Welcome to Navigating What's Next in Interventional Psychiatry. Thank you for coming bright and early on this final conference day in the homestretch. So today I'm very excited to be here with some of my amazing rock star colleagues, Dr. Owen Muir, Dr. Eugene Lipov, and Dr. Nolan Willems is on his way. So just quickly, our disclosures, I'm the Chief Medical Officer at Ozmine, which is an electronic health record company. I run a practice called Vermata, also on the clinical team as board of directors. And usually when we do interventional talks, we disclose what type of machines we use. So I have a brain sway machine, Owen has a number of disclosures as well, works for Acacia, Vermata, IRX Reminder, has stock in a number of different entities. And also relevant for this talk, does consult to Magnus Medical. Eugene Lipov is an employee at the Stella Center. And Dr. Willems has a number of consulting relationships, including relevant for this talk, Magnus. And he's also on the Clinical TMS Society Board of Directors. All right, so today we're gonna do just a couple of quick polls, just to kind of get the lay of the land. And then Dr. Lipov will be talking about the stellate ganglion block for PTSD. Followed by Dr. Muir, talking about getting these novel interventional treatments paid for. And then finally, we'll have our headliner, Dr. Nolan Williams, talking about SAINT and accelerated TMS. And hopefully, we'll have some time for questions at the end. So hopefully, by the end of this talk, you'll be able to understand a little bit about the stellate ganglion block used for PTSD, learn more about this rapid acting accelerated TMS protocol, where people can get feel well in days instead of weeks to months. We'll learn a little bit about breakthrough FDA status and how that has some implications for payment, including a very important call to action from Dr. Muir. And finally, just think a little bit more about real world evidence and how we can work together to really move this field forward. I think last year at this conference, there was, I think, just one program on neurostimulation. It was mainly on deep brain stimulation. This year, I counted five, so we're doing better, hopefully more, yes. We also have a new neuromodulation caucus. And a number of the TMS manufacturers were in the exhibit hall. Not quite as big as the pharma, but we're getting there. So thank you all for being here for today. I think it's a really exciting time in the field. And hopefully, next year, we'll get to, I don't know, ten presentations be the goal. So please submit if you're in this industry. Just real quick, take a minute, just pull out your phones. We just have a couple of quick polls. Give you a second here. Mm-hm, mm-hm. All right, it should be on the next slide, too. So just please select which treatments that either you've referred patients to or offered at your practice. And you can select multiple different ones. You guys can vote, too. What one are you voting? All right. All right. All right, so it looks like about two-thirds of you have done regular TMS referrals or done that yourself, which is great, and quite a bit of escadamine. A fourth doing accelerated TMS, and then kind of a long tail of everything else. We'll note the stellate ganglion block in particular, only 8% of you. I don't know if Eugene, that was you, okay. So hopefully, that will be a really new thing for folks to learn about. We won't be talking about VNS today, but good to see that at least 20% of you have made those referrals. All right, so what gets in the way of suggesting that you're All right, so what gets in the way of suggesting these interventional treatments to patients? Just write a few words, just kind of get them up on the screen. How long do you want to write? All right, so I'm glad that we're including this thing on insurance reimbursement, because clearly cost is an issue, access, knowledge, my attending, I'd like to unpack that one a little more, stigma, marketing or lack thereof, I feel like Owen may have written the stench of quackery, but maybe, yes, was that you? Okay, coverage gets in the way. So I think we're all here trying to do better by the field. So with that poll thing, there is also a Q&A, so we'll have some time at the end, but if you wanna just type questions, you can also type them there and I'll check that out. So yeah, I think we're all on the same page regarding the barriers. And so next, I will turn it over to Eugene to talk a little bit about the Stella Ganglian block. All right. Thank you. Thank you very much for having me at your beautiful meeting. The last time I was presenting on Stella Ganglian block was in 2015, actually. The first time I represented was at the meeting in 2014. So a lot of things have changed, and based on the survey, I see nobody really knows about Stella Ganglian block still. So hopefully, a few things will change after this. At the end, I have a few publications that were just published in the last couple of weeks, which I think may be of interest. So I'm a pain physician and a sociologist, so this is what I do all day long. I stick needles into people. What I found, it's an interesting set of circumstance, is that doing a Stella Ganglian block, which is basically an injection based on that, affects sympathetic nervous system. It can reverse PTSD symptoms very rapidly. By the end of this talk, I hope, at least some of the audience will start thinking about PTSD as post-traumatic stress injury, which is a biological change. Because in order to understand what we're doing, is we need to understand that there's a biological change that's going on in the brain that is affectable by doing medical procedures. TMS is another one of those procedures you're doing. You're actually changing physiology of the brain. Sorry. Okay, so this is kind of the history of Stella Ganglian block, this presentation from a little ago. So 2008 is my first publication. Following that, it was followed in 2010 in Walter Reed. And then there was an interesting paper by Dr. Alina in 2013 where they took a patient who was severely suicidal for a year. And he was treated by Stella Ganglian and suicidal ideation went away and his PCL dropped from 85 to 17 the next day. So after we do Stella Ganglian block, then we see Horner syndrome. This is not a side effect, this is what we anticipate. In fact, we know we hit the right area when you see this change. So if somebody, any of your patients have a procedure, they go, I have a droopy eyeball, it's red, it's hard to breathe through that nostril. It's not a side effect. This is, that means we're in the right spot. So this was a really good summary from Hopkins and they showed where psychiatric use of Stella Ganglian block has been. So the first time Stella Ganglian block was utilized for psychiatric indication was 1947 in Cleveland Clinic for depression. And it was forgotten. I found that reference years ago in a book that was out of print since 1956. One of the questions, one of the most common questions is what is the risk of Stella Ganglian block? So there was only one large paper written about it. This was in Germany. This was in 1992 by Dr. Wolfie. And this was based on 45,000 blocks that was done. This is before fluoroscopy ultrasound. So we know it's much safer now. Nobody died from that cohort of 45,000. They had seizures in about nine people and they had pneumothorax. Again, it's avoidable with better technique. And with ultrasound, it's much better. So the question, another big question is how does it actually work physiologically? So part of, this is from paper in 2009. So basically the question is what happens? So when somebody has severe trauma or multiple trauma, it produces NGF, neurogross factor, which is a neurotropin that is brought from the brain to the Stella Ganglian that activates sprouting in the brain, which increases norepinephrine levels. And as long as norepinephrine levels are increased, people have PTSD symptomatology. And as long as sympathetic sprouting exists, that condition persists. For example, I treated a patient that was a Vietnam veteran. He had PTSD for 50 years. We treated him and about 30 minutes later, he felt markedly better. And last, we followed him up four years and he was doing well. So what that did, at least what I believe, this is sprouting, demonstrating. What local anesthetic on sympathetic ganglion does, it has a dual effect. Number one, it stops secretion of norepinephrine in the brain and when norepinephrine reduces, which happens in about five to seven minutes because norepinephrine is absorbed in glial cells, symptomatology improves. Secondary effect is NGF reduction has been shown in the right model by putting local anesthetic on sympathetic ganglion and that actually leads to pruning or loss of sympathetic fibers. Thus, local anesthetic lasts eight hours, can give you prolonged effect. This was studied done by Dr. Alkar, 2015, where PET scans were done. He took the sickest people he could find in Long Beach, VA and he did PCL assessment. He did PET scans, then he did stellate and he was able to demonstrate significant reduction in PCL, which was not a surprise, but he was able to demonstrate reduction in amygdala activation. I'm not a neuroscientist, so I really can't speak to those scans, but his neuroscientists say they did. So following that, we have now evolved to the next stage of SGB. So we call it DSR, which is dual sympathetic reset. It's not something we're in literature at this point, but basically what we had, I had a patient who was a sniper and he had severe suicidal ideation, which somehow or other he kind of forced me to treat him, which I was