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00:00:06.639Hi Health Mart pharmacists from your education partner CEimpact, this is Game Changers.
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00:00:16.879I'm your host, Jen Moulton, and each week we have a conversation on a hot clinical topic that will keep you current in practice and position you as a resource for prescribers and patients.
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00:00:18.640Thanks for listening in.
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00:00:22.239Welcome to the Game Changers Clinical Update podcast.
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00:00:31.039I'm your host, Rachel Maynard, and today we're going to be talking about the role of atypical antipsychotics, also called second generation antipsychotics, in managing depression.
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00:00:42.000This is coming up because an atypical antipsychotic bubiteperone was recently approved as an add-on therapy along with antidepressants for the treatment of major depressive disorder in adults.
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00:00:52.399And it joins other atypicals, including aripifrazole, frespifazole, and type and extended release, as antipsychotics that are approved as adjunctive therapy for depression.
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00:01:04.560But this recent approval made a bit of a splash in headlines, and it raises questions about when lumatibrone should be considered as an add-on for depression, as well as when second generation antipsychotics fit in more broadly for depression.
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00:01:08.480So to help us dig into this topic, I'm very excited to introduce our guest today, Dr.
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00:01:09.359Sarah Grady.
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00:01:10.480So welcome, Sarah.
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00:01:12.719Morning, Rachel.
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00:01:13.439Thank you.
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00:01:15.120We're so happy to have you.
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00:01:19.280I know you've got a very busy schedule, so really appreciate you taking the time to chat with us today.
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00:01:29.120And for our listeners who haven't heard your voice on the podcast in the past and you've been on before, could you share a little bit about your background, your current role, and why you're interested in this topic?
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00:01:31.280Yes, thanks again.
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00:01:32.719My name is Sarah Grady.
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00:01:39.920I'm a professor of pharmacy practice at Drake University College of Pharmacy and Health Sciences.
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00:01:46.879I'm also a clinical pharmacist on the inpatient behavioral health unit at Broadlands Medical Center.
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00:01:59.120So I assist in the care of many patients that have depression, mild, moderate, severe, as well as difficult to treat depression.
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00:02:02.000So very interested in this topic.
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00:02:02.799Excellent.
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00:02:07.920Yes, it sounds like you'll have a lot of great practical experience to share with our listeners today.
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00:02:17.439So let's just start out by talking about Lumiteperone, which is this recently approved drug for as an adjunct to major depressive disorder.
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00:02:26.879So if we could just have an overview of what lumiteperone is and what it was previously approved for and how it works, that would be great, I think, to help level set us, get us on the same page.
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00:02:32.400Yeah, so lumiteperone has been out since approximately 2019.
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00:02:35.680It was originally FDA approved for schizophrenia.
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00:02:43.599Since then, it's achieved FDA approval, or I should say acquired FDA approval for bipolar one and two.
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00:02:53.280And most recently in November, as you stated, it received the adjunctive adjunctive agent for depression approval.
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00:03:00.960How it differs a little bit from the other second-generation antipsychotics with regards to its mechanism.
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00:03:03.520There are a few ways in which it differs.
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00:03:10.000The first way is that very strong 5-HT2A antagonist.
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00:03:17.919Obviously, the other antipsychotics have that mechanism as well, but this is very, very strong, quite strong.
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00:03:22.240It also has serotonin reuptake inhibition properties.
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00:03:32.560So this may give it some antidepressant effects that differ a little bit from the other second-generation antipsychotics.
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00:03:42.719Many second generation antipsychotics also have antidepressant properties, but none really have a great deal of serotonin reuptake inhibition.
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00:03:45.759So this is a difference in mechanism.
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00:03:49.199How will this translate clinically?
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00:03:54.960We obviously know it's got the FDA approval, but how will it work for the individual person?
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00:03:56.960It's going to probably work for some people.
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00:04:01.039It's not going to work for everybody, but we will see what happens.
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00:04:09.520I feel like in the management of depression, we need every single tool and agent and technique available.
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00:04:18.319So this just adds to our tools, and it might be appropriate for some people, but it may not be appropriate for everybody.
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00:04:24.160I think you've highlighted a really important point that will come up probably again multiple times in our discussion.
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00:04:35.519But thank you for the summary and also for sort of tying in how the mechanism may potentially theoretically have benefit for depression to that serotonin, how did you describe it?
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00:04:37.439Serotonin and serotonergic.
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00:04:40.000Yeah, serotonin reuptake inhibition.
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00:04:40.800Right.
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00:04:45.279So again, as we think about our SSRIs, similar sort of potential benefit there.
