PsychCase360: Choosing the Right Long-Acting Injectable for Patients With Schizophrenia

TRANSCRIPT

Melissa Vitale (0:05)

Welcome to PsychCase 360.

Roueen Rafeyan (0:17)

We’re happy you’ve joined us. We’re going to review two cases for you showing the challenges and effective treatments in schizophrenia. I’m Dr. Ruin Rafian, Clinical Assistant Professor of Psychiatry at Northwestern University Feinberg School of Medicine. I’m delighted to be joined by my colleague, Melissa Vitale, from Research Psychiatry.

Case 1: José

Melissa Vitale (0:39)

Here is the first patient example that we’re going to walk through. His name is José. He’s a 29-year-old grocery store clerk living with schizophrenia for about five years now.

He’s been seen at our clinic since referral from his primary care provider five years ago. He’s struggled a lot with adherence to oral medications since he’s been diagnosed, which we see a lot of struggles with oral adherence.

Roueen Rafeyan (1:07)

That is so common, actually, starting with this history. I think for those of us who treat schizophrenia, we see this on a daily basis. One of the challenges with this disorder is adhering to medication, and by the way, medication compliance, or what I usually like to refer to as partial compliance, is not unique to schizophrenia.

We see this with all diseases states, that it’s just human nature. It’s difficult to adhere to strict medication regimen.

Managing Relapse and Medication Adherence

Melissa Vitale (1:40)

And remember to take your meds if you’re traveling or whatnot. So José here, he’s experienced multiple relapses over the last few years due to a lot of these missed doses of medication, his oral medication, leading to repeated hospitalizations, which have then disrupted his work and family life due to his relapses.

Roueen Rafeyan (2:02)

Melissa, I think we are just being very general when talking about disruption to work and social life. But with each relapse, and you’ve had that experience as well, it’s more than that. The impact of a relapse on the patient goes way beyond that.

Melissa Vitale (2:19)

Right, right. So despite understanding the importance of taking his meds, he’s had difficulty maintaining the daily regimen, especially periods where his symptoms worsen, right? It’s almost like a revolving door, downhill-type process when he stops taking his meds and then starts to relapse.

José and his care team have decided that a long-acting injectable would be a good option for him as it would increase the adherence and lower the risk of subsequent relapses or delay those times to those relapses. So really, when we’re talking to our patients about a long-acting injection, it’s always good to use positive interviewing, right? Ask the patient what their goals are.

Are their goals to maintain his job as a store clerk or maintain those social relationships with his parents? Or maybe he has a girlfriend, right? So we’re going to use that when talking to him about, you know, how beneficial an LAI might be for him.

Roueen Rafeyan (3:22)

And, you know, while you’re just touching upon some of the challenges, there are a couple here that I would like to share with our audience as clinicians. We tend not to think about long-actings earlier in the course of the treatment. We wait until a patient like José has multiple hospitalizations before thinking maybe a long-acting is a good choice in his treatment.

However, again, we talked about it earlier, each relapse patients lose. There’s a lot to lose with each relapse. Disease gets more difficult to treat, potentially may even end up treatment resistance.

When we have effective ways of delivering a medication, it should be considered early on in the treatment. And then many times patients will push back. Again, let’s be real.

They have concerns about getting an injection. At that point, we have to implement a lot of motivational interviewing, getting them to collaborate with us to accept an injectable.

Transitioning to Long-Acting Injectables

Melissa Vitale (4:30)

Yes. Yes. And we also want to remind them that LAIs aren’t only for a last resort, right?

So and make sure that they understand it’s not the same as that immediate acting injection that they might have received in an inpatient setting or so on. So in this case, José has accepted to take a form of a long-acting injection and he switched from his oral risperidone to risperidone subcutaneous, a once-monthly injection.

Roueen Rafeyan (5:02)

In this case, it makes sense. He is on risperidone. The treatment team has established that he responds to this compound, tolerates it fairly well.

So a good move trying to switch him to an injectable form of oral risperidone.

Melissa Vitale (5:19)

Yes. Yes. So José comes in at his next appointment and he reports to us some injection site pain and itching.

And so we decide to then switch him to paliperidone palmitate once monthly. So we’re going to refer to this as PPOM in the future when talking about paliperidone once monthly.

Roueen Rafeyan (5:40)

Yeah, that’s a good example of good decision on initial injection as a long-acting, it’s the same compound. However, for reasons that the patient is expressing, it’s not comfortable getting a subcutaneous injection. Otherwise, the injection choice was good, could have really helped him in the long term.