not, I was trying to avoid, I was trying to admit him. Anyway, so we did stellate ganglion block and it didn't work. And at that point I was pretty nervous for him. I took him back to the operating room 40 minutes later, did the second level, which took away symptoms in about five minutes. So it turns out sympathetic fibers start at T2 ganglion that go up to the stellate ganglion and ascend to the brain wave vertebral artery. But 50% of sympathetic fibers go to superior cervical ganglion and ascend to the brain via internal carotid. So when you're doing a stellate ganglion block, to me, you're not doing as much of resetting or reduction of NGF and other associated factors. So at least in our practice in Stella, we do dual blocks all the time. So I think it's a lot more effective. So this is the physiology from Dr. Moore's book. And there's a clear explanation, I believe, where the sympathetic fibers come from. So essentially sympathetic fibers follow the arterial flow. So this is ultrasound of C6 level. And the great thing about ultrasound for me, I did 30 years of fluoroscopically guided procedures, but I switched to the ultrasound because it does a couple of things. One, you can see the blood vessels. On X-ray, you cannot see blood vessel. You can actually see physical blood vessels. You can see longus coli muscle very clearly. And you can see all the fascias. Also, when I'm injecting, I can actually see the local anesthetic spread. So if it starts to go in an area I don't want it to go, I can stop and reposition the needle. And those echogenic needles and good technique gets it safer and safer and safer. It's a beautiful way to do things, especially with someone who's done 30 years of fluoroscopic guided procedures. The latest, or only, decent RCT that's been done so far was done through Fort Bragg, Lensheim, Germany, and Tripler Hospital. And they found, this was published in JAMA Psychiatry, and they found that Stelling-England block, now keep in mind one level, was twice as effective as placebo. It's very difficult to do a placebo study because if you do a Stelling-England block, or DSR, or whatever you call it, people have Horner's. So people know when they had the block or not. So the only way to really do it is you need to do FMR or an objective scanner. We had, well, before I get into that, we were very fortunate to have a funder support the study in NYU, which is being done right now. We're recruiting right now for that. And what we're doing there is, not me, but NYU team, patients get functional MRI, all the assessments, and then they're getting dual sympathetic reset or dual injection, and they're getting FMR following that. So we hope that study will have a very objective, unimpeachable result. People are still having difficulty, I think. It's just a mere fact that only 8% of people here know about Stelling-England block. I've been trying to explain this for many years. I've been to AP, now this is the third time, and we're still struggling with that. Because I think it's a weird thing. Confluence of anesthesia and psychiatry is very strange. But the reason I have this picture of the dog is I was the first one in the world, besides doing stellate for PTSD in the human, I did the first stellate in the world for V-PTSD, which is veterinary PTSD. I do a lot of work with military. Turns out, military dogs' chance of having V-PTSD is about 25%, which is similar to the troops. So this was me doing the procedure under fluoroscopy. Interestingly enough, anybody who is interested in this, I have a YouTube video of me talking about it. The dog did really well, actually. So the question is, what are the symptoms of PTSD or V-PTSD in a dog? It's no different than human. Can't sleep. Change in personality style. They become aggressive. Sounds very familiar, right? Hopefully humans don't bite, but everything else is very similar. And the patient did really well. So whenever people tell me, oh, no, no, no, PTSD, SGB or DSR is only a placebo reaction, I tell them about the dog. So this NYU study I was just referring to, if you're interested, here's the identifier for the trial. It's active right now. So there are a couple of papers that just came out, and I just wanna talk about two of them. One of them is DSM has changed two terms in its history. So the one that was recently changed was gender identity disorder was eliminated and replaced. In 1973, homosexuality was a mental disease. So I think everybody who had this degree was probably a good idea to get rid of it. So is PTSD the next term that needs to be changed? So that's why, that's the pin I'm wearing. We're trying to, I'm trying to change that. So the term was originally designed by Dr. Frank Ogburt. He defined the Stockholm syndrome. So he wrote a letter to the APA in the 90s, and he'd been trying to change the name. And we did the survey to see if the name change actually does anything. And I know Frank very well, thankfully. Amazing man. So this was published in Curious magazine or journal. And basically we found that most people would agree that if you could change the name of PTSD to PTSI, the stigma will be dissolved, especially in the military. And then they will get treated. And we basically could be, and this is some of the pretty pictures, but the bottom line is we found what Frank believed based on his findings. And I think it's an important thing to think about, talk about, because if people can start going to see the professionals instead of staying at home and killing themselves, it could be a great thing to do. So I implore anybody who has the power to start moving, that would be great. Frank is still around, he's 86, but he ran out of steam. So he kind of gave the baton to be a non-psychiatrist. So this is demographic from that paper. And anybody who's interested in the paper, please email me and I'm happy to send you the paper. The last thing that we just published was the synergy between ketamine and dual sympathetic reset or cervical sympathetic block. So we've had, I've had absolute honor taking care of a lot of special forces, Delta Force, Green Berets, SEALs, SOF, Special Operator Force. So I termed this particular method, SOF method, because that's what it was designed for. And the reason I actually started doing it is because I did special forces training briefly for like a weekend. And I did TBI, I was taking down doors with explosives. And I said, my head was really hurting. They go, oh, you're such a wuss using gunpowder, we use C4, our heads really shakes. So it turns out pretty much all special forces, before they get deployed, get B-TBI, blast traumatic brain injury. So when you have TBI plus PTSD, it's a very bad combination. So it turns out ketamine can grow nerve tissue back. It does some good things, some bad things. So we're trying to take advantage of the good things that ketamine does and get rid of the bad things. So if you look at the positive effect of ketamine, it increases hippocampal cell growth. It reduces interleukin-6. The negative effect, it activates BAX gene, leading to apoptosis, loss of nerve tissue, which is obviously bad. It also promotes sympathetic sprouting. If you do enough ketamine, it produces so much sympathetic sprouting, you have arrhythmia. What's interesting is cervical blocks reduce sympathetic sprouting, which is a great thing. And it reduces BAX gene. And clinically, we've seen significant improvement in cognitive function, as well as PTSD symptoms. That's it. Thank you so much. Thanks for having me. All right. So thank you, Dr. Lipov. And I will say, I learned about the stellate ganglion plus ketamine, and I learned a lot about ketamine from Dr. Lipov. And I will say, I learned about the stellate ganglion blocks because at Osman, we work with a lot of ketamine clinics. And a lot of those are run by anesthesiologists. And so I do think that as a field, we really need to think about how to collaborate with anesthesia, right, and how we can work together. And so I'd love to chat more about what works, what doesn't, so that we're not kind of in our own silos. All right. Dr. Muir, you're on. How are we gonna get this stuff paid for? Okay. Can you give me five and two for timing? You can just wait. Now? Oh, God. Dr. Williams is parking right now. Great. Because he has two children, so there are child psychiatry related issues being represented. This is, I'm framing this, I hope, as a psychodynamic talk about how to think about the minds of the other parties we need to work with to get our remarkable novel interventions paid for and how that frames how we take the work we're doing as physicians, as scientists, as industrialists, and bring that to people who are not those things. And so I'm gonna start by providing the simplest possible overview of the U.S. healthcare system. And we really have three separate models for payment in the United States. The first are government payers. And this is Medicare, which is a federal program administered by the federal government and includes mostly people who are older, but some people who are disabled. At the state level, we have Medicaid, which is a completely separate program with completely separate reimbursement, schedules, et cetera. But the three-fifths compromise at the beginning of the country was echoed again when we created our national payment systems. And so there was a compromise. We would let the federal government manage healthcare payments for older Americans, and we would let individual states manage healthcare payments for the underserved and impoverished, and that continues to this day. There's also the Veterans Administration, which is a federal system. TRICARE for the military