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00:04:59.199Again, strictly through mechanism of action, how that will play out clinically may yet be seen, but that actually transitions nicely into this new approval for limoteperone in the as an adjunct for depression.
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00:05:07.600And so maybe you can talk a little bit about some of the clinical studies that were used to get that approval and how what what kinds of data we have so far.
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00:05:20.639Yeah, so the clinical trials again showed some very some good results looking at the uh primary outcome measures, a reduction on the madras.
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00:05:31.439The madras is the kind of one of the gold standards that we use for scoring depression, and it did show improvement compared to placebo.
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00:05:42.959And the the trial was set up in a similar fashion to some of the other second-generation antipsychotics that currently have FDA approval.
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00:05:46.480So, again, some good measures that they looked at.
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00:05:53.439They had rather strict inclusion-exclusion criteria, which is typical for a trial such as this one.
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00:06:01.759So, again, the the trials look beneficial, but we will have to see how this works out clinically in practice.
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00:06:02.319Yeah.
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00:06:09.920Okay, I'm glad you reiterated that because as you say, real-world data can sometimes look different than these trials, which are often very short.
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00:06:13.519I think these were no more than a few weeks of duration.
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00:06:18.000So how that will play out longer term is always sort of yet to be seen.
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00:06:27.360And you mentioned it was studied versus placebo, but just to be clear, versus placebo, but in patients already on antidepressants, is that correct?
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00:06:28.160Correct.
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00:06:31.120They were already on, because this is an adjunctive trial.
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00:06:35.360So they were already on antidepressant therapy.
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00:06:49.839And as you mentioned, these are acute trials, you know, so six, four, six, eight weeks in duration, and also a couple hundred patients in each uh treatment group.
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00:06:57.279So I think it's important to keep that in mind because that's why we'll need to see how this plays out clinically.
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00:06:58.480Right, absolutely.
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00:07:00.079Okay, great summary there.
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00:07:03.199So we've got that foundation with lumiteperone.
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00:07:18.319Let's talk about second generations, second generation antipsychotics more broadly and their role as adjunctive therapy for depression, because not everyone with depression needs a second generation antipsychotic.
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00:07:26.800So, what what really is the broader role outside of lumiteperone specifically for these second-generation antipsychotics in managing depression?
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00:07:28.399Absolutely.
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00:07:37.600They are geared mainly toward individuals that have a partial response to a traditional antidepressant.
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00:07:41.360Okay, and so I can define what a response is.
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00:07:45.360A response is a 50% reduction in baseline symptoms.
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00:07:52.560A partial response would be a 25 to 49.99% reduction in symptoms.
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00:07:58.959Okay, so these are really geared towards people that have that partial response mainly.
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00:08:02.399This is what they are geared towards.
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00:08:09.279And again, the evidence is there that they can be helpful for that partial response.
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00:08:16.000But I want to make it clear that there are also other options that can be helpful for a partial response.
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00:08:23.519And clinical practice guidelines highlight these options available for partial response.
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00:08:33.440Obviously, they include the second generation antipsychotics, but you can also consider psychotherapy if you're not already doing that.
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00:08:38.399And there are other agents that have been studied for partial response.
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00:08:45.279There, they may not be necessarily listed high-ranking and treatment guidelines, but we can look at them.
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00:08:54.480These include agents such as lithium, abuse pyrone, you know, we have thyroid hormone supplementation.
00:08:54.480 -->
00:09:01.279So there are lots of ways that you can manage partial response according to treatment guidelines.
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00:09:15.120Another thing you can do first and foremost is we want to, and we can do this as pharmacists, we want to see are they taking, you know, whenever a patient tells me my antidepressant isn't working, I ask them kind of the obvious questions.
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00:09:17.200Are you trying to take it every day?
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00:09:19.039Is your dose high enough?
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00:09:21.360Um, has your duration been long enough?
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00:09:23.120All those things matter.
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00:09:32.639And especially if somebody thinks the antidepressant, the traditional antidepressant, might be helping them, we might want to look at increasing the dose.
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00:09:36.799And, you know, we want to stay within the FDA recommended range.
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00:09:44.799But, you know, for example, if they're taking Sertuline, 100 milligrams, and they're seeing a little bit, they're seeing a pressure response, they're feeling a little bit better.
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00:09:56.960Maybe we can see if they can tolerate a higher dose, you know, and so maybe look at dose optimization, um, considering all our options for pressure response.
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00:10:06.639Obviously, that includes our um, you know, our second generation antipsychotics, but we have other medications that we can look at too.
