Speaker 1  00:00
Alex, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University, College of Pharmacy. We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider.

Narrator - Dr. Abel  00:29
And now on to the show.

Dr. Sean Kane  00:31
Welcome to Episode 36 of HelixTalk. I'm your co host, Dr. King. I'm Dr. Schuman, and I'm Dr. Patel. Before we get started with today's episode, we wanted to have one brief amendment to our previous episode, Episode 34 that was actually emailed from one of our listeners.

Speaker 2  00:45
And the email was about that we mentioned the conversion from Lantus to Toujeo, which is one to one, but we overlooked the conversion from Toujeo back to Lantus, so the Lantus to Toujeo is one to one. But if you're running into formulary issue and you want to switch patient back to Lantus, you should do 80% of the Toujeo dose to equal, equalize the Lantus dose.

Dr. Sean Kane  01:11
And the typical scenario for this would be someone who's on Toujeo as an outpatient but gets admitted to the hospital, and if the hospital only has Lantus, this is where that 20% reduction or 80% conversion would play a role. Absolutely So with that, we'll go ahead and jump into today's episode, which is talking about some new or novel agents for schizophrenia and Dr. Schuman. I'm sure that this is right up your alley with kind of your expertise here.

Speaker 3  01:35
Yeah, we've been fortunate. Well over the last few years, we've had a number of medications for schizophrenia, looking back to Fanapt or iloperidone or asenapine or Latuda, Invega and Saphris, and then it's been a little silent in the last couple of years. In terms of truly new molecules, we've got a couple new ones that have come out really within the last few months, just to have a discussion about.

Dr. Sean Kane  01:57
So before I know that the listeners are on the edge of their seat to know about some of these new antipsychotics, but before we get there, I think it would be beneficial to kind of briefly review some of the receptors of interest, if you will, in schizophrenia, and what we're trying to do with those receptors. Sure?

Speaker 3  02:11
What we know right now is that there's an imbalance in the dopamine levels. We know that in certain areas of the brain, in the front of the brain, it appears to be a little bit too low, leading to some cognitive symptoms, and then in something called the mesolimbic system, there's an overabundance of dopamine, it would seem. Now, as far as why it's like that, there's some some question or some theories, but as far as we understand that's that's where we're at, and how we treat these symptoms is with dopamine blockers. So the old standard was our dopamine block effectively took a sledgehammer with something like haloperidol or Haldol, blocked pretty much all of these dopamine two receptors, and then we knocked it out. But what that did, though, again, is we lowered the dopamine in the front of the brain so we're potentially either worsening or at least not treating certain other cognitive symptoms, or also we call negative symptoms, more like depression symptoms. And so we're looking, we're looking at other mechanisms, and then we have this newer one we added really, and probably more like in the 70s 80s, about blocking serotonin receptor five, HT two. And so that combo is what we call now the atypical, or the second generation antipsychotics. And that's where we've been, pretty much, with the exception of Abilify, which is a partial agonist at the dopamine two receptor.

Dr. Sean Kane  03:26
So what you're saying is that typical antipsychotics, like haloperidol were primarily dopamine two or d2 receptor antagonists, so they blocked dopamine everywhere, and it was kind of a very heavy hitting dopamine blockade. Whereas our atypical antipsychotics, in addition to having that d2 blockade with dopamine, they also added blockade of serotonin in the form of five HT to antagonism, right?

Speaker 3  03:49
And so what it did is it was they were able to be less harsh on the dopamine receptors and kind of spread out to different other receptor profiles, so you can still get a calming effect and maybe some anxiolytic types of behaviors on from other receptors.

Speaker 2  04:04
So if I remember correctly, when Abilify, aripiprazole came out in the market, it was more about it wasn't a complete antagonist, but it was more of a partial agonist. So it sounds to me like it tried to kind of balance the amount of dopamine you have in the brain. Is that correct? Dr. Shu, right?