as well, probably is in a similar but not identical bucket. And so those are the government payers. And they have different incentives than what I'm gonna say next. There are fully funded plans and managed Medicaid plans, which are branded Medicare Advantage. By the way, what I want you to take away is Medicare Advantage is not Medicare. These are different products, and they're using the Medicare brand and the term Advantage in order to sell their product, but they are not the same. So fully funded insurance, you've heard of, anyone here heard of UnitedHealthcare? We don't have a poll for this, but like. Have you heard of Cigna? Have you heard of Evernorth? Same thing as Cigna. Have you heard of Anthem? Have you heard of Elevance? Elevance is Anthem. So it gets very complicated, and my argument is if we don't understand this, we're not going to succeed in getting what we need for our patients and for ourselves. So employers in this country pay big insurance companies. In the healthcare hacker world, we refer to these as Bucca, Blue Cross, United, Aetna, Cigna, Humana, Bucca. We haven't figured out how to put all their other names into it. But the sales pitch from big insurance is we're going to negotiate discounts. My children also have figured out this scam, and so when I say you can have 20% of the ice cream, they say, well, how much total ice cream can I request? And they say, there's no rule about that. I issued no decree. And so they just ask for more and more each time so they can have 20% of more. But they give me a discount on the, right. So would you like, anyone here want a 50% discount on a dollar? I'll give you that. How about a 99% discount on a billion dollars? Anyone? Would anybody like a 50% discount on seven trillion dollars? Right, the size of the discount feels good, but the actual number of dollars isn't really as dependent on the discount as it is on the total number. And so that's kind of the way that fully funded plans manage their deal. And they have what's called a medical loss ratio. And that means there's a percentage of the spend they get to keep as profits by law. So Medicare Advantage plans are taking Medicare dollars and would-be Medicare enrollees who would not have prior authorization, and making them have prior authorization, and letting the payers keep 30% instead of 20%. So it's really complicated, but you really do need to understand some of these things if you're trying to either get paid by them or negotiate with them for the necessity of payment. The third bucket is self-funded insurance plans, where the employer groups hire a third-party administrator, which confusingly might be the same company or part of it as the big payers. United, UMR, if you've heard of that, Cigna can be a self-funded third part, blah, blah, blah. But their medical loss ratio, how much of their health care dollar they're spending, is 100%. So big companies like Walmart, you've heard of Amazon, they pay for all their health care expenses, and they take out real actual insurance on getting destroyed on any given claim. So they have different incentives. Fully-funded plans want to save money, because all of it goes out the door, and they get to keep anything, because they're a company, that they don't spend, if every reason to want to save money. Fully-funded plans have zero reason to want to save money, with very few exceptions that allow them to keep making more and more money. And the government wants to save money, but is limited by the law in what they can and cannot save. So the incentives here for the government, we're thinking about spending less on better health from a plan perspective. But there are humans with thoughts and feelings involved. And so the administrators don't want to get fired for reckless decisions. If you're a government administrator at CMS, your job is to never do anything where someone goes, can you believe Bob did that? And you never, ever, ever want to get called in front of Congress for the thing that you did that was inappropriate. And so the penalty for cheaters, when it comes to government plans, is jail. Medicare and Medicaid fraud are federal and state-level crimes that you go to prison for. And so the reason the government can be as lax when it comes to Medicare as it is, when it says, well, you don't have to give us a prior authorization, is because the penalty is not a clawback. It's a clawback of your freedom. And you end up in federal prison or state-level prison. This is a problem. Jail is separate from prison for nerds in the room. For fully funded plans and managed government insurance plans, which are the same thing at the end of the day, we have a plan incentive. Spend more on worse health and keep a fixed percentage. Now, I'm telling you, and you're not going to believe me, but I'm telling you that big payers, from a balance sheet perspective, can't save money. So saying, we save you money, is a great way to never get your thing paid for by big payers, unless it solves another different problem for them that is also important. Welcome, Dr. Williams. Their human administrators are there to maximize shareholder value. This is their fiduciary responsibility to their shareholders. They are doing nothing wrong. They are doing their job. And it would be wrong to not increase shareholder value. And we need to understand that. Their job is to do so. So when we're selling them something in a field of medicine, which frankly is a rounding error on their balance sheets, we when it comes to what they spend on psychiatric things. But it's not a rounding error when it comes to how it impacts other spend, of which they get to keep, wait for it, a percentage. So it's crucial to understand that the penalty for cheaters in this system is clawbacks, money returned to the payer. But if it costs more at the end of the day for them, well, then that ends up being part of their larger profits. So every time you see a penalty against a major payer, well, that's an expense. And the accountants will move that around. So the total expenses go up. And so, gosh, we had to pay, what, $9 million, which is 0.000009 of what? Look, it's not bad for major payers to have penalties in the millions or even billions. Because UnitedHealthcare, for example, makes $330 billion in revenue every year. And of that, last quarter alone was $4.6 billion. It is a scale of money that we cannot comprehend. To give you a sense, if you paid $1 a meter to go from the Earth to the sun and back, and don't fight with me about the elliptical orbit, this is an average, it would get you to the sun and back for $1 a meter. And you'd still have the profits of UnitedHealthcare in one year left over. It's an intergalactic, interstellar at least, scale of money. And we need to understand that we don't matter, but their incentives do when we're trying to explain things. So talking about the return on investment, talking about compliance, et cetera. And for self-funded payers, they have the incentive to get their plan members well at the lowest cost. And they have a fiduciary duty to their plan members. And the penalty for the cheaters is huge financial penalties if they get it wrong. And so they don't want to buy things that are scams. They don't want to buy things that don't work. And we have been trying to sell them those things, or advocating for payments that may or may not have a return on investment for a long time. These are some of the most astute buyers in health care on Earth. And they are good at their jobs. And they care. So when we're thinking about novel treatments, we have the issue of prior authorization. So the current procedural terminology system, who here has heard of CPT codes? Who owns CPT codes? The AMA. It's a product of the American Medical Association. Every time you use a CPT code, boom, AMA makes money. Who owns the diagnostic codes in psychiatry? The American Psychiatric Association. And we would never say anything bad about their ownership of those. But we have to understand there are incentives here. So the government plans, they are the hardest to change. And they have little pressure on decision makers externally because they're so busy. FDA has money in the door from people who want to get things approved. So a bunch of people work at FDA. And industry pays money to have things go through a regulatory process. One person at CMS is having to decide which of the new things is something that's going to get XYZ code XYZ. It's a lot. It's an unbelievable amount of work for a very small group of people who don't want to get fired. And so CPT codes are a way things get paid for. And that's taking physician rates and turning them into money in our pocket by converting them to RVUs in a proprietary system owned by the American Medical Association. And we have to understand that. The language, the shared language, is a conversion to Medicare rates. Fully funded plans and managed government insurance, Medicare Advantage, these are the perfect treatment financially, is infinitely expensive and completely ineffective from a balance sheet perspective. We can't say out loud that this is morally wrong. But I'm saying it right now. Getting people sicker isn't the right incentive. And so I would argue some of our job when it comes to advocacy is helping align incentives for our payer partners so that patients and physicians are doing things that are the right things to do from our ethical perspective. And those align with the balance sheet of our partners. And so understanding their incentives is important. So the refrain from fully funded plans is we need more evidence. And that's problematic because the bigger the effect size, the sample