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00:10:08.799You called up too many important things.
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00:10:09.919Yeah, go ahead.
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00:10:10.480Sorry.
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00:10:11.679My apologies.
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00:10:14.080We just the point is we have a lot of options.
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00:10:29.360And yes, second generation antipsychotics, they have the FDA approval, and we want to consider them, but we have lots of other routes we can go if somebody doesn't feel comfortable starting one of them for whatever reason, you know.
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00:10:32.159So lots of options available, which is a good thing.
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00:10:33.360Yeah, absolutely.
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00:10:39.360And and like you alluded to with the approval of lumiteprone, it is another tool in the toolbox.
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00:10:52.879And I think that that also resonates here, where we have lots of tools in the toolbox more broadly in terms of how how patients can be managed, not necessarily going to a second gender recent antipsychotic or even this specific drug per se.
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00:10:55.279So, but yeah, you brought up so many important points there.
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00:10:57.200I just want to reiterate a few of them.
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00:11:00.799The idea of partial response and evaluating that.
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00:11:11.519And one thing that comes to mind is the idea of giving the anti traditional antidepressant, as you said, at the optimized dose for enough time.
00:11:11.519 -->
00:11:16.879So what as you said, that's a really important part for pharmacists to be looking for.
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00:11:19.679So um what is the dose?
00:11:19.679 -->
00:11:20.799Is it optimized?
00:11:20.799 -->
00:11:21.840And then how long?
00:11:21.840 -->
00:11:23.840Because it takes time to titrate too.
00:11:23.840 -->
00:11:26.240And so how do you consider all of that?
00:11:26.240 -->
00:11:35.200If a patient is starting out on an antidepressant, a traditional antidepressant, how do you ensure what what kind of time frame are you waiting for them to get to that optimized dose?
00:11:35.200 -->
00:11:40.799And then how long should they expect it to take for the antidepressant to kick in at the optimized dose?
00:11:40.799 -->
00:11:43.600What is what is that sort of time frame that you're looking for generally?
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00:11:47.440Yeah, it's a it's a on average, it's it's lengthy.
00:11:47.679 -->
00:11:48.000Yeah.
00:11:48.159 -->
00:11:51.679And that is difficult for for everybody.
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00:12:06.080It's, you know, when when when you know folks have depression, not feeling well, wanted to feel better yesterday, they can really take these medications, um, you know, several weeks really.
00:12:06.080 -->
00:12:18.720Um, most of our medical literature states that it can take, you know, uh a full six to eight weeks or longer to see full therapeutic benefit.
00:12:18.720 -->
00:12:34.080And it has again, we need to we need to factor in titration, um, you know, and so yes, like I said, really six to eight weeks or longer to to see a therapeutic benefit.
00:12:34.080 -->
00:12:35.519Um, that's an average.
00:12:35.519 -->
00:12:40.159It will there will be some individual variation, like there always is.
00:12:40.159 -->
00:12:48.879And that's another reason why it makes you know mental health management a bit challenging, you know, from time to time.
00:12:48.879 -->
00:12:58.879But again, pharmacists were perfectly uh positioned to kind of reiterate these concepts along with adherence, taking the medication every single day.
00:12:58.879 -->
00:13:10.399I think the other thing that kind of compounds traditional antidepressant treatment is that on average, different symptoms will start to improve at different times.
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00:13:24.159So we we always like to say that the physical symptoms of depression, sleep disturbances, appetite disturbances, low energy, those symptoms may start to improve before the emotional symptoms of depression.
00:13:24.159 -->
00:13:34.320You know, the emotional symptoms, depression, the sad mood, the loss of interest and activities one normally finds enjoyable, the suicidal ideation, you know.
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00:13:40.240So physical symptoms of depression may start to improve before emotional symptoms of depression.
00:13:40.240 -->
00:13:52.080And, you know, that's one of the reasons why we have, you know, the black box warning, because particularly in younger people, this can happen to anybody, but energy may improve before the emotional symptoms.
00:13:52.080 -->
00:13:53.759And so this can be problematic.
00:13:53.759 -->
00:13:59.440So we have lots of factors, I guess, going on with traditional antidepressants.
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00:14:12.960But yes, really, if you look at the the trials among the antidepressants, the traditional antidepressants, you know, those are six-week trials, typically eight-week trials, and and there's a reason for that.
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00:14:13.840Yeah, yeah.
00:14:13.840 -->
00:14:22.000I think that's uh such an important point to drive home because as you said, pharmacists educating about this, helping patients have realistic expectations when they're starting.
