Inside A Non-Profit/Academic Interventional Psychiatry Clinic: Preparing for The Next Wave of Psychedelic Treatments

Speaker 1:
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Ritu Baral:
Hi everyone. Welcome to our series, Preparing for the Trip: The Advent of Psychedelic Therapies. We are at episode one, inside a nonprofit academic interventional psychiatry clinic preparing for the next wave of psychedelic treatments.
Our guest speaker today is Dr. Scott Aaronson, chief scientific officer of the Institute for Advanced Diagnostics and Therapeutics at Shepherd Prat Health System in Baltimore, Maryland, where he has been responsible for developing a research program dedicated to the development of medications and devices devoted towards alleviating the burden of severe psychiatric ill`ness across the spectrum of psychiatric disorders.
Dr. Aaronson, thank you so much for joining us for this first episode of TD Cowan Psychedelic Podcast Series. We're excited to have you today to discuss your work at Shepherd Pratt, and how a nonprofit academic interventional psychiatry clinic operates in the real world, how centers like yours may evolve over the next few years as new psychedelic treatment modalities move closer to potential approval.
To start, could you give us a sense of what your clinic at SP looks like today, what interventional psychiatry treatments you're offering, and can you walk us through what a typical week looks like at Shepherd Pratt, in terms of workflow, treatment mix, and staffing?
Dr. Scott Aaronson:
Sure. Our interventional program actually exists within the Institute for Advanced Diagnostics and Therapeutics, where I do most of my research. And in terms of what we have clinically, it primarily is ECT, electroconvulsive therapy, and TMS.
Curiously, I had funding from SAMHSA to open an esketamine clinic, and the powers that be decided that once the grant support ran out, they were afraid that it would not be financially feasible to continue, so I was not allowed to open an esketamine arm. And what you'll also see is that what exists in the community is largely esketamine clinics are existing outside of academic or hospital situations, just because the margins are so small in terms of making this profitable.
That's actually what we're going to wind up seeing once psychedelics start to roll out. I have a feeling that insurers will be loath to really support things in the way they need to be supported to make it possible at an academic center, that it's going to wind up being much more community-based than academically based.
So our clinic, we've got several different clinicians who will screen patients, decide whether they are a candidate for one of our interventional treatments, be it TMS or ECT. And they're also the clinicians who provide the ECT and TMS services. Would love to have an expanded framework in which we're also including access to ketamine or esketamine.
As well, I've been very involved with the development of vagus nerve stimulation that's currently in discussions with the Centers for Medicare and Medicaid as to whether that will be a routinely available intervention. And obviously when we see psychedelics coming up, we're going to try to be positioned so that we're capable of adding that to the mix of interventions.
Ritu Baral:
Will there be a difference, do you think, in the administration of psychedelics within the framework that you just described, such that you'll get approval from the powers that be, versus why you didn't get it for esketamine when it first came out?
Dr. Scott Aaronson:
Boy, hard to predict. And at times I do find some of the financial overlords I deal with to be somewhat unpredictable. Just given what my stature is within the psychedelic community, it would be a shame if we didn't use that position that I have for the larger institution, and we are starting to have conversations as to what that would look like.
The other thing that positions us incredibly well is we have built out for my research a really incredible series of dosing suites. So, in terms of my real estate, I'm incredibly well positioned to be able to offer this as a service. I think the real question is going to be is what the finances are going to wind up looking like, because there will be a problem in terms of what the required oversight is going to be for the dosing sessions, and what the support is going to be for the preparation and for the post-dosing integration sessions.
Ritu Baral:
Got it. We will go into the logistics that you have set up shortly. But in the meantime, actually going back to what you said about the margins, is that something that can be helped with buy-and-bill, the whole ASP plus sick? Could that expand the margins that you're talking about for academic centers?
Dr. Scott Aaronson:
So basically what has happened within the esketamine marketplace is that the clinics that wind up working out better are the ones that are using the buy-and-bill model, where basically the clinic is becoming its own pharmacy instead of using an outside pharmacy. It's a shame that the margins are really between what the acquisition price is and what the dispensing reimbursement is. And that unfortunately has been true in a number of different clinical settings.
I'm unclear what's going to wind up happening with the pricing for psychedelic treatments. And the other thing to bear in mind is that the esketamine model is one in which we're dosing people, at least at the start two or three times a week for perhaps a month, and then perhaps giving maintenance treatment that may be as often as once a week, may be as infrequently as once a month. And it looks like the model for psychedelics will be less frequent.
