectations about what a cost is and what a cost could be, I think it's important in the overall, the cost of depression.
makes any general medical expense 44 % worse? And that's data from the Validation Institute, which is cost effectiveness research in healthcare. And so the actual answer is it's more expensive to not give very sick people TMS. And at least right now, it's probably more expensive to give people TMS first line, but the eventual cost of ineffective treatment is much higher. And so for people who are not the 30 % of people who get better with the first drug and then may have significant side effects by the way,
they're gonna need something better. And a recent trial called the Astrotane TRD study demonstrated that TMS was better than either switching drugs or augmenting with aripiprazole. And so it is in randomized controlled trials, the best next thing. And so I think the best answer right now is this is hands down the best second line intervention. It should be like try drug or therapy and next thing is TMS. But I hope we move to first line TMS and driving down the marginal cost and accessibility of that treatment.
Owen Muir, M.D. (22:45.613)
is crucial for that process. Or it might be something else. Like we may develop an ultrasound device that just goes on your head at home, and then you don't have to go anywhere. And it's cheaper, and it's $300. I don't know. The future's coming.
Arjun Nanda (22:47.255)
Right. Now.
Arjun Nanda (22:58.487)
Yeah, or implant something like Neuralink or using that sort of techniques.
Owen Muir, M.D. (23:02.318)
Yeah. And so, you know, Dr. Williams has worked on stuff like that in past in Parkinson's, and I don't doubt it's part of the future. And those are for more severe cases. I think the kind of maintenance approach is going to be like, well, we already have this figured out with dialysis, right? You get it more because you die if you don't get it. And you don't necessarily immediately die with depression, but you do die 25 years earlier for severe mental illness. And that's not okay either.
All that being said, innovation is coming and we have to get our payment models out of the way or aligned with actual value and not just value to pharmacy benefit managers, which make, I mean, the amount of money made by pharmacy benefit managers every year, and those are the people who reprice drugs and are overwhelmingly wholly owned subsidiaries of insurance companies, is $485 billion a year with an 8 .8 % combined annual growth rate. And that is the equivalent.
of the 2024 adjusted cost of the entire Apollo space program, plus the entire space shuttle program, plus 10 times the Hubble space telescope, and we're still only at 2012 levels. So you can go from here to Saturn for a dollar a meter for less than the cost of repricing drugs into tiers, not making drugs, not dispensing drugs, not the doctors, none of it just.
Arjun Nanda (24:17.367)
That's absurd.
Owen Muir, M.D. (24:29.71)
how much extra kickback should move around from the prescribing of a drug from here to Saturn for a dollar a meter every year. And if we wait, we'll get to Uranus.
Arjun Nanda (24:43.031)
happen. The issue here is that ultimately this falls back on patients and more suffering for patients, dealing with less access to care, to worse treatments, ineffective treatments, that eventually it ultimately kills patients.
Owen Muir, M.D. (24:59.054)
And the bottom line is you gotta look in the mirror and say, is what I'm doing actually effective? And if your answer is not a clear and unambiguous yes, what the hell are you doing?
Arjun Nanda (25:09.043)
Yeah, that's a problem.
Owen Muir, M.D. (25:10.766)
And so that's why I stopped. I stopped thinking of these things as second line treatments. Now practically most people who come to me are not coming out of the blue because they have no problems and haven't tried anything. It's new. So they haven't heard about it at the beginning. They've heard about therapy, whatever that is, from whoever they saw, or they've heard about pills. And if they got better already, they don't have to see me. Every once in a while, someone's lucky enough to have a family member who says, try this first, and they do.
Arjun Nanda (25:13.015)
Mm -hmm.
Owen Muir, M.D. (25:37.902)
And that's a luckier state of affairs, but often it's years of suffering, which I'd like to see less of.
Arjun Nanda (25:43.094)
Right, right. So, you know, as a first line treatment, if it were to get to that point, is the main barrier that you see the financial structures in place that de -incentivize that, or is there anything else that you're seeing that could push it up to as a first line treatment?