Speaker 3  04:21
And so that's what we're going for here. And so the concept is kind of cool. I think of it as you know, if you think of a slow driver in the fast lane, where we're still going to get where we're going, and we're just kind of slowing things down a little bit. And that was the idea with with Abilify here, was that it is a partial agonist if it's in the presence of something that's dopaminergic, or in dopamine that's high, it's going to lower the amount, but still better than nothing. And then in areas of the brain where there's no dopamine, so theoretically, in that frontal area of the brain, it's going to increase it a little bit. And so again, you can just kind of balance that all over. And that was kind of the theory with the Abilify and it's it was in. Know, which, again, worked for some individuals, but admittedly, there were some patients who still needed a little bit more of that dopamine blockade. And so for some of those people, then maybe Abilify was even too much dopamine, perhaps.

Dr. Sean Kane  05:14
And you know, the the idea of this d2 receptor partial agonist was kind of marketed as this dopamine system stabilizer, that it kind of gave you more dopamine if you had too little, or reduced it if you had too much, which, my view, is a big marketing, you know, push. It sounds really good. Whether that kind of conveys clinical benefit to the patient, I don't know, right?

Speaker 3  05:36
And then there's this whole, and that's where there's this whole, you know, discussion about, you know, learn the role of antipsychotics as mood stabilizers, and some of that, potentially, is based upon their ability to stabilize that dopamine system.

Dr. Sean Kane  05:47
And you know, we're focusing on dopamine and serotonin, but you know, mostly because of the adverse effect profile that we see, we do have a lot of other receptors that are implicated with many of our other atypical antipsychotics, right?

Speaker 3  05:59
And there's a couple of different theories about what is going on, but we do know that there are some risks of dizziness or orthostasis that you can have if there's too much of the Alpha receptor blockade. Some of these medications we know, ones like Clozapine, for example, that you could get that dizziness, and so that's had to be monitored for. But the big ones we think about are metabolic issues, and some of that is argued about by nature of that atypicality of it, so the serotonin receptors, but then it also may be that there are some muscarinic receptors that are targeted as well. And so there's been kind of a move to try to find medications that are still atypicals but have a different profile, so they don't have as many of those metabolic issues. And that's where they've, you know, looked at again, tamping down some of that, that muscarinic activity, or even as much of it, serves an ergic at the five or c2 receptors. So we've had others out there, like Latuda, that have, have tried to do that and done okay at it.

Speaker 2  06:56
So when you compare the new antipsychotics, meaning the atypical antipsychotics, and kind of compare that to the typical antipsychotics, I think the biggest difference we have seen that there are less EPS symptoms, more metabolic symptoms, and actually helps to improve those negative symptoms you talked about and the frontal lobe of the brain as far as the schizophrenia is concerned, right?

Speaker 3  07:17
The problem, though, about improving is it's they have not even all the studies have shown that they improve the negative symptoms as much as they potentially, or at least don't make it worse. And that's, that's one of the issues, again, is, and we're still looking for for new mechanisms there to treat those negative symptoms. All right. So yeah, so we'll start off with the first one of brexpiprazole or Rexulti, and this one, again, five ht, one partial agonist, which is a serotonin receptor that may have an antidepressant like effect. And that one, pretty much like every other medication that's out there, it's got its d2 or dopamine two, partial agonist. So again, like aripiprazole, but a little less giving back dopamine. And then it has the serotonin receptor blockade, fairly similar to other atypicals, it's got some blockade of alpha receptors, and this is where it gets a little bit into the weeds. But also somewhat unique, is specifically something called Alpha 2c and that's one that we've heard about for other medications, we know mirtazapine is an alpha two a 2c antagonist, and we know other medications, we have some medications, guanfacine clonidine that are alpha two agonists for treatment of ADHD, but we haven't quite had one with this specific profile, and so while it is approved now for treatment of major depressive disorder and schizophrenia, due to some of the uniqueness of these alpha receptors, which made people think, at least when I first thought, I thought PTSD treatment. And sure enough, manufacturers thought the same thing. So they're going for indications for PTSD as well as for agitation in a geriatric population as well.

Speaker 2  08:48
And I've seen more and more antipsychotics now being used for MDD, the major depressive disorder. I think this kind of includes quetiapine. Would you say this is really coming from the five HT receptor mechanism and one of those mood elevating effects that you were talking about,

Speaker 3  09:07
I think it's coming from a couple places. One of them is that, you know, in some circles, individuals feel that the SSRIs and our the whole theory upon which it's built upon their use is somewhat questionable. So it's kind of a move, maybe from that serotonin hypothesis of depression to looking at what else is going on, again, looking at all the neurotransmitters that are involved, mood stabilization. And so I think it's a move towards that. And so trying to figure out what other mechanisms do we have to address this potential. You know, again, what we feel maybe an imbalance of serotonin and dopamine norepinephrine, but it's still, you know, contentious at this point. But yeah, it's trying to find a different mechanism.