So we're probably looking at a model of perhaps two dosings in the first month, and then perhaps not another dosing for three months. It's going to vary based on the molecules and the diagnoses.
Ritu Baral:
So from your perspective working with patients in a real world interventional psychiatry setting, where do you still see the biggest unmet need for patients with TRD, treatment-resistant depression?
Dr. Scott Aaronson:
Unfortunately, the biggest unmet need is the fact that, at this point, only half the people with depression actually ever get any treatment for it. And of the half that do get treatment for it, at least a third of them have difficult to treat depression, meaning that they have failed at least two treatments. And there've been a couple of articles that have come out in the past couple of years that suggest that your odds of responding to a third medication after you fail two are substantially lower than your odds of responding to an interventional psychiatry intervention. In these two studies it was TMS, transcranial magnetic stimulation.
We're going to see the same thing if we were to look at what's your odds of responding to a third medication versus what your odds are of responding to a psychedelic intervention. And a lot of the studies have been looking at folks in that TRD group, folks who have failed a couple of medications.
There are a couple of studies that are looking at a non-TRD population, and will come up with different results and how insurers look at whether how that affects their decision-making is still up in the air.
It is truly efficacy. My whole career has been within the framework of difficult to treat depression. That's what all my work has always been. And the great news is that there's a whole lot of people I can now make better that, historically, I haven't been able to make better in the past 40 years. So that is absolutely terrific.
The problem is what the access is. And while we do have transcranial magnetic stimulation and there are lots of centers around, the centers tend to be within large cities. They tend to be within places that have a more developed medical community, and there are areas of the country that you have no access to interventional psychiatry.
Ritu Baral:
So when you say access, you almost mean more geographical, rather than insurance, or is insurance-
Dr. Scott Aaronson:
I mean both, because geographically there are underserved places, and I think even from an insurance base. So if you look at one intervention that we've got for obsessive-compulsive disorder, an illness that we have very, very few effective treatments for, the vast majority of insurers will not pay for TMS for obsessive-compulsive disorder despite the fact that it got FDA clearance in, I think it was 2018. And here we are, eight years later, and I don't need all the fingers on one hand to count the insurers who'll pay for it.
Ritu Baral:
Got it. When you look across that current interventional psychiatry landscape, we talked about ketamine a little bit, specifically SPRAVATO, TMS, ECT, neuromodulation. What has worked the best, from an operational standpoint, for nonprofit and academic centers? You mentioned that ketamine and SPRAVATO administration has bare bones margins for a center like yours. Is TMS, ECT, is that better? Where are the biggest frictions for administering that?
Dr. Scott Aaronson:
The frictions really continue with some of the insurers. One of the problems is we operate our TMS center within regulated space. And so, the good news is we could bill insurance companies more. The problem is that a lot of insurance companies don't want to pay.
Ritu Baral:
What do you mean by regulated spaces?
Dr. Scott Aaronson:
Regulation means that we get to charge for the fact that we are operating within a hospital setting, that we're not an outpatient setting. And so, we can then charge for the use of the room and the use of the machine, which somebody in a private office is unable to charge for. So we're able to bill more, but that also means that the insurers can say, no, we won't pay for you to have TMS in where we have to pay an overhead cost. We want you to go to a clinic setting.
Ritu Baral:
Understood. Okay. So as longer acting agents, such as psilocybin-based therapies like COMP360, move towards approval, rapidly towards approval at this point, how do you see clinics evolving to support these treatments, that may involve longer dosing sessions, preparation, integration visits, and safety monitoring? Can you address biggest clinical or operational questions? Maybe we could talk about the suites that you alluded to before, the treatment suites.
Dr. Scott Aaronson:
Ideally, and the problem is is there's likely to be a huge gulf between what's actually done and what the ideal delivery system looks like. So I actually am operating in an ideal situation, and I have got four dosing rooms, each that looks kind of like a bedroom with some chairs available. They're all hooked up with closed circuit television. I'm able to record everything, and I'm able to, if I decide to record all the conversation that goes on in my dosing rooms, and there will be a requirement for some sort of supervision during dosing.
Ritu Baral:
In-room supervision or camera supervision, you think?
Dr. Scott Aaronson:
If I had to bet right now, what's going to wind up happening is you will have to have in-room supervision by at least one person, and then a second person outside who's able to see what's going on inside the room. That's my guess. Again, the FDA will make a decision about that the same way there will be a decision as to what level of education somebody who is a dosing monitor will have.