Owen Muir, M.D. (26:04.334)
Well, I mean, we have to have the evidence to support that first. And we don't. I see plausible reasons to run that trial. But I don't have the evidence to say it's a better first -line treatment. It may be that people with treatment -resistant depression have whatever a different depression is. And when I give it to all people with depression, it does not perform that well. And my guess is it's unlikely to harm them. But I don't know. I literally don't know if those are different.
biological conditions that respond differently. I just, I don't know. It may be completely inappropriate. It may be more harmful to people. Like I just, I can't know because we've never used it in those populations. I'm dubious. I don't think there's any reason to suspect it'll go badly, but look, we're wrong about stuff all the time. So some humility is necessary.
Arjun Nanda (26:53.431)
Sure.
Owen Muir, M.D. (26:54.797)
And then we, if that were the case, if this were the best treatment for depression and it was safer, faster and more effective than everything else we had, then we have a serious conversation with ourselves about why we're letting depressed people suffer needlessly compared to how we treat everything else. We don't say, if you broke your leg, we can't go to surgery yet. You have to limp for six months before us to consider it unless we're, you know, I'll make a candid joke, but they probably don't do that.
Arjun Nanda (27:24.215)
Ha ha.
Owen Muir, M.D. (27:24.846)
There's some kids like you have a stroke and no one's like, well, let's try watchful waiting before TPA. You have to, let's wait for six weeks. You're gonna die if you have a heart attack, you have a stroke. We gotta do something right now. And I hope for a world where we treat depression like that and we get at least serious depression to remission rapidly as a thing that keeps people from death and suffering.
Arjun Nanda (27:34.263)
Yeah, let's wait for six weeks, you know.
Owen Muir, M.D. (27:52.174)
And maybe it goes from serious depression first to less serious depression later, and we'll see. But my hope is that we take depression just as seriously as we take other medical conditions that we are serious about.
Arjun Nanda (28:07.191)
Yeah. Yeah. Ultimately, you know, a lot of this stuff comes down to stigma. and, it's a, yeah, it's, it's a problem. I mean, patients not getting good access to effective treatments is, you know, these are the barriers that have been keeping patients in the shadows for, for so long.
Owen Muir, M.D. (28:26.542)
But it's not just stigma, because if it were stigma, it would be, I mean, almost easier to address. I think there are baked in assumptions. So the PHQ -9, the broadest screening tool, which turns out to also be validated as a rating scale for depression. When you answer those questions, it says, in the last two weeks,
Owen Muir, M.D. (28:52.526)
How about the difference between yesterday and today? It can't measure that. So we built tools based on assumptions that might not be true. And when you can get better on a time scale that's faster than two weeks, what the hell is the PHQ -9 gonna tell you? It's gonna lag. So we need tools that work faster to measure. And so that's some of the other work that I do in artificial intelligence. I'm the author of a study called, Quantifying the Effects and Process of Psychotherapy at Scale with Mind Medicine.
I was the principal investigator on that. That's capturing large -scale video, text, and medical data from interactions with doctors and therapists. Another project is with a company called Vidara Health where I'm an advisor. And we built a Tardype dyskinesia detection algorithm. And they also have an algorithm to rapidly measure depression at the equivalent of a PHQ9 score based on a couple of simple questions and video capture. I'm an advisor to a company called Siren where we look at that same question with audio and schizophrenia.
And so I think building more rapidly acting tools using observational AI approaches is going to be part of measuring more rapidly things that we assumed we couldn't measure fast enough. But if you only ever had a meter stick that never had notches on it, everything would be a meter or more or less. And so we have the same problem with depression. We didn't imagine how quickly it could resolve. And thus, we built no tools to measure it.
Arjun Nanda (30:11.191)
Mm -hmm.
Owen Muir, M.D. (30:20.366)
And that's robbed us of the ability to tell the difference.
Arjun Nanda (30:20.439)
Right.
Right. Okay. Can you speak more to the type of tools that you're using to detect changes in depression?