Speaker 2  09:48
See what it does, assuming the doses are different for both the indication, right?

Speaker 3  09:52
This is one where it's not terribly different. We have a one to our point, five to three milligrams is the is the dosing range for someone with. MDD, and then one to four milligrams per day, with some with schizophrenia, so just a one milligram difference through the indications there.

Dr. Sean Kane  10:07
So as you mentioned, brexpiprazole, or Rexulti, was recently approved by the FDA in terms of some of the clinical trials that got it approved. What are some of the key features of you know, how it was studied and what it showed that really stand out to you it's

Speaker 3  10:21
interesting thus far is that they've only released, as far as I can tell, the placebo study, so we don't quite have any of the head to head studies. Usually they'll pick on either ziprasidone or Risperidone to do a kind of a comparator for these thus far when we have the placebo studies. But what we do know is that they looked at both PANSS, the positive and negative syndrome scale and the BPRS, or the brief psychiatric rating scale, and looked at at baseline individuals who had acute schizophrenia exacerbation. And based upon the population, they include it, looks at it, it was about markedly severe symptoms according to a score of about 55 ish on the BPRS and about 95 on the PANSS. So these integers, again, were not for least psychotic, but they did meet criteria for having symptoms at the time.

Dr. Sean Kane  11:09
That's interesting to me, in terms of the ethical side of this, you know, you have someone who, as you said, meets criteria for schizophrenia with you know, symptoms. Is it ethical to give these patients a placebo versus giving them even haloperidol or some other active agent that is approved for this. How is that okay? In the realm of ethics,

Speaker 3  11:30
it's tricky. So one of the things they do to address it is that these are not individuals that, again, didn't need medications, aren't they? They do, you know, they do a wash up here again to avoid any kind of a withdrawal symptom that can occur. But yes, there is, you know, it's an avoidance of those who are seriously, seriously, seriously ill. And so that can then, admittedly make it sometimes hard to extrapolate these studies to what we call the real world populations who are going to be more treatment resistant and more symptomatic. Because again, in those individuals, it's going to be very, very, very ethically questionable to enroll them. So by definition, then you're going to have individuals who may be able to weather that time without the active treatment. So yes, that is one of the things they do, admittedly, in some of these studies.

Speaker 4  12:15
So I would assume that the drug worked. Then yes. So what they

Speaker 3  12:18
did is they used a few different doses they looked at, they kind of picked a really low dose to see what that did compared to placebo, with the idea that it wouldn't be any different than placebo, and then they chose higher doses. So in the first study, they looked at point two, five milligram, two milligram, four milligram, compared that to placebo, and then what, yeah, what they found was that even as early as week one, the two milligram dose showed significance compared to minimal changes point two, five milligram dose, and both doses end up performing well. But the end result is that the higher doses did have a c3 before four milligrams dose did show the most benefit, and both doses, again, were significant on that PANSS as a primary outcome. The other thing that was good about it was they found that wasn't a huge amount of side effects with it. They did in this study finds that akathisia was more common with the two milligram the four milligram dose, but that actually contrasts to a second study, which found that akathisia was actually higher with placebo, and they did find some weight gain, headache and somnolence. But again, these were not much inordinate amount greater than than placebo. So the issue with that, though, is this is a six week study. We know it a lot of times takes time to start seeing these metabolic issues. That was, I believe one of the issues with medications like Seraph will and Zyprexa is that when you're looking at six to eight week studies, you're not able to see what is going to happen, you know, 369, 12 months out down the road, and that's why we have more stringent metabolic monitoring, where, really, ideally, every year, we're continuing to assess what's going on about that risk of insulin resistance.

Dr. Sean Kane  13:55
So you're suggesting things like lipid panels and a one sees and things like that. And even, you know, weight gain won't be evident unless they have a

Speaker 3  14:03
longer trial period, certainly, and it's sad, but true is that even at this point, we're still, we're really in some in some facilities or some care centers. We're only now beginning to start doing this. And these came from 2005 guidelines consensus were released by the ADA. And so this, we're 10 years into the publication of these guidelines, and we're still saying, Hey, I think we need to actually do this monitoring.