Now we have to look at another compound that is close or same as risperidone, but it is not subcutaneous. So it does, again, make sense that treatment team decided to go with paliperidone palmitate once monthly.

Melissa Vitale (6:13)

So he completes the two loading doses with ease and he doesn’t experience any injection site pain or itching. And then we schedule him for his next injection 30 days later. So José then, as time goes on, he continues to struggle with keeping his appointments as we see quite often with our patients and follow-ups.

And he misses his scheduled appointment and comes to the clinic six weeks following his last injection. At that time, we noticed some breakthrough symptoms, including paranoia and hallucinations. And we’ve also noticed some poor hygiene and so on.

So at that point, he is tolerating the injections well, he’s not having any injection site pain. The medication does work for him when he is adherent to the plan and timing.

Roueen Rafeyan (7:10)

You know, what you just covered so far, it’s such a common problem. Many of the injections that are monthly, every four weeks, again, our patients with the schizophrenia struggle with keeping appointments, coming on time, very common. They will walk in six weeks, seven weeks later, and then that leaves us in a difficult spot because what do we do?

Do we start all over again? So it is a common problem in clinical practice.

Melissa Vitale (7:36)

Yes, yes. And the current dose of 156 milligrams had been doing well, controlling his symptoms, but efficacy had then waned.

Roueen Rafeyan (7:45)

Since it was supposed to come in at four weeks, it shows up at six weeks, well, medication levels do drop and is showing breakthrough symptoms. Yes. Now, at this point, the question is, what do we do?

Do we increase the psychosocial interventions? Talk to the case managers, to parents, or if there’s anyone involved in his care to make sure that he comes in every four weeks, because we need to make sure he gets the medication every four weeks. Because again, paliperidone palmitate comes in a three-month and a six-month version.

So if we are thinking that he is a good candidate for that, but we still need to have him on paliperidone palmitate monthly for four months. So that’s when we really have to get all the help we can to make sure he makes it.

Melissa Vitale (8:33)

And I think it’s also important to let him know about those three and six-month options. So it’s something that he can work towards and set a goal to get to. So that’s when we would have that conversation with him of the need to maintain those appointments monthly for the next two to three months, so that we can have him on a steady dose and get him to a steady state on the paliperidone palmitate and ensure efficacy at that time.

Roueen Rafeyan (9:00)

Now, so you brought up a great point. To discuss with him early on that, look, we are considering this medication for you. For the first four months, it’s going to be once a month.

However, once we establish that you’re doing okay on it, you’re tolerating it okay, and it’s controlling your symptoms adequately, then you have two options, to every three months or once every six months. And that becomes a very, a point that many patients will understand and become more invested in their treatment, because it’s much easier to get an injection once every three months or once every six months.

Melissa Vitale (9:37)

Two times a year.

Roueen Rafeyan (9:39)

Yeah, so.

Melissa Vitale (9:40)

Yes. And we also have to remind the patient that just because they’re only on the once every three month or once every six month dosing schedule, we can still bring them into the office and see them and focus on other aspects of their life, like their social life, their work, maybe how their medical care has been going.

Roueen Rafeyan (10:01)

You’re touching upon another important aspect. Many of colleagues and clinicians believe that if I go to the three months or the six months, I have to see the patient in three months, which is not true. Medication is given once every three months or six months.

We still need to see the patients in intervals that we feel is appropriate according to their treatment plan. The only issue is that we’re not going to spend a whole lot of time talking about medication and focus on other aspects. But part of that regular visit that maybe every two weeks, maybe every month to make sure they’re tolerating the medication, okay, there are no side effects.

And then what else are they doing? What else needs to happen in their treatment to move them forward? So you know, if you look at some of the, we do a PubMed search and looking at the efficacy of oral medications versus injectables, really establishes that patients on injectables tend to do better.

And it’s a simple reason, the medications in their system, it’s very simple. The medication that works for them is actually delivered to them. Rather than with pills, we prescribe, we hope they take it.

They sometimes take, sometimes don’t. How much they take, we don’t know. So.

Melissa Vitale (11:19)

We have to do a lot of digging. Yeah.

Optimizing LAI Formulations for Patient Needs

Roueen Rafeyan (11:22)

Again, further analysis and looking at efficacy of the long acting versus oral medications showing us that long actings actually tend to have better outcomes. This was an interesting study. It was patients stabilized on paliperidone, palmitate, then randomized to either continuing on paliperidone, palmitate monthly, or placebo.