Owen Muir, M.D. (30:30.03)
Yeah. So in my work with Videra, who are great, they're great people to work with. I'm the chief medical officer of a company called IREX Reminder. And we build medication adherence technology and we co -developed some of that movement disorders tech with Videra. Videra did the HIPAA compliant video capture. And they also have a tool that rates depression. And so what they found was, you know, it's AI. So you feed it enough data and it can figure it out.
And so they had lots of people answering the questions on a video of the PHQ -9. And it turns out you can just ask some version of how was your day. And the answer to the question, how was your day, plus all the data about your voice and what you look like on the video, is enough to answer the question of what would your PHQ -9 have been. Similarly, our TD screen tool detects this adverse effect of eschonic medications and involuntary movement disorder called tardive dyskinesia.
And you can do the whole aims, you know, involuntary movement scale, which takes 30 minutes, or you can ask someone one question on video that's been trained on a bunch of experts like myself, rating those same individuals on the aims. And it learns that the screening tool is so close. It's actually better than any human is with the other raters. So the AI algorithm to how are you doing and looking for adverse movements is more reliable.
than two expert human raters are to each other. And we're running the final analysis on that for the submission to the FDA and the diagnostic soon, but the screener exists now. So that risk stratifies it doesn't diagnose, which is of course an important difference if we're talking about regulators. But we're enthusiastic about taking it through the regulatory processes of class two medical device in the future.
Arjun Nanda (32:01.879)
Hmm.
Arjun Nanda (32:21.975)
That's incredible. That's incredible. It's going to save a lot of time. It's going to increase efficacy.
Owen Muir, M.D. (32:28.81)
Yeah. And so part of the idea is like, well, I think movement disorders and mood disorders are the same thing functionally at the level of the brain. Like you're not moving or you're not feeling right for the same brain miscommunication reasons. And so I'm hopeful that we're going to be able to capture the movement of your mood from the things you say and the way your face moves around when you say it. And that's going to be our next set of measurement tools. That's going to be the stethoscope for.
you know, psychiatry going forward. My wife works with the American Psychiatric Association and Osmine on a tool called the DSM -5 cross -cutting measure, which is a little bit like the PHK9, except instead of just depression, we're looking at a little bit of personality dysfunction, a little bit of dissociation, a little bit of this. So we're looking at broad domains of personality dysfunction and mood and trauma and attention, et cetera. And so having ever more useful stethoscopes.
by artificial intelligence as part of that vision that will allow physicians to know with what we heal and in what order.
Arjun Nanda (33:36.055)
Right. Have you thought of, or is there a plan to use other pieces of technology like sweat detection or anything else to assist?
Owen Muir, M.D. (33:48.782)
So we've seen some data on pupilometry that's promising. EEG, I'm already using down the hall with the PRISM system. And so it turns out there's been TMS synchronized with EEG in the works for years. That turns out it's very hard to do. It's actually easier to entrain the brain with an electrical signal than it is to measure and then try to change it and sync with it because the brain is entrainable.
Arjun Nanda (33:51.607)
Mm -hmm.
Arjun Nanda (33:57.591)
Hmm.
Arjun Nanda (34:11.607)
Hmph.
Owen Muir, M.D. (34:16.782)
But we're using EEG to do some of that measurement now. Sweat detection, I don't know the data on. But there's a world full of biomarkers, heart rate variability. The more we have the data from wearables and the more we try to understand from what's observable and measure the human condition, the better we are. And so I'm very hopeful that that combined approach using all the data that we can get is going to power those AI models to be ever more discriminatory.
Arjun Nanda (34:47.415)
Right, right. The future is bright.