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00:14:39.120So I think it's great you called out physical symptoms result or improving before emotional symptoms, but just the length of time this can take generally and supporting them through that titration and with adherence, as you said, even if you're not feeling full benefit, continue on to see if you're going to get that response.
00:14:39.120 -->
00:14:49.120So you mentioned anti-psychotic the antipsychotics as an adjunct for patients with partial remission or partial response, I should say.
00:14:49.120 -->
00:14:58.799When would you think about switching to a different traditional antidepressant versus then adding the antipsychotic or another adjunct?
00:14:58.799 -->
00:15:01.600But what do you think about switching versus adding?
00:15:01.600 -->
00:15:03.360Yeah, great question.
00:15:03.519 -->
00:15:05.679I can think of a couple scenarios.
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00:15:19.200Number number one being, so I talked previously about response, you know, 50% reduction from baseline symptoms, pressure response 25 to 49.99% reduction in symptoms.
00:15:19.200 -->
00:15:24.240Non-response is considered less than 25% reduction in symptoms.
00:15:24.240 -->
00:15:33.120So certainly when somebody has non-response to an agent, and again, we have to factor in are they taking it every day as prescribed?
00:15:33.120 -->
00:15:34.559Is the dose high enough?
00:15:34.559 -->
00:15:36.080Is the duration long enough?
00:15:36.080 -->
00:15:38.559So we have to factor in those three.
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00:15:43.360Also, if they're having side effects that are bothersome to them.
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00:16:08.480I think in a lot of cases, depends on the person, but you know, some people uh uh understandably feel so terrible with the sad mood and the other symptoms of depression that they may be willing to tolerate maybe some dry mouth or you know, maybe some of the other the stomach upset, some of the other um antidepressant side effects that are commonly seen.
00:16:08.480 -->
00:16:23.440But you know, let's say they develop a side effect that it's just too bothersome to them and it makes them feel even worse, you know, than they already do, then you know, that would be another scenario where we wouldn't want people to be on the drug.
00:16:24.080 -->
00:16:24.399Okay.
00:16:24.399 -->
00:16:41.519And when thinking about antipsychotics specifically in the menu of other options that you have as an adjunct and considering some of the pros and cons with antipsychotics broadly, how does that factor into your decision-making process with the patient?
00:16:41.519 -->
00:16:44.559Yeah, uh front of mine.
00:16:44.960 -->
00:16:54.159I feel as though there is always, I don't want to say always, but there is usually a risk versus benefit discussion.
00:16:54.159 -->
00:17:02.240So we know the benefit of some of these second generation antipsychotics that have FDA approval for this.
00:17:02.240 -->
00:17:04.240The data is out there.
00:17:04.240 -->
00:17:08.400Data is out there, so we we know the benefits.
00:17:08.400 -->
00:17:20.000Um, what we need to discuss, especially as pharmacists, are the risks and mainly the risks of long-term use of second-generation antipsychotics.
00:17:20.000 -->
00:17:31.599So we need to be talking with patients about the risk of what I call or what we call drug-induced movement disorders, uh, formally known as EPS.
00:17:31.599 -->
00:17:41.839Okay, so risk of tartar dyskinesia, although the risk of TD is low with the second generation antipsychotics, it's not zero.
00:17:41.839 -->
00:17:51.599So whenever I am speaking to or with a patient about an antipsychotic, I don't care what it is, I don't care what the purpose is.
00:17:51.599 -->
00:17:54.079Take apiprazole, for example.
00:17:54.079 -->
00:18:00.319I would say in my setting, its most common use is an adjunctive agent for depression.
00:18:00.319 -->
00:18:06.480So we have many patients that are on aeropirazole for that purpose and they're on low doses.
00:18:06.480 -->
00:18:12.480Um, and I'm always letting them know about the risk of taryskinesia with long-term use.
00:18:12.480 -->
00:18:15.359Low risk, very low risk, but not zero risk.
00:18:15.359 -->
00:18:20.480And again, pharmacists in any setting can certainly talk to patients about that.
00:18:20.480 -->
00:18:22.559Metabolic risks.
00:18:22.559 -->
00:18:37.279Um, so the agents, most of the agents, with the exception of quatiapine, most of these agents are gonna have a lower risk of weight gain and hyperglycemia and dyslipidemia, but again, may not be zero.
00:18:37.279 -->
00:18:43.680So I'm always encouraging patients that are taking an antipsychotic and they're gonna be using it long term.
00:18:43.680 -->
00:18:45.759We want to be monitoring that.