Unknown Speaker  14:26
It's very interesting.

Dr. Sean Kane  14:28
So then the drug works for schizophrenia, and we do see some adverse effects, possibly akathisia, possibly not, in terms of major depressive disorder, MDD, you know, that was the second indication of brexpiprazole or Rexulti. What kind of you know, efficacy and safety did we see in the Depression study?

Speaker 3  14:47
Well, this one was interesting. It was actually done a little bit differently in the study design, so they used it as an adjunct to open label treatment with either an SSRI, so something like your probably. With paroxetine, fluoxetine, sertraline, or use of an SNRI, duloxetine or venlafaxine, and then those doses were maximally tolerated. And then they looked at randomized One to One to One to brexpiprazole at a one milligram dose, three milligram dose or placebo, kept the doses of the antidepressants consistent. What's interesting though is that they ended up kind of changing the protocol partway through there were to include so those that maybe reached or had a response at one point, but not a responder at the end. And so they, they had a potential to include those in in their efficacy analysis. So they ended up kind of changing their protocol midstream. So that was something I found kind of kind of interesting. But based upon the amended protocol, they did find significant benefit with this drug.

Dr. Sean Kane  15:45
And then in terms of adverse effects, what kinds of adverse effects did they see?

Speaker 3  15:49
So the adverse effects here were similar to the up to the other studies, the ones I mentioned, there's some weight gain, akathisia, then addition of somnolence that was available at a dose dependent fashion. So again, we continue to notice that individuals seem to be very unique. Even amongst these drugs that are considered less sedating or with lower weight gain, you can still see certain populations certain images that do get it. And this is just a quick plug for use of pharmacogenetics. Pharmacogenomics as a way in the future, to start predicting individuals within your population about using these medications that we were learning more and more about, that that kind of genetic predisposition that should help guide future therapy with these medications.

Speaker 2  16:28
So we're moving away from typical and going into the atypical realm. But then even an atypical drug like Seroquel has significant issues with Qt prolongation. Was something like that seen in the study for practice,

Speaker 3  16:42
all Fortunately, no. Again, they did not see any of the metabolic issues during this short again, six week study. Did not see the insulin resistance, did not see dyslipidemia and and none of the studies actually did they see any any Qt prolongation, which, again, it that is very nice, because that had been, that had been a big concern. And a lot of the newer ones that are coming out are that way. Lurasidone, Latuda, again, is one that's fairly safe in terms of Qt prolongation. Even Seroquel is not terrible at it compared to those older ones. You know, Risperidone had some problems. Haloperidol definitely had some problems. Especially initially, there was a big fervor over Geodon or ziprasidone.

Speaker 2  17:20
So you mentioned that their metabolic issue or metabolic changes, were not big of an issue with this drug. But you also mentioned that you monitor these patients for the metabolic parameters. How often would you say you monitor them? What is your frequency of monitoring?

Speaker 3  17:36
So what you're generally recommended to do is, is that that baseline you're getting your initial so when you start something on the medication, I want to know what is their weight. I want to know their baseline waist circumference. I want to know their blood pressure. I want to know what is, ideally a fasting blood glucose. But they've said that an A, 1c will count. I want to know what their lipid panel is as well. And then we will go ahead and assess the blood pressure again at four weeks and eight weeks, and then at 12 weeks, we want to go ahead and get everything again. So we want to get the lipid panel there, and then we want to get the fasting plasma glucose panel, and then ideally, we can get some difference in every three years on the lipids and every year on the blood on the blood sugar. But I think it's generally recommended now that you might as well, every year go ahead and get these. So really, that's what we're trying to practice at our facility, is that every year, go ahead and continue to get what is a blood sugar, what is the lipid panel, and keep doing that, because once again, this is not something that okay. You know, if you go a couple weeks and it doesn't pop up, we're fine. This is something that needs to be continued to monitor so and again, you know, due to stigmas with the illness as well as population. Yeah, can be difficult. There can be maybe a loss of follow up in a while. So you want to continue to reach out and catch these things before it leads into full on diabetes, which unfortunately had occurred for individuals in the past where we just weren't monitoring it.