size necessary to demonstrate it is smaller. So the more important the innovation, the less likely they are to pay for it. Because we're not having just endless statistics majors in decision-making roles. And it would be a different world, perhaps, if we did. I don't know if it would be better or worse. But large numbers are impressive. How many people have gotten this? 30. That's not enough. How many people have gotten it? 3,000. Great. So the number of patients we get through our post-marketing data or through our intervention, et cetera, these things matter. And we need to publish them. And even if you think peer-reviewed journals are a scam, and they're definitely a scam, the market cap is something like $43 billion for just the second most popular company that gets you to review for free and gets you to pay for submissions. But you have to have those peer-reviewed publications that payers internally can say, look at this peer-reviewed publication when they're having their own internal meetings because that's what we're working on changing, is what they get to say to each other internally inside an organization. And self-funded plans have completely different incentives. They need hard dollar return on investment to believe. And so this is a lot of work, what you're looking at. Trying to get anything sold into any of these spaces or getting even reimbursed for your work as a practicing psychiatrist is hard. But just like we need to have a psychodynamic formulation and understand the minds of our patients, and we understand that's more important than just the ICD-10 code or the DSM-5 diagnosis or the CP2C code we have built, we need to understand, we need to take a similar approach to the minds of the individuals making decisions at the organizations that will be making the choice as to whether the good new thing gets paid for. And we want to have a framing on a case-by-case basis. So just like you wouldn't say to a patient who had narcissistic personality disorder, you're so disgusting and I hate you all day long. I mean, maybe you would if you're a very dynamic therapist and you understand that's a challenge and mentalization is true. We wouldn't get paid for because there is an interactive complexity is the answer. We have to frame our arguments. No one wants to make embarrassing decisions that they get paid for. And that's both true for us and true for the humans making decisions at the organizations who decide whether to pay or not pay for what we do. The incentive to say yes is for familiar things and no to new things, because new things could get you blamed for acting reckless and nobody wants to be seen as reckless. The more new, the more skeptical. And so we need to help the buyer of our services look good to their organization, not just be hammered with, look at the return on investment. Look at the savings. Look at how effective. We need to help them make the arguments they need to make internally. And so we need to align incentives. This is a reasonable decision and people will be mad if I say no is what works for the government. For big health, it's going to add shareholder value. Only thing you need to say and support that decision in their world. And for self-funded plans, being willing to go at risk on your fees is the most convincing thing you could say, because they've been scammed before and you're willing to put your money where your mouth is, is culturally consistent. The go to market motion for any new health innovation needs to get to the market. And so for investors and for big companies, traction, the number of people in the market who've gotten the new thing, is used as a proxy for actual evidence or power of evidence. And so we need to pay people to do the things that are necessary to get them to do the things. There are enough numbers that anyone believes it works. The herd mentality is important. You'd be crazy not to offer this new important thing which saves money. Large effect sizes in smaller samples means more enrollment, more patients getting a treatment, especially after it's been proved. The more powerful, the more patients need to get it for them to believe it, because the initial studies will be smaller. And so I have some calls to action for you, which will set up Dr. Williams' talk. One of them is to understand that there are opportunities in certified community behavioral health centers to advocate for compliance. They get money from the government in helping them meet their HEDIS measures. Write that one down or get it in the on-demand meeting. But the health care effectiveness data and information set and the merit-based incentive payment system is how they get to keep that money from the federal government. And if they're not meeting their HEDIS measures and their MIPS, they are not going to get to keep getting paid. So when you're selling in those settings, focus on the things they need to do to get paid. Similarly, Big Health loves HEDIS measures, because that is how they get to keep massive contracts. And self-funded plans want to know you're going at risk. The most important thing I'm going to say today is, as of a couple weeks ago, the new technology add-on payment, NTAP, so Google N-T-A-P open comment period. And you'll see there are a number of new technologies that are eligible for additional payments. So they'll happen even in inpatient settings. It turns out inpatient psychiatry is paid for by not just one, but two completely different systems compared to general medical hospitals. And so if we want anything good or new to happen there, as of several weeks ago, now it can, but we need to go to CMS.gov and submit an open comment on a proposed new technology add-on payment, which I strongly encourage everyone to peruse and do. I will note I am a consultant for Magnus Medical, and thus I will not encourage you to specifically comment on that. There are an array of interventions, and you can comment on any of them. But as we saw with the DEA, 38,000 open comments that they legally had to read got things to get the can at least kicked down the road. So our voices can be heard, and those open comment periods matter. And if you're working in industry, build models of your payer partners. Understand their economics and sell in a way that makes sense to them, just like we explain diagnoses and treatment options in a way that makes sense to our patients. Is this going to help your psychosis? OK, yeah, whatever. How about your rap career? Oh, I'd like that, please. So thinking about the minds behind the payers is my advocacy. And if we don't get this right, we're all going to die financially. Because just using Wachovia as an example, it's not officially a psychiatric medicine yet, but senegalatide deployed to 50% of obese people in America would cost 16% of $4.6 trillion. Everything we do doesn't matter compared to less senegalatide for obesity. And the only way we can meaningfully do that is in everything we do, be focusing on important HEDIS measures like metabolic outcomes. And so the better we are at collecting data, the better we are at advocating for what matters to our partners, and the better we are at preventing any allegation that anyone we're talking to did anything inappropriate means success for our patients getting access to lifesaving treatments. Thank you so much. And now. All right. So thank you, Owen. So I live with him, so I hear a lot about this all the time. And one of the things that I've really taken away is that about 60% of companies in the United States are actually self-funded. What, 75%? It's gone up. So a lot of companies, that really means that they have incentives that are more aligned to these newer payments. And so it's something that when we're thinking about partnering, if we can show outcomes, if we can show real-world evidence, working with these innovative payers can then help to make a case to the larger payers that are a little bit more slow to move. So just something to keep in mind and to be a little bit hopeful that we are not on the Titanic, right, if we can work together. All right. And with that, let's pop Nolan's thing out. All right. Dr. Williams, you're on. Thanks for having me, and I apologize for being late. Two sick kids at home. So one is hard, two is, for the parents in the room, pretty difficult. All right, so I'm going to be talking about a biomarker for a new treatment here. And then there's going to be another session this afternoon where I'm going to go more broadly on TMS generally and kind of get into more of the nuts and bolts of how it works. So just to kind of give people a preface for that, here are my disclosures. So I'm going to give you guys a general background quickly, talk about Theta Burst, and then talk about this new technology and biomarker. And so as you all know, depression is a big problem. And we don't have particularly rapid solutions for this problem. The treatments are, on average, slow. They take months to work. And there's not really a consistent anti-suicide effect. Our algorithms for doing this are stepwise. And for some patients, they end up taking five to 10 years of their life to get to a point where they're doing better, because the treatments are, as you know, slow. And the process is slow to get to that next step. We've been very zoomed in on solving a particular problem within the inpatient setting. And so this problem that in psychiatry, as you all know very well, as you escalate the acuity of care in the rest of medicine, you escalate the number of tests and treatments. So if I start having chest pain here on stage, hopefully one of you will come up and help me. Maybe you have an aspirin in your backpack. You'll