Owen Muir, M.D. (34:52.462)
like, yeah, and we haven't even gotten to psychedelics yet. But they're, you know, a whole class of medications that I just wrote a series of reviews on for our primary care colleagues in the American Journal of Therapeutics with co -authors, including the wonderful Burton Tabak, who I'm just such a huge fan of. He's a neurologist out in Reno. And what a thoughtful person. But you know, we're looking at things like magnesium ibogaine, also work Nolan Williams published in Nature Medicine.
for traumatic brain injury and co -occurring PTSD. And we've seen psilocybin, it's going through the process with Comp360 and psilocybin has a compound as well. Compass is the Comp360 company. We have LSD from Mind Medicine, MM120 is their version of that, which is top lining on its phase 2B trials. And they just actually finished their planning meeting with the FDA for the end of phase two. So that's, 50 % of generalized anxiety disorder in remission after a single dose.
durable at 12 weeks already, like great. But again, like which and for whom? And I think that's a measurement question that we have to meaningfully answer by stopping assuming it can't get better fast.
Arjun Nanda (35:53.271)
Yeah. Yeah.
Owen Muir, M.D. (36:03.854)
and then the payment miles have to keep up with it. It'll be easier with drugs because we already have ways to move money around. But hope is kind of the bottom line. Are these things better than anything we've ever had? Yep.
Do we have ever reason to keep working hard to determine what's good for whom? I think so.
Arjun Nanda (36:27.895)
Yeah. The tools to detect or to screen or filter out and stratify, as things improve with wearables, do you have any, what are your thoughts on wearables and detecting things like, you know.
Owen Muir, M.D. (36:47.086)
So again, as the principal investigator of the mind medicine study on their session monitoring system, which was a wearable technology, and a dear friend of Grady Hannah at Nightwear, which is also a company started by the chief science officer, Dan Carlin, who's now at Mind Medicine. But that's a wearable in an Apple Watch for PTSD -related nightmares. So like right now, we have an FDA -approved treatment that will disrupt nightmares you're having and not wake you up.
but knock you out of the nightmare by vibrating on your wrist. And like, that's some Star Trek stuff. Yeah. And so we can treat PTSD related nightmares with an effect size of 0 .88, right? Which is like almost two additional inches in height if it were a height medicine. And it's not a drug, it's an Apple watch that you wear on your wrist that's specially provisioned. So I think like if we can do that, and if we can monitor Spravato sessions for safety using a similar Apple watch based design.
Arjun Nanda (37:21.815)
That's amazing.
Arjun Nanda (37:28.695)
That's amazing.
Owen Muir, M.D. (37:45.198)
which is what we did in the SMS trial, of which I was both the designer and the principal investigator. One of them actually was Amanda Tinkleman. Like what else can we do? Like it's exciting. And there's more coming that I can't talk about yet, but I'm excited when I can. That's published. Look, there's so much of our biology to capture and I'm psyched to do that.
Arjun Nanda (38:01.271)
Hahaha
Arjun Nanda (38:09.047)
Yeah, that's excellent. One last thought with regards to this detection in the future is virtual reality, augmented reality. When that comes to scale, it's already out there with the Apple Vision Pro. Yeah.
Owen Muir, M.D. (38:33.678)
I love that thing. my God. I don't have one. I want one. I mean, I want, I, there's like, so the Apple vision pro is really good. And I think already we're seeing people with disabilities embrace that device because it does all the disability accommodation stuff so much better than anything before. You can have a, a functionally 30 foot high, you know, screen to that other people aren't staring.
Arjun Nanda (38:37.623)
Hahaha
Owen Muir, M.D. (38:59.79)
You can modify that for all sorts of impairments and disabilities. And that is just an accessibility tool par exelots. But it's also using remarkably effective eye tracking, probably pupilometry available, right? There's so much measurement that could be done in that device. So am I excited to see where that goes? Yes. Is it going to take diligent science to get us there? Also, yes. Apple, call me.
Arjun Nanda (39:24.087)
There we go. Apple, if you're...
Owen Muir, M.D. (39:25.742)
I love that. I love Apple as a company. They're adults and I find that delightful.
Arjun Nanda (39:30.647)
Yeah, that's great. Well, Apple, you heard it first over here. Call Dr. Mirror.