Dr. Sean Kane  18:55
Just to be clear, to go back a little bit, the major depressive disorder indication is for an adjunct, right? Yes, yes. So these patients are always going to be on some agent for depression, and it's not working well enough. So this is an add on for, basically, depressive symptoms that aren't well controlled with an agent that is approved for depression, right?

Speaker 3  19:15
And again, you know, it's always going to be tricky to kind of navigate those you know, in terms of when you use it, most of the time, you're looking at somebody who hopefully has not responded to optimal doses. You know, if we start somebody on 10 milligrams of Lexapro or escitalopram and they don't respond, that's not the generally the time we say, let's go ahead and throw in an adjunct and a psychotic because the dose is too low, right? Again, because the dose is too low, and we maybe even haven't explored other other medications within the class, and so we do, you know, have to really pay respect to some of the side effect profile of these medications, these atypical antipsychotics, they can work very well, but again, they are not. These are not inert molecules.

Dr. Sean Kane  19:54
Let's go ahead and move on to the next agent that was also recently approved, but is also an atypical anti. Psychotic that is approved differently. So in this case, this agent is approved for bipolar disorder and schizophrenia, as opposed to schizophrenia and MDD, then, is that correct?

Speaker 3  20:09
Yeah. So the name of this set, this new one is cariprazine or Vraylar and so this one, like are some of the other ones. It does have some maybe antidepressant types of effects at these five HT one serotonin receptors, and then it's also a dopamine two partial agonist, like your aripiprazole, like your brexpiprazole. But what makes this one somewhat intriguing is it's a partial agonist at the dopamine three receptor.

Dr. Sean Kane  20:35
So what is involved in the d3 receptor versus, let's say, the d2 receptor?

Speaker 3  20:40
This is one that, in the future, it potentially could be, could be used for, again, for treating mood disorders. So it may increase dopamine and acetylcholine in that prefrontal cortex. So again, this could be a way to get dopamine in those areas of the brain that we've had trouble with our previous antipsychotics and mood stabilizers. And so, you know, for somebody lists schizophrenia and those negative symptoms, doctor tell, as you brought up, that may be an option, but the big one, and again, this is off label right now, but the big one is that this receptor has been for the last couple of years, been talked about for treatment of substance disorders and substance abuse. So we've really looked, and we don't have a lot of good treatments for substance abuse, especially those other than alcohol use. So somebody that abuses cocaine or abuses stimulants, and so this is one that there's a lot of talk right now about what that receptor could do, as well as the fact that it may have lower risk of X pyramidal side effects owing to that dopamine three blockade.

Dr. Sean Kane  21:38
So what you're saying is, at least for bipolar and schizophrenia, which is what it's approved for, we see some theoretical benefits for the two, the d2 partial agonist with this particular agent, but at least right now, much of it is more theoretical versus, you know, we see this amazing efficacy or safety benefit that was very different than the more traditional d2

Speaker 3  21:59
antagonists, right? And even, even, to be honest, with both of these medications, I believe that they're also looking to the future. So brexpiprazole, Rexulti does, again, have that calling card of that dopamine, you know, maybe a little less dopaminergic as a part a partial agonist with the less of that intrinsic activity this one may have, that that d3 activity that could make it unique thus far, nothing that would say these are better than anything else out there, but both of these, they're going to get on them. They're get on the market right now to be there, and I think they're going to continue to push them and continue to evaluate them for what, what else unique they can do. And so I think that's the point. So just to be kind of aware for those again, seeing these medications yet. Thus far, we don't really have a lot of info comparing them head to head to any of the existing medications.

Dr. Sean Kane  22:48
So in terms of the clinical trials, as we said, it's approved for bipolar and schizophrenia, obviously the drug works. Wouldn't have gotten the FDA approval for that. What were some of the key characteristics that kind of are big take home points for you. In terms of the phase three

Speaker 3  23:01
trials, one of the things, whether this drug, surprisingly, has been around a bit. There were some. It was originally approval. Was submitted to the FDA in 2013 but then it was denied. They really wanted more studies to kind of determine what's the optimal dose. There was some issue with, once again, akathisia having a number needed to treat, a number needed to harm of seven versus the number needed to treat of six. And so at that point, okay, well, you know, yes, you can treat, you know, you treat bipolar disorder, but same time, there's that risk of a side effect leading discontinuation. So they wanted to go back and do some more dose finding studies. And so what they came up with was a dose of 1.5 to six milligrams. And that's the same dose for both schizophrenia and bipolar disorder, and that was based on with bipolar mania. It was a three week study, so fairly short. But once again, they did a washout phase. Did a dose where they increased it three milligrams on day one, six milligrams on days two, three based on response, and then kind of increased it slowly as needed, from there up to a max dose of 12 milligrams. So they looked at that and the safety parameters and the akathisia rates, and came up with, again, the standard dose at this point to say, that's the point at which it has its benefit and we're maybe at less risk of side effects.