give me that. And then you'll get me over to the emergency room, in which case there are more tests and more treatments. If I am, in fact, having a heart attack at that time, they're going to bring me up to the ICU, in which there are more tests and more treatments. In psychiatry, as we escalate care, as far as biological treatments go, you escalate care. You lose treatments, on average. And there are no tests, right? So you may say, oh, what about ECT? But if you look at the national average, 10% of US psychiatric hospitals have ECT. Only one out of seven people in those hospitals receive ECT. And so you're really talking about 1.5% of Medicare or Medicaid eligible individuals who could get ECT actually get it. What that also means is 98.5% of people who are sick enough that their insurance companies will pay for ECT don't get ECT. And there's no standard of care for this problem. And so we've thought a lot about how to engineer treatments. And again, I'm going to bust through this all pretty fast and have a pretty detailed talk on this afternoon. It's like an hour and a half. And so we've developed a technology over time that really is more of a pharmaceutical company than it is a given treatment. And what I mean by that is transcranial magnetic stimulation as a device is capable of providing a host of treatments. And there are three domains that you think about when you think about neuromodulation. The first one is, where are you stimulating? The second one is, how you are stimulating? And the third one is, how much are you stimulating? This is a common feature that we'll go through here and later on this afternoon. And so this idea that the device is more like a scalpel than it is like a pill. And that the first set of treatment parameters or the first kind of treatment, if you will, was just the first engineering step to getting this further and further along as what we think to be breakthrough treatment. And so the first step developed in the mid 90s was based off of this idea that the TMS device is like a telegraph, right? Everybody familiar with a telegraph, you know? So you have one end of the wire, I have one end of the wire, right? I can tap on it and you can hear the tap. That doesn't come with any information. That's just simply to show there's a connection, right? So the studies in the mid 80s demonstrated us that we could send a piece of information, you could receive it. The second thing, the second kind of innovation in the mid 90s was this idea of Morse code, right? I can send information to you and you can receive it and you can translate it. In this case, the TMS device is us as users of the device in the case of clinical application as physicians sending a information signal into the brain and that person's not receiving it in their conscious awareness or in their sensation, but their brain is receiving it as a piece of information that bypasses all of that, right? You're sending it directly into the brain and you're sending information to a specific brain region to do something. And in this case, that specific signal was turn on, stay on, remember to stay on, right? And that signal was sent into the part of the brain, prefrontal cortex that's involved with mood regulation. So that part of the brain that folks were seeing in the mid 90s to be underactive. And so if you wanna send a signal directly into the brain and say, hey, underactive area, we want you to turn on, then in some of these cases it did. And what they found was just like my kids, when I'm trying to tell them to do something or not do something, I need to tell them more than once. I don't know if anybody else has had that experience, right? That you have to, with TMS, tell the brain multiple times to turn on. Shouldn't be a surprise, right? And so, you know, the old parameter set or this kind of first treatment, if you will, from the pharmaceutical company that is the TMS device worked, but it's slow and it's very inefficient, just like the telegraph, right? And with that, we were still able to get about a third of people in remission and another third responders, and the third third in open label studies don't improve. The second kind of innovation in this is this idea that you can send a more efficient signal into the brain, one that is more native to the brain's own biology. And what's useful about that, if you think about, you know, if I'm sending Morse code in a different language and then you've got to translate the Morse code and then you've got to translate the language, that's very inefficient. Now, I'm sending the Morse code in the same language, right? In this case, I'm sending the brain's own language back in and saying, remember this, right? And so with that, you have, you know, order of efficiency more, right? So it's about one twelfth the amount of time it takes to send it in. It's about one sixth the amount of pulses when you emulate the hippocampus' own rhythms. And what that looks like is a triplet burst at 50 Hertz every fifth of a second, which is exactly what the recordings in the hippocampus look like, right? And when you do that, you do about two seconds of stimulation with an eight second inter-train interval. And what that does is that increases cortical excitability after three minutes. So you can change the brain's activity in a short period of time. And the Canadian teams that were looking at this as an application with a standard kind of six week course in depression found it to be non-inferior and that led to an FDA clearance with this parameter set here. And so what we said is we said, okay, we now have this much more efficient signal based off of mammalian brain biology. Can we reorganize the stimulation in space, time and dose, as I was describing earlier, to send a signal in that kind of locks in the change you want over a much shorter period. And you're gonna do that as a goal to speed up the response because as you all know, and I said earlier, treating people in these high acuity settings, you can't do that over two months. You gotta do that over less than a week, right? Because the hospital setting is set up to treat people in that sort of timeframe, right? And so we had to kind of go back to first principles and ask the question of, well, what's the unit, right? What's the unit of stimulation that you need in this data burst pattern? And that unit is less than 100% motor threshold, less than the kind of person's cortical excitability set point for about 1800 pulses. So that's the unit. Then we give that unit, you know, folks have given that unit once a day, that kind of standard schedule, and they're able to get a separation from sham. But then the second question when you do that and you give it is how long do you have to wait to give it again? If I tell my kid, you need to clean up your room, should I say it again two minutes later or should I say it again in an hour? And the neuroscience would tell you that it's an hour. I'm a kind of an annoying parent, I guess, in this way. But the neuroscience would also tell you that, how many of you have used note cards to study in college? Did you write one, just one down and look at it over and over again and then throw it in the trash? Nobody did that, right? What'd you do? You wrote out like 50 or 60 or 90, right? And you looked at each one and then about an hour, an hour and a half later, you got back to the first one. Is that right? Did I get that right? You intuited a principle of neuroscience called space learning theory. So space learning theory tells you that you have to be exposed to something and then you have to have time for the dendritic spine enlargement that needs to happen in order for you to be exposed to again, optimally kind of engage that system again. And you can have interval increases in those connections if you time it right. And so that second principle of giving stimulation and actually not waiting a whole day, not doing this over six weeks, but rather just doing it at that optimal interval of about an hour, you have interval increases and pick up more and more change. And that's aligned with stimulating with the same parameter set in hippocampal slices in mammalian hippocampus and mouse hippocampus or in psychological experiments or in stimulating with TMS and looking at motor cortex. The second parameter set, how many of you are pharmacologists? You've given a psychoactive drug to your patients. I would assume almost all of you. You've looked at phase one trials and seen that people do these things called dose escalation studies, right? You know, you get two or three or four different doses of the drug and then they figure out the one that's what, the lowest amount of side effects that has the ideal outcome or if it's a really high side effect burden drug, you make a decision about where the sweet spot is, where it's safe and it's good enough and you don't hit that side effect burden, right? TMS never did this, right? There was never a formal dose escalation study. There was a set of assumptions about what would be a reasonable timeframe to get stimulated and what would be a reasonable course length, right? But investigators started asking this question of what do we do with these folks that don't respond? And so they took those folks and they just kept treating them. So this is a graph of people that failed the brain sway pivotal trial and then ended up getting more dose over the next, you know, from week five to week 16, right? So you can see people at, you know, four or five months start to plateau the effect, suggesting, and hopefully I'll show you this again, suggesting that they were underdosed. The third principle is this principle of reorganization