Owen Muir, M.D. (39:39.438)
Hey girl. What we've done without the discipline of a company like Apple is remarkable already. But I do think that there is a disciplined approach to bringing a product to market that medicine is just not good at. Like we're great at sussing out what might be a useful thing, but actually productizing it, making it useful, accessible, easy, intuitive. We suck at that. And there are great economic reasons we suck at that.
Arjun Nanda (39:55.415)
Mm -hmm.
Arjun Nanda (40:06.103)
Mm -hmm.
Owen Muir, M.D. (40:08.814)
that are not so great, but they're understandable. But we are not good like Apple is good at bringing new health products to market. When there is a new iPhone, we will sure as F hear about it. There could be a cure for depression and it may be news to people who are listening right now. Or a treatment that can get you to remission 79 % of the time because I can't call it a cure.
Arjun Nanda (40:29.047)
Right. There's an asterisk right beside that by the word cure.
Owen Muir, M.D. (40:34.83)
Yeah, and it matters to have that humility, but at the same time, at least you've heard of it if it was an iPhone, because Steve Jobs got on stage and told you, and nobody's getting on stage in a theater full of people screaming his name and going, depression can be in remission, and maybe that should be a thing we do, I don't know.
Arjun Nanda (40:53.943)
Yeah, that's what it's about, science communication. I mean, this is, I see you posting on the Frontier Psychiatrists, but all of the updates.
Owen Muir, M.D. (40:57.87)
It is.
Owen Muir, M.D. (41:06.062)
It's mild to moderately funny. Not too much. Maybe a little bit more. It's been a fascinating journey writing that thing. So I write virtually every day, maybe one or two days. It's a little bit of a high wire act because I have to write something every day because I tell myself I do and my wife will kick my ass if I don't. Because she wants to know what I'm going to say next.
Arjun Nanda (41:08.439)
So about as effective as a placebo.
Owen Muir, M.D. (41:32.302)
She admitted that to me last night. She's like, I'm really excited to see what you'll say. But sometimes it doesn't work out. Sometimes I'll write an article and I thought the data was going to pan out in a way that let me tell a story that I wanted to tell, and it doesn't. And I'm like,
Arjun Nanda (41:38.327)
That's sweet. Yeah.
Owen Muir, M.D. (41:49.294)
So.
Arjun Nanda (41:50.007)
Some stories have disappointing endings. Or different endings.
Owen Muir, M.D. (41:52.398)
Yeah. And so I try to tell this when I can, but just if it's going to be boring, I'm not going to waste people's time. Most days I came up with something that's mildly entertaining. And every once in a while, just the pressure to say something, well, I wrote a piece on steel cut oats because that's what I was having for breakfast. And it turns out the data on it's fascinating. Like they're dramatically better than other kinds of oatmeal. And Pepsi, which owns Quaker, is behind so much of the bullshit data on.
Arjun Nanda (42:01.911)
Mm -hmm.
Arjun Nanda (42:09.655)
Ha ha.
Owen Muir, M.D. (42:21.166)
on big oats. Instant oatmeal with sugar is garbage. Sugar is poison and steel cut oats are way better. And I had no idea until I sat down to write an article about something, comma anything.
Arjun Nanda (42:36.599)
Okay, so after this, I'm gonna put this article, this one in the show notes, so please take a look at that one. Yeah. Everyone avoid big oats.
Owen Muir, M.D. (42:43.15)
It's a winner. Steel Cut Oats is a winner. I mean, like, be a, look, do your own research. You know, what I'm doing with that, by the way, is it has convinced me to the degree that that's useful. That I think more of medical training should be actually looking at like what's publicly available. Like you can learn about any drug on the FDA website, what they submit. You can read.
any open source meta -analysis you want, you can learn how to interpret that data, even if you're not a doctor, probably just as well as I can, because it's not rocket science. But if you don't look, you won't know. And if you don't try to understand it, you won't. And so when people say, do your own research, I don't actually mean that in a trivial way. I mean, learn how researchers look at research and use that to make decisions for yourself. And that's empowering. And you might not understand it all. And I certainly don't. And so I sometimes fail.
and I'll ask somebody else who understands it better and who I have trust will explain it to me patiently and I'll learn a new thing and repeat.