That's been a pretty fraught issue, particularly between the companies who are sponsoring this research and those of us who are doing the research. Those of us who are doing the research are aware that this is a very, very vulnerable time for study subjects. And very rarely, but it does happen, is there will be somebody that will have a problematic reaction to the dosing, and you want to be prepared to be able to reel somebody in.
So I keep what are called rescue medications available, in case somebody has a really bad time. And I want to make sure that I've got people who have familiarity with dealing with psychiatric emergencies. Particularly, it's going to happen more in the post-traumatic stress disorder population, where people are having vivid recall of horrific events that they have experienced.
Ritu Baral:
So this rate might be higher in PTSD than [inaudible 00:13:36]-
Dr. Scott Aaronson:
[inaudible 00:13:36] higher in PTSD and we have to be prepared for this. But one of the things that the FDA has always made it clear that they regulate the drugs, they don't regulate treatment. And what the FDA has required for the supervision of psychedelic study subjects has ratcheted down over time. When I was first doing some of the phase two trials, I needed to have doctoral level folks who were there, and I needed to have two people in the room. Now, I'm able to use master's level folks, and I can have one person in the room and one person outside.
And I think that the drug companies, in response to the clear message from the FDA that they're not regulating therapy, and that what the FDA wants to see is drug effect, not treatment effect. So as a result, they've tried to kind of dumb down what's offered in the form of both preparation as well as support during the dosing, as well as integration.
And what I worry about is the fact that these studies will be heading to the FDA with really a minimum amount of psychological support, which I don't think is what will be the optimum treatment paradigm once these things become available.
Ritu Baral:
So how do you see patient flow in an ideal setting after approval for a psilocybin-based therapy like COMP360? Who do you think will be in the room? Who's going to be on the camera? And does Shepherd Pratt have people like that on staff or will hiring need to be done? Will more rooms be required? Do you need a scheduler, like for ketamine clinics? Thoughts on that?
Dr. Scott Aaronson:
Oh, all kinds of stuff. The problem is it depends on how large a clinic you want to have. So my clinic, I can dose four people at a time. There are some dosing strategies that will only take up two to four hours, and some dosing strategies that may take up nine to 12 hours. And so, you're going to have to figure out what your use of real estate is during that time.
You're also going to have to make sure that you've got enough trained therapists who are able to support this.
The other thing you haven't mentioned that is actually my much bigger concern than some of the staffing problems is, who's actually doing the evaluations to figure out who is eligible for this intervention? Because one of the things that I worry about is, until a couple of years ago, was still consulting to the retreat at Shepherd Pratt, which is our high-end self-pay unit.
And a couple of times a year we'd have somebody coming back from a psychedelic experience in South America, and they'd come back really with a chronic psychotic condition that seemed to have been tipped off by the use of, in South America, largely ayahuasca. And what I have a feeling we're going to wind up seeing, is we're going to see some vulnerable people who've got genetic loading for a psychotic disorder who wind up using a psychedelic and precipitating a dramatically worse psychotic condition than they would've had without the exposure to these drugs.
So what I really worry about is, in the effort to make as much money running your dosing clinic, is I worry about people being indiscreet as to who they're letting into a study.
Ritu Baral:
I was going to go there next because you and I have spoken about this, this idea of appropriate patient selection. Maybe focusing on psilocybin, since that will be sort of the nearest term opportunity here for patients to receive this sort of class of therapies like COMP360, how would you think about screening out, or conversely selecting in, patients in this real world clinic setting? Are there groups, specific groups where you'd be more cautious? And how would you handle that if they truly had TRD that required something that wasn't responding to anything else now?
Dr. Scott Aaronson:
Yeah, I think that the biggest things is you want to get as much historical information as possible, have an appreciation of somebody's illness. The two probably biggest concerns at this point from a psychiatric standpoint, is whether somebody has a family history of a psychotic disorder, particularly in a first-degree relative, or they themselves have had some kind of psychotic experience or have been diagnosed with a psychotic condition. So I worry about that group.
The other group that I think is a concern are folks with bipolar type one. So folks who've got full-fledged bipolar disorder. I actually have a study of 15 patients with bipolar type two. So bipolar type two is a similar illness, but it doesn't tend to have the magnitude of manic symptoms that bipolar ones have. They're folks who tend to have more of a cyclical depressive disorder, with perhaps some increase in cognitive activity, what's called hypomania.
The good news is I did not find that within, and again, small open label study, I did not find I was flipping anybody into a manic or a mixed state, meaning that you had both symptoms of mania and depression at the same time. But I don't want to extrapolate to say that, oh, it would be safe for folks with bipolar type one.