in space, right? How many of you would want heart surgery with an average coordinate of everybody in this room's heart place? Like who would sign up for that? Yeah, true, yeah. So, you know, nobody really wants the average, right? You want your brain's spot, right? That makes sense, that's what your brain wants too. And so, you know, this idea that you need to just, not just hit this spot in the dorsolateral prefrontal cortex, but you need to engage the network that's involved in mood regulation. We know that old behavioral ideas that one brain region is the center of any given behavior is out, right? This is brain networks, we're in psychiatry 3.0 where the brain circuit is central to the discussion, right, and so you wanna hit the right spot in that person's brain circuitry. And we know that from multiple retrospective studies where they've looked at placing it with that average skill spot and then measuring to the ideal brain spot. The closer you are to that ideal brain spot, the better antidepressant effect you get. We did this prospectively in all of our work where we actually used something called hierarchical clustering to take every single voxel in every region of interest in every person and then cluster it to make sub-regions and then we make a decision based off of the interaction of those sub-regions and outputs to target. And we end up with a protocol that's optimized for placement, dose, and timing. That's the protocol. It's another way of thinking about it, a reorganization in time, space, and dose. We had a randomized controlled trial that led to ultimately FDA clearance, so moderate to severe severity, moderate to severe treatment resistance, and 50% of people were on disability for depression. Their average length of their current episode was nine years, so these were folks who'd been depressed for nine years before they got to us, mid-20 year total lifetime depression. And they came in with mid to high moderate scores and these were our response rates on the bottom. Cohen's D effect size is 1.3 to 1.9 for each one of those time points. It was statistically significant no matter how you look at it. And what's interesting about this is if you think about TMS, and I told you before, remember the Morse code, the telegraph story, right? If I ping, you receive it, right? This idea that TMS isn't just a treatment possibility, it isn't just a tool for treating, it's a tool for mapping and understanding the brain, right? And so if I'm wanting to understand a network, I can do this idea of perturbation mapping, right? I can push on a system and then I can look at that push, change something about the system and then I can look at the behavioral change. And then I can associate the behavioral change to the push and it gives us some sense of causality, right? So Anish Mitra, one of the postdocs in the lab was in Marcus Rakel's lab during his MD PhD, he's working with Karl Deisseroth for his mouse work and he's working with us and I don't think this guy sleeps but that's okay, he's doing a lot, he's very good. So he came up with a simple idea that's kind of revolutionary back in his PhD, which is that if you look, and this is kind of hard to see, I'm gonna shout, if you look at this, do you guys see the blue? The blue is because it's kind of right in front of the orange do you see that? So that is two networks, that is two nodes in a network and that's the blood fluctuation in that, each one of those nodes, that blue network slightly in front of the orange. In the old way of thinking about this imaging, you just average the two and say it was a network, right? But that loses some information. So he went back and said, wait a minute, actually the blue, if you do this parabolic interpolation, which is this deal right here, and you actually interpolate where the peak would be, then you get this consistent finding in normal healthy controls that that dorsolateral area that I showed you earlier that's underactive, that's kind of not as governing of the cingulate is actually in normal healthy controls in front, right? Temporally in front and the cingulate is temporally behind. When you take this tech and you stimulate people and you look at the post scan on these individuals after they receive SAINT, what you see is you see the same thing. You see that the dorsolateral prefrontal is in front of the cingulate. And the change in the moderate score in the cingulate lag is correlated. And this was replicated with two different data sets. If you take the pre-scan, the depressed individuals, and you contrast them on normal healthy controls from the same scanner, what you see in depression in some depressed individuals is that the cingulate is temporally in front of the dorsolateral and the anterior insula, right? If you take that same depression data and you get a whole new set of normal healthy controls from a different scanner, how many of you have done neuroimaging studies and realize that's like a scary story, right? You're like, wait, no, it's a different scanner, the different artifacts, the different problems. You're never gonna be able to do this, right? Different scanner, same finding. The cingulate is temporally in front of the dorsolateral and the anterior insula, but in some individuals. But what's cool, right, is that it's only present in saint responders, not in saint non-responders, right? So the people that didn't respond don't have it and they look like normal healthy controls. The contrast between the responders and non-responders is the same brain regions as the contrast between the depressed pretreatment folks and the healthy controls, right? 10 people walk into the primary care doctor's office with polyuria, polydipsia, headache, and vision change. Not all of them have diabetes. Most of them do. The ones that do respond to insulin and their blood sugar looks like the ones that don't and the healthy controls in the waiting room. Right, and you know, this is evidence that we're headed into that reality where we actually have a test that can triage people. So we're really excited about this. Thank you for spending the time and I couldn't do this without all of our superstar students and staff and collaborators and past folks and all the funding that we've received from foundations and everybody that's kind of believed in this work. So thank you very much. All right, so thank you, Nolan. And if folks have questions, feel free to make your way to the mic and we'll take some questions. I actually have a question for Nolan before I get to the audience. So for this kind of moving towards a biomarker, what are the kind of next steps before that could be kind of ready for primetime? Yeah, that's a great question. So, you know, we were fortunate enough to have the National Institute of Mental Health kind of believe in this general approach and they've funded us to do a bigger SAINT trial and then do 10 scans per patient, you know? So if you think about it, anybody ever have those old flip books where your kids have the flip books, right? Where you flip the book and you can see the man bicycling, the woman bicycling through the page, you know? Or the other book, you know, the other kind of old way of looking at a book is the pre-post, right? You see the person jumped and then they're in the pool or whatever, right? And so we're trying to capture the flip. We're trying to capture enough pictures that we can, it's like a little movie, right? That we can see that change flip, right? And I think that's gonna be mission critical to this is not just seeing this thing directionally flip, the temporality of it flip, but actually seeing it flip in real time. And so, you know, and we think that that's gonna be, you know, mission critical for the regulatory process as well. It's TBD, is this something that flips in ECT and, you know, psychedelics and ketamine and normal oral antidepressants and psychotherapy and all that sort of thing. You know, these are all, you know, open questions. It's just very narrow right now, so. Maybe for Owen then, thinking about from a payer perspective, how do you think they might look at something like this? Does this add shareholder value? And how would they determine? I think it does in the sense that, you know, you triage people who have low probability to get better to not have to go through a week of very intensive treatment so maybe in that way it would. For which subdivision? That I'm responsible for, right? So it ends up mattering, right? The emergency medicine service line is different from the inpatient medicine service line, is different from the inpatient psychiatry service line, is different from the other inpatient psychiatry service line, is different from the outpatient psychiatry service line, is different from the PHP rate card, is different from the neurologist payment, it's different whether neuroradi, ugh. And so trying to get a sense and making an argument that helps them place these new interventions in the right cognitive bucket. Is this an interventional radiology procedure? I don't know, but it sure sounds like it. There's a scanner there and somebody's gotta look at something and do something, maybe it's a med device, I don't know. But the argument that's gonna make sense to the person who has to say yes is the argument that matters because at the end of the day if our patients don't get access to these things, none of us win and we have a question. Thank you for the excellent presentation. I have questions, Dr. Williams. So I'm thinking that the dorsolateral prefrontal cortex activation causes also rebound activation of anterior cingulate cortex during the procedure. Can you repeat that? Increased