00:18:45.759 -->
00:18:53.519And some of these agents, certainly not all of them, you know, we can sometimes have some increased prolactin levels.
00:18:53.519 -->
00:19:02.160Again, this is going to be less of a factor with the second generation antipsychotics that we have FDA approval for for this purpose.
00:19:02.160 -->
00:19:27.759But like I said, I I really think that pharmacists in every single setting that, you know, if we're if we're taking care of folks that are taking um antipsychotics for any purpose, we do want to let them know about an ongoing conversations about the risk of uh drug-induced movement disorders, metabolic side effects, and depending on the antipsychotic, the risk of hyperprolactinemia.
00:19:29.279 -->
00:19:29.839Absolutely.
00:19:29.839 -->
00:19:45.599Those are definitely important safety considerations to be educating patients about, and also again, thinking about those in the risk-benefit analysis when you're considering what options are available for patients who've had partial response.
00:19:45.599 -->
00:20:01.279So considering all those, does that do atypical second generation antipsychotics still provide a where do they sort of rank in terms of the options where you might think about next steps for a patient with a partial response to a traditional antidepressant?
00:20:01.279 -->
00:20:02.880How does it sort of stack up?
00:20:03.119 -->
00:20:04.640Yeah, great question again.
00:20:04.640 -->
00:20:08.079This is where I like to look at our treatment guidelines.
00:20:08.079 -->
00:20:23.599And in the last couple of years, the the more recent treatment guidelines have definitely put second generation antipsychotics in the conversation for looking at them as an adjunctive agent.
00:20:23.599 -->
00:20:31.599But I want to underscore they're not the only agents that have been moved up in the algorithm, if you will.
00:20:31.599 -->
00:20:38.640Um, another option that has moved up in treatment guidelines is psychotherapy.
00:20:38.640 -->
00:20:45.519You know, so again, I want to underscore, yes, they are they are an option.
00:20:45.519 -->
00:20:49.599They are a good option for some people, not everybody.
00:20:49.599 -->
00:21:08.559You know, I always I feel like in my practice settings, uh, particularly I'll I'll use Arab Hippers as an example, just because we are at this time at my institution it using it the most out of the other FDA-approved agents, uh, probably because it's had this indication the longest, right?
00:21:08.559 -->
00:21:13.440And we're familiar with it, but we are really watching to see if it works or not.
00:21:13.440 -->
00:21:18.000We are really watching to see if the patient is comfortable with it.
00:21:18.000 -->
00:21:21.359Many of our patients are, but not all of them.
00:21:21.359 -->
00:21:29.200You know, in the case of uh Airpipperzole, we we see a lot of side effects of acadesia, feeling restless.
00:21:29.200 -->
00:21:38.799And particularly when we have someone that has depression, they have loss of interest, suicidal thoughts, we don't want them feeling restless.
00:21:38.799 -->
00:21:46.400So we are very intentional and deliberate in watching, you know, is it working for the patient?
00:21:46.400 -->
00:21:49.839And if it's not working, we transition them off of it.
00:21:49.839 -->
00:21:52.640The again, that risk versus benefit.
00:21:53.839 -->
00:21:59.759Yeah, and shared clinical decision making, having those conversations up front with a patient, helping them wait through the options and then.
00:21:59.759 -->
00:22:05.440As the patient is starting and continuing tolerability, evaluating, reevaluating.
00:22:05.440 -->
00:22:07.839So, all part of that standard patient care process.
00:22:07.839 -->
00:22:09.200I love that you called that out.
00:22:09.200 -->
00:22:21.519I think what you have been highlighting in your practice is a great opportunity to sort of segue into the role of Luma Taperon, since that was our hook for this discussion and why we're sort of talking about this more broadly.
00:22:21.519 -->
00:22:28.559Where do you think it's going to fit in compared to other second generation psychotics in this role as adjunct therapy for depression?
00:22:28.559 -->
00:22:31.039How does how does it sort of compare or stack up?
00:22:31.039 -->
00:22:32.079Sure.
00:22:32.240 -->
00:22:32.640Yeah.
00:22:32.640 -->
00:22:35.440And I'm still, it's a newer agent, right?
00:22:35.440 -->
00:22:44.480So I'm like everyone else, I'm still learning about it and I'm still thinking about how it fits in or what differentiates it more importantly.
00:22:44.480 -->
00:22:52.799Again, the first thing that comes to mind is it does seem to have a different mechanism than the others.
00:22:52.799 -->
00:22:58.960And again, so that might play a role, I guess, in in two regards.