Arjun Nanda (43:49.335)
So you clearly wear a lot of different hats here as a psychiatrist and advising for a lot of these companies. And you mentioned before that you have bipolar disorder. You also wear the hat of a patient. So if you wouldn't mind, can you talk a little bit about how that changes the way that you actually practice psychiatry and the work that you do?
Owen Muir, M.D. (44:18.51)
Yeah, so first off, I mean, it probably got me to not do it at first. In college, I very intentionally didn't take any pre -medical classes because I was worried that my experience of depression would come back and ruin my ability to be a doctor. And it stood in the way, and it wasn't until I had a therapeutic relationship with a doctor who convinced me that I probably could do it.
and I believed him and he's still my doctor to this day. So that relationship over time, that matters. And my experience of having someone say, even a, I remember, I don't drink, right? I never have, that's life advice. Don't do that and things go better. But I don't drink. And I was worried in my twenties that I would never be able to meet somebody because everyone drank and I was the odd man out. And my psychiatrist looked at me and said flippantly,
Arjun Nanda (45:04.951)
Yeah.
Owen Muir, M.D. (45:17.678)
AA. And not that I'm going to go necessarily meet people in recovery at AA for it as a dating strategy, but the absurdity of, there's a whole cohort of people I have not thought about, was just it loosens stuff up for me to think about. And, you know, I eventually married someone who does drink sometimes, and I don't care, because you don't have to, like, right.
Arjun Nanda (45:20.535)
There we go.
Arjun Nanda (45:39.671)
Mm -hmm.
Owen Muir, M.D. (45:43.374)
But get just finding that relationship that helps you get online matter for me. I think my bipolar disorder has been helpful -ish. Actually, I think psoriatic arthritis, which I also have, has been much more helpful. Well, so I developed psoriatic arthritis probably earlier, but I got the diagnosis in fellowship right around the time my children were born.
Arjun Nanda (45:58.839)
How so?
Owen Muir, M.D. (46:09.166)
And if you want to have two formative experiences for yourself as a child psychiatrist back to back, it's get an autoimmune disorder and have twins. And so, you know, I think the humbling thing there was like, I thought bipolar disorder was going to be my big problem. And so when I see people with mood disorders, especially on the first episode diagnosis, I'll say, I've got great news. You're going to have much worse problems than this, which they're not expecting, right? The...
Arjun Nanda (46:17.687)
Yeah.
Arjun Nanda (46:37.815)
That's reassuring.
Owen Muir, M.D. (46:38.766)
Well, it's not, but it's not in a way that's absurd and a little bit like dark funny, like, because they're all worried about like, my gosh, am I going to have kids? I'm like, yeah, and what if your kids a nightmare? Or what if they get sick? Like, you've got bigger fish to fry, I promise you. And that is not what people expect. And so I think that's helpful. The thing about the autoimmune disorder, which has been interesting and useful to me as a clinician, is it's taught me.
Arjun Nanda (46:41.015)
Yeah.
Owen Muir, M.D. (47:06.798)
kind of on a day -to -day basis, I don't really know what to expect with my immune system. And so I've had to take, you know, immunologics, et cetera. I was just in London and I lost my vision in my right eye for a day because I had uveitis.
there are problems that are not my mood disorder. That has frankly not been that much of a problem, honestly, like it's gone relatively well, because I got TMS and it worked. The mood disorder has been kind of a rounding error compared to, you know, I've also exposure to trauma from my work as a doctor and stalking and that sort of thing. And so that's a problem. So the problems we start out thinking are going to be the problem.
Arjun Nanda (47:42.583)
Yeah.
Owen Muir, M.D. (47:47.566)
that we kind of build our life story around, which many patients do, are not necessarily the problems that will actually get in the way over time. And so I think what I've learned is my role as a physician is to walk with patients through their problems, whatever they may be, with some sense of equanimity and hope that it can get better.