dorsolateral prefrontal activation actually activates the anterior cingulate cortex. Is that right? So one of the side effects of TMS is actually pain. so also anterior cingulate cortex is one of the brain area responsible for pain and emotional pain and also physical pain at the same time can we correlate the side effect of like body pain as a indicator of treatment response like you know herxheimer reaction in syphilis we give antibiotics and we see fewer as you know we can consider that as a response so can we do yeah that's a great question so you know pain there's there's discomfort in TMS at the beginning right yes some people experience it as pain some people experience it as a weird sensation it's it's not really it's not it's not a pain at a level where people quit you know we basically have zero percent people quit at this point for for doing TMS from that from that perspective if you titrate people the right way but you know people do have discomfort at first what you see is that discomfort kind of goes away as the stimulation goes in and then at some point then TMS becomes the antinodosusceptive and so it there are two processes going on the first one is this process that scalp nerves are getting interacted with by the magnetic fields right inducing current in those scalp nerves and that seems to be kind of compensated by exactly what you're saying right which is interactions with the cingulate and kind of buffing up the cingulates role which has a huge amount of opiate receptors by the way and kind of you know some of the most amount of opiate receptors in the brain and you know you know UCSF just had this great paper showing this you know the OFC and cingulate are centrally involved in the pain signals and so this idea that we are sending a signal into the cingulate and having an antinodosusceptive response when the full dose goes in is totally aligned with the idea of why you have some discomfort at the beginning and an anti-pain effect when when the treatment is kind of full-on yeah thank you so much another question there are different types of coils in you know transcranial magnetic stimulation it affects the brain area that we target during the treatment so even though we target the brain area that we are interested in we can sometimes end up stimulate or like under stimulate some brain areas as well so how can we overcome this problem in the future like even though the TMS is more sensitive it's not like ECT I know but sometimes the magnetic field can also affect the other brain areas besides the targeted one yeah so if you look at you know the 2020 paper where they looked at the E field as it related to the actual depolarization of cortical neurons right so they put in macaques put in you know 20 or 30 electrodes and then they looked at where the E field is and where the where the actual you know depolarization is and so the E field goes broadly it goes in a lot of the brain you know a lot of the brain right you get centimeters of span the actual center of the coil where you saw depolarization was only 10% of the bigger map of the E field and so you know you're looking at a sub population of neurons that are you know central to that and so I think you know that's one thing to think about you know another another thing is you know TMS is a great first technology in psychiatry right it may not be in it you know probably isn't going to be when my three-year-old is giving talks like this the technology that we're going to be using hopefully when I'm on my you know retirement it's going to be something even probably after ultrasound right but we know like right now ultrasound focus ultrasounds really much more of a focal probe you know and it may be a treatment and other technologies and so I think there's going to be an evolution that's going to get us around some of the physical physics kind of constraints of magnetic stimulation thank you so much thank you all right next question you know how are you sir good one of my one of my past postdocs is a superstar resident at UT Austin now thank you so I have a question about bipolar depression so our TMS was FDA approved for a unipolar in 2008 I was like 15 years ago still not FDA approved for bipolar depression why is that and what can we expect when it is FDA approved when payers will start covering for bipolar depression yeah it's a great question thanks for your question so bipolar depression is tricky right there's been several there's been several failed trials in bipolar depression my hypothesis which is my intuition about it is it's at the wrong time scale because of the nature of the fluctuations of mood you know people just are in and out of mood states at a much higher rate than a standard TRD MDD patient right and so the you know you don't see that the failed trials are 4% remission in the active group 4% remission in the sham group what you see is you see you know high response remission group you know rates in both groups and so you know getting into one of these situations where there may be a ceiling because the natural propensity of this individual is to you know drift out of the that particular mood state into another mood state at the point in which the primary outcome is happening what's useful about doing rapid stimulation approaches and as you know and these guys know you know you can get people well with bipolar depression with accelerated and sometimes in a day I've seen in six hours you know it's like faster than what we see with MDD so the chance that that the oscillation that is the mood oscillation for a bipolar patient isn't that I mean let's the rapid cycling which we wouldn't take isn't that fast right so you can you can kind of I think you can get a positive trial and you can go down that road if you do it in a much faster time scale than the mood oscillation of the illness I want to add about the insurance coverage piece so not to be too cynical but deep TMS for OCD was improved in late 2018 and we still are having coverage issues with that you know in the past year more payers have started to cover that we got major coverage from Cigna which was a big deal part of Cigna's coverage decision was around post marketing data so this would be really a plug for if you are doing these treatments particularly if you are doing off-label treatments like with bipolar the more we can track that information and actually publish it the better we're going to be towards actually getting payers to move but it's quite an uphill battle even for things that are FDA cleared there is a thing that is true which is that bipolar disorder has a fluctuating course of illness and if you want to design a negative trial it's really easy do it in bipolar disorder and have the trial take a while that's the bottom line it is the easiest disorder to design negative trials in and so if you start with an understanding of the context of the illness bipolar disorder comes and goes it is episodic by definition and so measuring things with an episodic impact in a timescale that is in keeping with the natural course of movement of the illness is going to require massive sample sizes but over a long enough timescale nothing does anything in bipolar disorder other than the Sun and stars and moon and night and those are the cycles that determine the course of the illness and that's context that we know yeah I have a great intervention for bipolar depression it's called the spring and if you do the math on the rate of change in light over the course of day the peak of that illness is is for onset of making him rises you know it's gonna be spring we have Pete about peak of onset of depression because the calculus equation that describes the change of rate of sunlight in the day peaks in the second and third week of October we have to understand when the trial enrollment happens if you want to do a bipolar depression study hit that during October second and third week and you'll get more people etc like there are things that are true and we need to take them into account because we have hundreds of years of experience as clinicians meeting with our patients and understanding them and building our studies and arguments around a fundamental understanding that some people suffer more sometimes not others is different than you know your cardiac heart failure doesn't have the Sun and moon cycle a priori as much but maybe I don't know question okay next question thank you I'm so glad you address payment structure and physical logistics as part of this presentation so really we've seen a rise and you know telehealth and remote medicine and you know for example to make a comparison even in the field of nephrology even though that you know home dialysis or if you do in-person dialysis even though they're both covered by Medicare and most businesses are trying to push for home dialysis because you know basically it involves patients to avoid barriers like transportation and it loves to be mobile and also cost less to the system do you see a future where maybe TMS could be delivered at home and if so what might be some barriers to such a future from a perspective so the question is can TMS eventually be delivered at home okay what do you guys think does it add value for our shareholders the average cost of a new drug in medication treatment in 2023 is a hundred and eighty thousand dollars a year average so a TMS device can go in your home for less than that by a lot is there a kickback for the TMS device through the pharmacy benefit manager to somebody oh sorry rebate rebates are legal kickbacks are illegal and so we have rebates is there a rebate XYZ so yeah sure fine we could put a you know goddamn rocket