Dr. Sean Kane  24:14
So the big thing that we're worried about then is akathisia, which is something that we saw with other d2 partial agonists like Abilify or aripiprazole, then we also see a little bit of the somnolence, which isn't uncommon with many of these agents as well, correct? And that's

Speaker 3  24:29
going to be something that I believe is going to be, you know, somewhat individualized. You're going to want to look at this medication for those that maybe tend to more somnolence from these other medications. You know, it's likely going to be less than with clozapine, Seroquel or with Zyprexa. But we want to know, you know, if somebody has, you know, had some of that somnolence on Abilify or Geodon or some of these other ones that are less sedating, they may, they may still. May still see it here. So we just want to kind of use caution in those populations.

Speaker 2  24:58
We mentioned akathisia. It's one of the EPS symptoms. The second is, Parkinsonism. Is there any issue in particular with this medication more so than the other?

Speaker 3  25:07
Yeah, so with with Parkinsonism was another type of extrapyramidal symptom that did come up when they looked at the adverse effects. It just said, you know, under EPS, we do have multiple kinds of symptoms, but both akathisia and Parkinson like effects were the ones that were most commonly seen, versus a tardive dyskinesia, which is generally something a lot more troubling that can be very hard to treat. Didn't see much of that, but yes, the Parkinsonism and the akathisia are gonna be ones to continue to watch for with these medications, and it seems to be this kind of risk benefit with medications that are less sedating and more of, you know, some of the tremor or a restlessness that occurs. So that's always something to be balanced out and look at for you know, that kind of specific patient, and see how you know how they've done on other medications that are similar.

Speaker 2  25:56
So how would you evaluate cariprazine with other medications? Where would you put it? In a place of therapy

Speaker 3  26:02
currently, you know, again, at this point, I really would lump it in, still with with aripiprazole, or Abilify, or brexpiprazole or Rexulti amongst and maybe even with ziprasidone or Geodon, with these less sedating atypical antipsychotics, which have a trend to maybe being a little activating, and thus we have to watch for some patients who are used to feeling kind of sedated, and then that the lack of sedation can sometimes leave them uncomfortable. Beyond that, that there's there's really nothing else, there's a lot of these other medications may have that dopamine three receptor interaction as well, and it's never been shown to be a big part of how they do things. So again, you know, it's going to be jury still out as far as what that actually means to this drug, and whether it suddenly elevates it to better, or it puts it in its own niche. That kind of information is going to come for now. This one is on the market. It's an alternative. And again, somebody has failed these other treatments that have been on the market and which we do know a little bit more about over periods of time, as long as they fail those this is certainly something that can be used in alternative but I don't think at this point I would necessarily leap to it above those other ones.

Dr. Sean Kane  27:12
Yeah, and someone who treats no schizophrenia. Given that we have a lack of comparative data, I have a hard time making the recommendation of using brexpiprazole or Rexulti or cariprazine or Vraylar, I have a problem considering those agents, given that we have Abilify or aripiprazole That's been around a lot longer, that we have more long term data with it, and again, I'm not recommending any of these agents, but I do have the recognition that Sometimes, especially with this, you know, class of medications, maybe that longer term safety data is a really good thing to have in terms of supporting one agent over another.

Speaker 3  27:48
I agree, Dr. Kane and again, that combined with with, again, wanting to do subgroup analyzes looking at this, these medications within other other populations, beyond just this, you know, somewhat markedly ill individuals, but amongst those who you know have co occurring substance abuse, among those who have severe schizophrenia, among those with other comorbidities, that's where I want to see this information again, as well as over time data to see about the metabolic risks. How does this compare to other medications? If it's a point which we have nothing else to offer a patient, I would certainly think these deserve a fair shake, and if the new data seems to come out and indicates their place in therapy, because, of course, none of the guidelines are including these thus far, and it'll take a couple years before that place is really developed, then, yes, I would say stick with any medications you have. However, as we learn more about these, potentially some of those off label, theoretical indications may match, along with some of the comorbidities you see, and that may may elevate it a little bit, but we're not there yet.