00:22:58.960 -->
00:23:08.480One could be yes, it for some people, it may really provide that additional antidepressant property, which is what we're looking for.
00:23:08.480 -->
00:23:21.039But the other thing, Rachel, that I've been thinking about, because this is where my trained as a pharmacist, I'm always thinking actually safety first because it has serotonin reuptake and ambition.
00:23:21.039 -->
00:23:21.920Yeah.
00:23:21.920 -->
00:23:28.880Will that put us at greater risk for serotonin syndrome with some of our SSRIs and SNRIs?
00:23:28.880 -->
00:23:34.480And I noticed that, you know, that is mentioned in the medical literature a little bit.
00:23:34.480 -->
00:23:38.000The clinical trials didn't pick that up.
00:23:38.000 -->
00:23:40.720But again, they were short duration, right?
00:23:40.720 -->
00:23:45.200Um, you know, and hundreds of patients, you know, versus thousands.
00:23:45.200 -->
00:23:52.880So I feel like pharmacists, especially, in fact, you know, I had a physician call me a couple weeks ago.
00:23:52.880 -->
00:23:57.599You know, they saw the new indication and they said, We, you know, what do you what do you think?
00:23:57.599 -->
00:23:59.599I read the trials, just like you did.
00:23:59.599 -->
00:24:01.519Yes, it can be helpful.
00:24:01.519 -->
00:24:03.599Stats look decent.
00:24:03.599 -->
00:24:12.799Yes, we're we gotta factor in not a long duration, a couple of hundreds, a couple hundred patients versus a couple thousands.
00:24:12.799 -->
00:24:14.319We got to factor all that in.
00:24:14.319 -->
00:24:19.759And I said, I said, yeah, you know, on paper, it it looks good and obviously has FDA approval.
00:24:19.759 -->
00:24:24.400But what I don't know about is will we have a risk of serotonin syndrome?
00:24:24.400 -->
00:24:25.279I don't know.
00:24:25.279 -->
00:24:29.440I don't know, you know, but I I put that, I just mentioned that to the physician.
00:24:29.440 -->
00:24:34.720They're like, yeah, yeah, I gotta monitor for that, and let's let the let's let the patient know about that.
00:24:34.720 -->
00:24:35.039Yeah.
00:24:35.039 -->
00:24:42.240So that's probably you know a safety mechanism for for we as pharmacists to think about.
00:24:42.240 -->
00:24:51.759The other thing that we've been seeing, so we have been using, you know, the the the new agent, newer agent for this indication.
00:24:51.759 -->
00:24:54.720We have been using it at our practice, but not for this purpose.
00:24:54.720 -->
00:24:58.720We've been using it for schizophrenia, we've been using it for bipolar.
00:24:58.720 -->
00:25:06.640We are seeing varies per person, but we are seeing from a side effect profile some you know, some sedation.
00:25:06.640 -->
00:25:09.920Um so we've been using it at bedtime.
00:25:09.920 -->
00:25:17.680So this may um factor in to folks that they have the type of depression where they just can't sleep, right?
00:25:17.680 -->
00:25:19.039They can't sleep well.
00:25:19.039 -->
00:25:25.839Even the maybe the traditional antidepressant has helped the insomnia a little bit, but they're still not sleeping well.
00:25:25.839 -->
00:25:33.119So maybe laminateporone would um you know provide some additional sedation for them.
00:25:33.119 -->
00:25:41.920So sedation we are seeing, we're seeing some dry mouth, we're seeing some nausea again, and I think uh the nausea is probably from the serotonin reuptake and ambition.
00:25:41.920 -->
00:25:44.799So, you know, those are just some things to factor in.
00:25:44.799 -->
00:26:02.880So to summarize, we'll see how it plays out, but just on paper, it looks like the mechanism might be may add something to what's already out there from both an effectiveness standpoint as well as a safety standpoint.
00:26:02.880 -->
00:26:08.559Again, I'm I'm hoping for the effectiveness standpoint, and certainly that's what we've seen in the clinical trials.
00:26:08.559 -->
00:26:17.279But we've talked about the potential limitations of our trials, and as pharmacists, we will be conducting further post-marketing surveillance.
00:26:17.839 -->
00:26:18.160Sure.
00:26:18.160 -->
00:26:26.319That's a great summary, and I that ties into a lot of the counseling points we'd want to be thinking about with patients starting this too.
00:26:26.319 -->
00:26:43.039And I love how you brought together that serotonergic effect could be providing some benefit in this specific indication, but also could be introducing some risk in this indication because these patients are also going to be on traditional antidepressants, often, which have serotonergic effects.