ship in everybody's house if there was the appropriate rebate structure it's not a question of money nothing we do nothing we do as psychiatrists even remotely matters at all unless it impacts something that actually matters for the bottom line so could you do it yeah of course you could we can spend four point six trillion dollars a year already on anything and do yeah you can do that all day long but whose incentives does that align with is the important question if there was a regulatory standard which are free to make open comments on on regulations gov that said you need to have in-home TMS as part of your coverage policy then you'd probably have it overnight because they'd lose their tax-exempt status under 1974's ERISA with MACRA HIPAA high-tech ACA no surprises CA 2021 built on top of it yeah get the right regulation and all day long all of us will have TMS every day for prophylaxis but but but to be fair though I think I'm curious to hear kind of Nolan's answer but when you think of like a self-funded employer group you know you they do do a lot of like on-site clinic type work right and you could imagine a world in which like a TMS machine in a vehicle or to go and kind of do like a mobile thing I think there was some exploration of that at least in Florida so there is something to be said for making a more mobile anecdotally I've also had patients look on eBay not with my blessing but they have found like old machines and people are like you know they're kind of putting this together like hey why couldn't I actually have one but no one what do you think what yeah yeah that's a great question that was the example that I was going to give is there's this you know there are these vans that are set up with TMS devices inside of them I hear in Southern California driving around and going to folks houses and whatnot I mean I think you know we it's a couple of issues right there is it there is a seizure risk it's there for parameter sets that people avoid now it's you know minor but there for the old you know forms of TMS you know knock on wood we're yet to see one for any of the accelerated data bro stuff that I talked about but it's still it's still a problem right and so you you can imagine a scenario where somebody goes into a seizure and you know the physicians know that if somebody has a seizure with TMS the first thing you do is pull a coil off their head right but if this person's giving themselves TMS at home there's nobody to pull the coil off their head so you really have to have a kill switch right and it's probably an EEG that head would have to go be going at home while the person who's getting treated so you know like a you know one of these AI based you know EEG reading devices that could then turn the device off so that's the only way I could have and I thought a lot about this the only way I've imagined that it could go and actually get some sort of FDA you know readout to do this and in the absence of something like that I think it comes with some risk this mobile deal is kind of a good middle ground right where you know you could drive into a neighborhood or apartment building or a prison or whatever and be able to treat somebody in that setting where you had a physician there and you could kind of risk mitigate the seizure piece if I had a magic wand and I could take the seizure piece away yes right if we could take that part of the risk equation away and find a way to do it then of course right because it's like durable medical equipment it's like a CPAP right you could send it home with somebody and if you had a way of doing it then people could you know be treated and as part of their process you know you know at home but it's there's a lot of innovation needs to happen to get us from A to B and by the way it's two orders of magnitude more risky to give someone wellbutrin at home than it is or Prozac for that matter actually than it is to have TMS be done in the home and that's just using older older protocols the risks we highlight are the risks we have to mitigate but if you like what risks are we willing to accept etc XYZ it matters we have to make arguments that take into account the minds of the people bearing those risks all right great question next hi good morning thank you for your talk this question is actually related to the still a ganglion block I'm active-duty military I'm very familiar with the use and PTSD can you comment on its utility for example acute stress reactions and as a preventive measure for that subpopulation that goes on to develop PTSD thanks if I may I want to understand the question better so you're questioning it you question utilization of selling a new block right after an injury that might contribute to acute stress reaction I personally never had access to population that rapidly I've heard through some my friends who were doing as GB's are still getting them blocks out in the field in Afghanistan immediately following and it was a game-changer out there so I'm you know using it acutely it makes perfect sense because as a pain doc the way I see the work when you have a lot of pain and you can do block to stop it the whole wind-up stops so the more time you give the wind up to continue the worse gonna get so sooner you get to the better question hi I have a question about biomarkers in psychiatry there's like different approaches I've seen like the imaging work that you presented and also like you phys biomarkers electrophysiological biomarkers versus like wearable sensors I was wondering if you have any thoughts on like the pros and cons of different approaches or like different ways they might be useful I can take that yeah I mean I I think that you know the way I see our field as far as this interventional space goes and maybe some would argue generally is that we have a lack of tools right we need more tools and so nobody's bumping up against anybody with you know all the treatments that are helping this problem if you go to cardiology you know how many pacemaker companies are there they're all bumping up against each other trying to get more patients or monitoring companies or you know companies to take clots out of the heart or put in stents or whatever it is right so you've got companies their only goal is to take part of a market share of an established treatment here you know we are in a place where where there's an absence of all this you know so from the science perspective it's very exciting right the trainees in the room your job is safe you know what I mean and so the idea that an imaging biomarker is up against you know a wearable or anything like that or like the whole psychedelic story I hear this all the time the psychedelic story is up against this neuromodulation thing or something like that it's just that's not from my perspective a thing right we're trying to put tools in the toolbox we're in like 1940s cardiology and so you know there are going to be roles for neuroimaging based biomarkers I think in high acuity settings and in scenarios where you're trying to map the brain for targeted treatments you know planning other targeted treatments you know in the really severe cases surgery but it's not going to be very useful for moment by moment at home use nobody we're not going to have an MRI scanner but he's home that's not going to be a thing right and so you're gonna you're gonna have the wearable piece really in the phone piece and kind of all that part be a way of signaling doctors or signaling the patient to then maybe escalate their care in which case they may get an MRI they may not they may get a drug or whatever it is and I think that's the way to think about it is this way of thinking about it of everybody's going at this now there's signals from a lot of these devices I showed you one with an MRI scanner others they're all gonna have a role in 10 or 20 years we're gonna be a measurement specialty where we're measuring a lot of this stuff in 10 or 20 years and that's gonna be one of the pieces of it I think so all right we have time for wrapping up just one more question and then we'll wrap up yeah quick comments I'm been in psychiatry 25 years and I just learned TMS telling my colleagues here definitely do it after my initial butterflies I had a patient and for watching her face twitch while I was mapping her I got a little scared I thought she was gonna have a seizure but four weeks later she's a different person she's been diagnosed with depression borderline PTSD what have you and she's doing great at the end of her treatment she said I thought something was wrong with me as a person but actually was something wrong with my brain and this validated her so for anybody who's having doubt about this treatment I would say you know don't I mean it's really can make a big difference in people's lives and I'm thinking that patient would be perfect to advocate for us at the insurance level you know the payers you know to say listen this is a testimony to this treatment so that's all I to say what a great note to end on and want to thank everybody for being here today if you're interested in getting more involved in the interventional space I encourage you to join the neuromodulation caucus it's a brand new caucus dr. Becca Brindel really pushed for this and go to the APA website and join also check out the clinical TMS Society a lot of great resources webinars and thank you so much for coming today

interventional psychiatry

stellate ganglion block

PTSD treatment

transcranial magnetic stimulation

TMS

depression biomarker

Theta Burst Stimulation

Dr. Owen Muir

Dr. Eugene Lipov

Dr. Nolan Williams

insurance reimbursement

treatment efficacy

patient access