Arjun Nanda (48:06.903)
Well.
Owen Muir, M.D. (48:07.278)
It might be very hard. And I don't know if you're going to make it, but I'm here if you are. So let's see what happens.
And yeah, it works. I mean, the hope I get that really keeps me going is from the perseverance of my patients. They are remarkable. And their willingness to keep pushing is what keeps me willing to keep pushing with them.
Arjun Nanda (48:18.999)
That's so powerful.
Owen Muir, M.D. (48:40.302)
Yeah, if we were just to accept the hopelessness that we see in front of us at first, like no one should do this. But it's kind of a trip to see people get well and do awesome stuff. I was looking at some LinkedIn the other day and I saw a former patient get a major job at a regulatory agency. And then I have other patients who've gone on to do remarkable things. And I couldn't be more excited to see their success. And it's just, it's a trip to get to like,
Arjun Nanda (49:10.879)
You did it. Yeah. Yeah. Yeah.
Owen Muir, M.D. (49:13.326)
Yeah, they did it. I just got to watch and, you know, look, I said it might be okay and it was awesome. My job was to say it, you know, it's possible that it could be better than this. I have some hope for you. I don't know, you could still screw it up if you're me. And, you know, people routinely are great. Like I, patients are the best. I couldn't imagine more of a blessing than having the patients that we get to see us again.
Arjun Nanda (49:25.431)
Yeah. Yeah.
Owen Muir, M.D. (49:43.31)
Maybe rheumatologists have it easier, but I doubt it.
Arjun Nanda (49:45.943)
I'm biased as well. I think, yeah, we do get the best patients.
Owen Muir, M.D. (49:52.91)
And like, that's, I mean, it's just awesome. Like we get to see awesome people who are, you know, proving to themselves in the world every single day that nothing will stand in their way.
Arjun Nanda (50:04.631)
Yeah, I love that. Well, just for some final thoughts, I'd love to just get your vision for the future. What you see, you know, the next sort of frontiers for psychiatry. I know that we've talked a lot about TMS and some other interventions, but what are your hopes? What are your moon shots?
Owen Muir, M.D. (50:25.39)
Yeah. So I hope we think about psychiatry a lot like we think about parachutes. Parachutes have to work. We don't have sham parachute studies. That wouldn't be ethical. But where you land matters.
So I want more wildly effective treatments, parachute level effectiveness for not dying after falling out of a plane and figuring out where you're going to land crucial.
And so it's a frame shift from, well, you broke both your legs. That's OK. I'm like, no, I still can't go anywhere.
Arjun Nanda (51:09.687)
Well, thank you for coming onto the podcast. Thank you for all of your wisdom. It's been such a pleasure having you on here. And I wish you the best and I'm excited to see where everything goes with all the companies that you're working with and with TMS in general. And yeah, it's been a pleasure.
Owen Muir, M.D. (51:34.414)
Brain stimulation is at least part of the future and people can read along at the Frontier Psychiatrists, because it's a fun newsletter and video and podcast and all sorts of other stuff. The one today is actually pretty funny. My favorite section, just for people who like weird stuff, is I have a whole section called the Lord of Liability, which is imagine discovery in the lawsuits that happened after the fall of Sauron and Lord of the Rings. I did a press release from Sauron and Gollum together.
Arjun Nanda (51:44.919)
Absolutely.
Arjun Nanda (51:58.359)
Ha ha ha!
Owen Muir, M.D. (52:02.99)
talking about how Optum acquired Mordor and then shit -canned the ring. There's a meeting with the new interim CEO of Mordor, Incorporated, chastising his Witch King of Agmar project lead on the One Ring search team for...
you know, maybe not finding the ring. Anyway, so having a little fun with it matters and thank you for having me.
Arjun Nanda (52:29.239)
Awesome, awesome. All right, well, you take care. It was a real pleasure. Okay.
Owen Muir, M.D. (52:34.798)
Like this.