The outcome was time to relapse. And also for our audience, it’s important to know relapse in these studies defined a little different. In our office, if a patient is agitated and psychotic and requires hospitalization, we consider that relapse.

Melissa Vitale (12:04)

Correct.

Roueen Rafeyan (12:05)

In these studies, for ethical reasons, any increase in PANS score is a relapse. If a patient comes in one day and they’re hearing more voices, that’s a relapse. If a patient comes in one day, they’re a little irritable, that’s relapse.

That’s for ethical reasons, because we don’t know who’s on the medication, who’s on placebo. For that reason, we have to yank them from the study and treat them conventionally. So with that low threshold of defining relapse, the patients who are on paliperidone, palmitate show significantly less relapse in the long timeline, which is almost 300 days.

Melissa Vitale (12:39)

Only 15 of 156 subjects on paliperidone palmitate once monthly had suffered a relapse, which is pretty incredible compared to the 141 of 156 remained relapse-free, and that’s amazing. So now here we’ll talk about some of the safety profiles of paliperidone palmitate. And these are things that we’re going to be monitoring our patients for once we do put them on the injection.

Some of the most common adverse events are injection site reactions, sedation, dizziness, akathisia. These are all things that even if we have patients on orals, except for injection site reactions, are things that we’re going to be monitoring for during our follow-up visits as well. Paliperidone also does have that prolactin elevating effect.

I don’t typically draw prolactin levels unless I see symptoms of prolactin elevation. What about you?

Roueen Rafeyan (13:31)

That is very common. Let’s keep in mind that prolactin has a diurnal secretion. So depending what time of day we draw the levels, it can be up and down.

And there are no standards as of when do we consider prolactin elevation. So most of us, our approach is clinical. If the patient is showing any symptoms that could potentially be due to increased prolactin, then we check and monitor.

For example, any changes in their menstrual cycle, any tenderness in their breasts, any galactorrhea. Those are the main symptoms that I clinically monitor. And if I see that, then definitely check the prolactin levels and then…

Melissa Vitale (14:15)

Go from there and make some changes if needed. We’re seeing José back in the clinic after he’s been on paliperidone palmitate once monthly for five months now. He has been keeping his appointments and he says he’s doing so much better.

He’s been consistent with his work and resumed his social activities. And we note improvement in his hygiene. He’s starting to look a lot better.

He does have an issue though. He says that he wants to go back home to see his grandma in Puerto Rico for her birthday. And he won’t be able to make it back in time for his next injection.

So this is where we had to sit down and discuss with him. He’s been stable on PPOM monthly for five months now.

Roueen Rafeyan (15:02)

So that is a good time actually to discuss the options. Because again, if initially had talked to him about that, if we are doing okay on the monthly, we have the option of going to either the three-month or the six-month version of the same medication. And now there’s a issue coming up that he’s going to be traveling, won’t be able to come back for his regular monthly follow-up injection.

It’s a great time to talk to him about, hey, the medication that you’re on is available in a three-month and a six-month.

Melissa Vitale (15:33)

The exact same formulation. And we can talk to him about how good he’s been doing. The risk of him not making it back in time for that next injection, that could be a risk to initiate a possible relapse as well.

So to maintain his stability, it would be a great idea to go to the once every three months or once every six months. And this is kind of like a reminder to him because we’ve also brought this up when he started the injections and it was something like a goal to look forward to in the future.

Roueen Rafeyan (16:03)

Now, here are some issues that we need to address. Sometimes patient caregivers will ask the question too, are you sure the medication was going to last three months? Are you sure the medication is going to last six months?

So a lot of education goes into that to ensure that it’s the same compound. The interval is different, but same medication. And just take precautions and educate them and reassure them that they will be okay.

Melissa Vitale (16:31)

Yeah, exactly.

Roueen Rafeyan (16:33)

So what you see here results from a one-year non-inferiority study comparing the six-month paliperidone palmitate to the three months. And as you see the studies, when you do almost head-to-head trials, you never see a superiority. Usually they’re designed based on non-inferiority, which means we take the three months.

We were familiar with it. It’s been around for a while. And then the six-month version is available.

Let’s look to see if it works as good. This is one year. And as you see, patients remain relapse-free at one year.

So 96.1% of the patients receiving the six-month version of the paliperidone palmitate remain relapse-free for two years.