00:26:43.039 -->
00:26:45.839And so, yeah, that's a very good consideration.
00:26:45.839 -->
00:27:06.160And then when you think about serotonergic considerations and other meds that can then add to that burden and sort of tip a patient over potentially, having that on your radar is really important because I don't know that I would necessarily think of a second generation antipsychotic as having a serotonin, you know, potentially contributing to that to that burden.
00:27:06.160 -->
00:27:08.400So really important point to call out there.
00:27:08.400 -->
00:27:11.599And the sedation also is an interesting consideration.
00:27:11.599 -->
00:27:16.799As you said, if a patient's struggling with insomnia, this may have potential benefit there for some patients.
00:27:16.799 -->
00:27:18.559As you said, it's so patient-specific, right?
00:27:18.559 -->
00:27:23.599And we really need to think about the individual patient and what's going to be beneficial or not for them.
00:27:23.599 -->
00:27:25.599But yeah, it's yeah.
00:27:26.000 -->
00:27:33.359And Rachel, I bring that distinction up just because, again, we are most familiar at my setting with aeriprizole.
00:27:33.359 -->
00:27:33.920Right, yeah.
00:27:33.920 -->
00:27:45.839And aripazole, it varies per person, but aeropiprazole, especially at the lower doses that we use for depression adjunct, it can activate people, it can energize people.
00:27:45.839 -->
00:27:46.400Right.
00:27:46.400 -->
00:27:48.880So we usually give it in the morning.
00:27:48.880 -->
00:27:56.079Yes, there's always a few people, it makes tired, but that, you know, that is a kind of a differentiating factor, I think.
00:27:56.079 -->
00:28:00.640And and earlier in the podcast, we talked about, you know, cotiopine.
00:28:00.640 -->
00:28:21.200Obviously, cotiopine can be sedating, but I think it's good to have a mixture of things that can maybe add to some energy or maybe help with sleep symptom-wise, because the sleep can can be an issue, whether it's insomnia or hypersomnia.
00:28:22.799 -->
00:28:37.759So, in terms of any other practical or practical considerations or counseling points that you want people to know about with lumitoporon, the other thing that's coming to my mind is cost because Eric Piperzole, as you said, has been around for years, has had that indication for years, is generic.
00:28:37.759 -->
00:28:39.279This is not going to be a generic.
00:28:39.279 -->
00:28:46.720Any other considerations that our listeners should be aware of when thinking about this sort of new introduction into this indication?
00:28:48.160 -->
00:28:55.359I'm thinking, and yeah, thank you, of course, for mentioning the cost factor, because we have to factor that into the risk versus benefit.
00:28:55.359 -->
00:29:10.000But um, but yeah, again, the the difference in mechanism, I think pharmacists want to highlight, which can be a positive thing, which we saw in the studies, um, but again, may contribute to that serotonin burden.
00:29:10.000 -->
00:29:11.839So we want to probably think about that.
00:29:11.839 -->
00:29:27.680And of course, the mentioning the long-term potential adverse effects with antipsychotics in general, the drug-induced movement disorders, especially tardivyskinesia, metabolic risk, and risk of hyperprolactinemia with some of the agents.
00:29:28.799 -->
00:29:33.279Good counseling points to keep in mind with the second generation antipsychotics in general.
00:29:33.279 -->
00:29:38.000We talked about the sort of onset effect for traditional antidepressants.
00:29:38.000 -->
00:29:45.279How long would you tell a patient to expect to see onset of effect for an adjunct antipsychotic in general?
00:29:46.400 -->
00:29:48.480Yes, excellent question.
00:29:48.480 -->
00:29:59.680And we expect to start to see some improvement in, I guess, those residual symptoms of depression really by by two weeks.
00:29:59.680 -->
00:30:01.359We should start to see something.
00:30:01.359 -->
00:30:08.880Um, not full benefit, but we should see improvement in something by two weeks.
00:30:08.880 -->
00:30:20.640Um, depending on the agent when used for this purpose, they we might start to see some earlier results compared to traditional antidepressants.
00:30:20.640 -->
00:30:26.559I would say certainly at one month out, we would want to see improvement.
00:30:26.559 -->
00:30:33.440And if we're not seeing improvement, then we're going to have conversations about do we leave this on a little bit longer?
00:30:33.440 -->
00:30:35.680If so, how much longer?
00:30:35.680 -->
00:30:39.839Um, because again, risk versus benefit.
00:30:39.839 -->
00:30:45.519I always, this is just my personal opinion, and I always share this with patients.