The other thing that's really nice to say is that we haven't seen, and there've been a whole host of different studies with different molecules, all with psychedelic activity, and we have not found a significant rate of persistent hallucinations or psychosis. And I have a feeling it's because the investigators have been reasonably responsible at screening out people who should not be within these studies.
Ritu Baral:
Does that pivot on the previous history of psychotic symptoms? And is the risk-
Dr. Scott Aaronson:
And so, all these protocols have specifically excluded folks with a family history and a first degree relative of a psychotic disorder or bipolar disorder, as well as a personal history of either.
Ritu Baral:
And does the risk factor change whether the psychotic episode was acute and isolated, versus a chronic condition like schizophrenia or psychotic depression?
Dr. Scott Aaronson:
We don't know. And the problem is we really haven't looked at that. What I'm happy to say is I have done, and I have three different papers that have come out looking at very underserved populations. So I have a paper on folks who have failed more than five treatments in the current episode, and find that there is a decent response rate. I've looked at folks with bipolar type two. And I've also looked at folks with chronic suicidal ideation. Those are also folks who are excluded from all these psychedelic studies.
And I'm happy to say that we're not finding, at least within these small open label studies, any significant risk of making these people more ill. But I do worry, when we've got larger cohorts, with people who are not screened as carefully that we may be poking the bear.
Ritu Baral:
Got it. And going back to that safety, what do you think that ultimate REMS requirement will be? And how much are there lessons from ketamine and SPRAVATO? And how much of a burden will that place on academic centers?
Dr. Scott Aaronson:
In some ways, the burden is going to be potentially more financial than it's going to be medical. Because one of the things that happened that made the introduction of SPRAVATO so difficult is, do you have any idea how much insurers were paying? The REMS for SPRAVATO was a two-hour observation period, an observation by medical staff. And what insurance paid for that two-hour period was $10. That's not financially feasible for anybody to do, unless you've got 80 people there, because the personnel costs and the real estate cost is high. And I think that there is a continued cynicism within the insurance community about what the value is of paying for psychiatric care.
Ritu Baral:
Any psychiatric care, not specific to psychedelic care.
Dr. Scott Aaronson:
Not specific to psychedelics, for all psychiatric care. I think that there is a belief that psychiatry is not nearly as important, or as important to pay for expertise, as if you're getting orthopedic surgery or some other procedure. And I do think that we need to have a really concerted effort to educate people as to what proper psychiatric care is.
Ritu Baral:
Got it. And then moving to our last point as we think about true real world adoption, we touched on a number of issues, logistics, insurance, reimbursement, whether through insurance or other means. What do you see, what do you predict will be the biggest bottleneck to adoption of new psychedelic treatments?
Maybe we could start with COMP360, because that's barreling down the path. But then, if there are other bottlenecks specific to other actives, we have a number of developers using 5-MeO. We have a developer moving forward with LSD, as well as other actives. How do you see the near-term bottlenecks across the landscape, and then active specific?
Dr. Scott Aaronson:
There are a whole bunch of different bottlenecks. Number one is going to be the fact that, right now, even without psychedelic treatment, we have a shortage of qualified therapists. So, there aren't enough therapists, we will need to train more people. The good news is boy, there are so many people who are so interested in becoming psychedelic therapists, and there's a whole lot of people trying to own that field. So we will have to train people up.
The other issue is, what is the appropriate reimbursement for this kind of treatment? And we have to make sure it becomes financially feasible. What I worry about and what is likely to happen is it likely will be, once this is approved, my guess is there will be a lag time before the insurers are finally forced into covering this. And during that lag time, the only people who will be able to get it are people who are able to pay out of pocket. And it's likely that the treatment will be $10,000 for a treatment.
What's curious is if you break your leg skiing, it's much easier to get $50,000 out of the insurance company to pay for your surgery and your rehabilitation, than if you've got a crippling depression that makes you completely non-functional and we have a way to treat it.
Ritu Baral:
Understood. With that, we will wrap up. Dr. Aaronson, thank you so much for your time. This is obviously a continuing journey towards approval of the newest therapies for neuropsychiatry that have psychedelic mechanisms. And we look forward to rounding back with you, maybe once we have more answers on the insurance front, and we have more data points to talk about on how real world application can be implemented. Thank you, Dr. Aaronson.
Dr. Scott Aaronson:
Thank you.
Speaker 1:
Thanks for joining us. Stay tuned for the next episode of TD Cowan Insights.