Speaker 2  28:50
And so these are new medications. They're a brand name, and because there are other proved medications out there, we have more information about it. This probably will be one of the higher tiered medication, meaning more expensive for the patient, but we'll see what the phase four study has to say, and what data that comes up that will compel these insurance companies to put it on a lower tier, perhaps, but that's further to see. So Dr

Dr. Sean Kane  29:13
Schuman, I'm going to put you on the spot here. Let's say that you're in a retail pharmacy and you're filling a prescription for either of these agents, you get three counseling points for the patient that's picking these up. They can be the same ones, or they can be unique to each agent. What are your three most important counseling points specific to these agents that you're going

Speaker 3  29:32
to provide that patient? A couple things. Is the first one, again, is going to be an important one. I counsel with all patients, encourage all students, is, you know, take this medication every single day, even if you're feeling better. That's a very important point for any kind of psychiatric medication, because we sometimes, you know, forget you say, okay, every day you start feeling better, and you almost forget the point in the past in which you were feeling, you know, very sick, or you start to forget about what it's like. Why am I even on this medication? So to continue to take it every single day will be my first. One, and then my second one for that would be, yes, it, you know, due to these extra parameteral effects, I would say, you know, continue, you know, let your provider know if you have and then explain, you know, if you start to notice, maybe, you know, I have difficulty sitting still. I feel like I have to move my arms or my legs. And there is a way to go about it so that you don't put the patient you can, you know, not put patient in distress, because that can be something. This is why I don't want to take this medication. So just to discuss this is, you know, this is by no means common, but it can occur. So if you start to notice feeling that, or maybe noticing that you're a stiffening of your arms and your or your legs, or maybe a shaking of your hands, or if somebody else notices it, then go talk to your doctor. Don't just, just throw the medicine away. We don't want to say that, but just it should. This is something that should promote dialog with your providers. And then I believe a third one on that would would be yes, that these medications do in the in the past, have some issues with, maybe metabolic issues. So to make sure to go ahead and be compliant with, you know, with blood March and to go ahead and you know, we want you back in after about three months, just to see how the medication is doing on it. And we, you know, we actually ideally would want you every four weeks again, get a blood pressure and get some of those readings as well as weight as well. But you know that could be potentially done in a less acute setting, but at least come in, get your labs drawn at those other at the 12 weeks, and then after every year just to see where you're at, and you start to notice, you know, weight gain, if you're concerned about those things, yes, another point in which we should invite dialog with providers. All right, so just to go ahead, the first two we talked about. The first one of these was brexpiprazole, or Rexulti. That is the medication that's similar to aripiprazole or Abilify but a little bit less of the intrinsic dopaminergic activity. And then the second medication we talked about is cariprazine, or Vraylar. And this is a medication that, again, is somewhat similar, but it has that additional interaction at the dopamine three receptors, which potentially could mean that it has maybe more of a procognitive effect, and maybe down in the row, potentially could be something involved in the reward processing and substance disorder. But again, that's theoretical at this point, and will will be kind of on the watch to see what kind of subgroup analyzes come out there.

Speaker 2  32:16
Well, I can sympathize with my patient now when they say, why the drug companies have to make the name so hard, because since I don't practice with these drug as much, I am even stumbling upon the name. So way to go. Dr. Schumann, thank you for that very informative podcast today.

Dr. Sean Kane  32:30
Thank you all very much. So with that, we'll go ahead and conclude, if you'd like, we'd love a five star review on iTunes. You can find us by searching for HelixTalk. We're also at HelixTalk.com where you can find our contact information, and you can also view some of our older episodes, if you don't want to do so in it. So with that, I'm Dr. King, I'm Dr

Unknown Speaker  32:48
shoeman, and I'm Dr. Patel, and as always, study hard.

Narrator - Dr. Abel  32:52
Thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science. For more information about the show, please visit us at HelixTalk.com you.