00:30:45.519 -->
00:31:01.680It is my personal opinion, but if you know, with the potential long-term side effects of antipsychotics, if they are not helpful, we don't want to be taking them, and we want to look at other options for um augmentation.
00:31:01.680 -->
00:31:22.079And as we stated throughout the podcast, we have other options that can be helpful, optimizing the dose, switching the antidepressant, adding on therapy, adding on, you know, you know, and even we didn't speak about this, but you know, even maybe adding on another antidepressant to a traditional antidepressant.
00:31:22.079 -->
00:31:23.200There's data for that.
00:31:23.200 -->
00:31:31.039So, yes, and again, this is this is where pharmacists in any setting can be uh instrumental, you know.
00:31:31.039 -->
00:31:48.160Let's say there's someone coming to your pharmacy to pick it up their second month of their second generation antipsychotic for their depression augmentation, particularly if you know that patient well, you know, we would start to we expect to see some benefit by now.
00:31:48.160 -->
00:31:50.160We expect to see something.
00:31:50.160 -->
00:32:00.160Um again, we want to verify adherence because maybe they're showing up at your pharmacy five or six weeks after they're starting it.
00:32:00.160 -->
00:32:05.279And if they're not taking it every day as prescribed, it it's not gonna work.
00:32:05.279 -->
00:32:08.799Uh, we're not gonna get the best effectiveness from the medication.
00:32:09.119 -->
00:32:09.599Right.
00:32:09.599 -->
00:32:21.680Well, I love how you're reiterating the point out of adherence and the crucial role for pharmacists because often we do have visibility into when that refill is coming up, and that is right about the time frame when we would be hoping to see response.
00:32:21.680 -->
00:32:30.160So good, great time to check in, have that conversation around tolerability, but also efficacy and and how the patient's doing overall, and then reevaluating.
00:32:30.160 -->
00:32:34.160Because as you said, this doesn't have to be this isn't our only option.
00:32:34.160 -->
00:32:35.359We have lots of options.
00:32:35.359 -->
00:32:37.839So I think that's a great point to tie that all together.
00:32:37.839 -->
00:32:47.599And I thank you for also speaking to how long we expect to see that benefit because I think that's a consideration that we should be thinking about when we're seeing those patients at the check-in.
00:32:47.599 -->
00:32:49.920So we're about out of time for today.
00:32:49.920 -->
00:32:56.240So it is our game changers podcast, and we do want to wrap up with a game changer and what you want our listeners to walk away with today.
00:32:56.240 -->
00:32:58.640So, what would you say is the game changer, Sarah?
00:32:59.599 -->
00:33:16.559I'd say the biggest game changer is we have another tool in our toolbox in in our our fight against this condition that impacts many people all over the world.
00:33:16.559 -->
00:33:22.880Um, it may impact us, it may impact our family, our friends, our colleagues.
00:33:22.880 -->
00:33:29.519So, yes, like anything else, it's not a perfect option, but it's another option.
00:33:29.519 -->
00:33:35.119And it's an option that can maybe help some of our patients.
00:33:35.119 -->
00:33:36.799It's not going to help all our patients.
00:33:36.799 -->
00:33:44.720It's not the right option for all our patients, but a game changer is we have another option in our toolbox.
00:33:45.359 -->
00:33:46.480Excellent summary.
00:33:46.480 -->
00:33:53.839Another tool in the toolbox is a great takeaway, and also waiting and seeing how it pans out in the real world.
00:33:53.839 -->
00:33:57.440We'll we'll have to wait and see and maybe check back in a couple of years.
00:33:57.440 -->
00:34:00.000Yes, we're gonna cross our fingers.
00:34:00.000 -->
00:34:00.880That's right.
00:34:00.880 -->
00:34:01.440That's right.
00:34:01.440 -->
00:34:02.079Excellent.
00:34:02.079 -->
00:34:03.680Well, thank you so so much, Sarah.
00:34:03.680 -->
00:34:06.079Really appreciate your time and your expertise on this topic.
00:34:06.079 -->
00:34:07.599Thank you, Rachel.
00:34:07.599 -->
00:34:08.639You have a good day.
00:34:08.880 -->
00:34:09.760Thank you.
00:34:09.760 -->
00:34:12.159And that's it for this week.
00:34:12.159 -->
00:34:16.480Be sure to log in to Healthmart University to claim your CE credit for this episode.
00:34:16.480 -->
00:34:18.880As always, have a great week and keep learning.
00:34:18.880 -->
00:34:20.079We'll talk to you next week.