Melissa Vitale (17:23)

Yeah, in the open label extension study. So that is pretty amazing. I mean, imagine 96.1% of your patients remaining relapse-free for two years.

Roueen Rafeyan (17:32)

And I always say, for those of us who treat schizophrenia, if I can keep 96% of my patients stable for two years, I have done good.

Melissa Vitale (17:42)

Yes, you have. Yes, you have.

Roueen Rafeyan (17:45)

So what are the side effects? What did we see? Because again, we want to know, patients want to know.

So what you see here are the side effects throughout the trials, various trials, with the three-month paliperidone palmitate, and also the six-month paliperidone palmitate. Good number of patients. As you see, the end numbers are a pretty good number of patients.

So we see about 12%, 13% upper respiratory tract infection, about 5%, 11% ejection site reaction, weight increases about 8% to 9%, headaches 5%, 7%, EPS 5% to 7%, akathisia 4%, and the numbers drop down.

Melissa Vitale (18:26)

I mean, what we see is really that no new safety signals emerged between the three-month and the six-month. So the side effects are very comparable to each other as well. And we want to make sure of that as well, because now we’re deciding to put our patient on every six-month injection.

Roueen Rafeyan (18:42)

Yeah, it is important to really know this data. Because again, once we give an injection, we can’t take it out. So let’s make sure that we know what to expect.

Melissa Vitale (18:51)

Exactly. So how is José doing now, right? After we have started him on, we ended up choosing to go with the once every six-month paliperidone palmitate, right?

Because he’s doing so well on his once monthly, we then decided to go with the six-month dose. He says that it was great to catch up with his family and old friends. He was super grateful to be able to attend his grandma’s birthday and not have to change his flights to come back home early for his injection.

His work is improving. And he’s been, at that point, consistently keeping his appointments. We ended up bringing him in at least quarterly.

That’s the max we’ll push out between injections, even though despite he’s on that once every six-month dosing.

Roueen Rafeyan (19:40)

I completely agree. I mean, it’s a good example of how having him on medication, stable medication, will keep him stable. And we can see him as frequently as we need to.

Case 2: Sarah

Melissa Vitale (19:51)

Exactly. Now we’re moving on to Sarah. She’s the next patient we’re going to be reviewing.

And Sarah is a 21-year-old college student who was recently diagnosed with schizophrenia six months ago after experiencing her second psychotic episode while she was home from school on summer break. She was started on oral risperidone after her diagnosis. And she did demonstrate clinical improvement and stability.

And she did tolerate the medication well for a while. What we see very often is she ended up going back to school and she stopped the medication due to the stigma that she felt after her roommate had found her medication and then Googled and found out what it was for. So she had a ton of self-stigma and she internalized those prejudices that others had about her externally.

She also had some issues with weight gain. She had gained four pounds. And Sarah is really big into exercise and diet.

And so this was really frustrating for her. So she decided just to dump her meds in the toilet. Of course, when our patients stop taking their oral medications, we often then will see relapse and symptoms of relapse.

And she ended up being re-hospitalized where she was restarted on her oral risperidone. And then, of course, counseled to maintain adherence with that. And we do see that a lot.

Our patients are hospitalized due to a relapse. And then a lot of times they’re actually restarted on that same oral medication that they were supposed to be on coming in. And the main thing I feel for that is because they weren’t taking it to begin with, right?

Roueen Rafeyan (21:41)

Yes, yes. So, you know, great case example of a new onset disease. As you all know, for the first six months, if someone is showing psychotic symptoms, it is still schizophrenia form disorder.

If it lasts past six months, then we get the diagnosis of schizophrenia. In my opinion, these are the crucial times to implement effective treatments. Because patients have a lot to lose again at this juncture.

And going back to our patient, Sarah, started college. My main treatment goal would be to keep her in college. If she keeps having relapses, that’s not going to happen.

So we have to keep her. Like any other college student, she’s going to be a female, college, going to be sensitive to weight gain. We have to be sensitive about that.

Stigma is another one that is going to take a lot of work with her, with her parents, regarding the diagnosis, acceptance of a diagnosis, to ensure effective treatment and treatment of life.

Melissa Vitale (22:52)

Medication, because a lot of patients will start feeling better and then they’ll stop their medication and not really believe that they have the diagnosis. So here, Sarah, we see her at our clinic, 12 days post-discharge of her second hospitalization.

Roueen Rafeyan (23:10)

Let me just talk a little bit about what I meant when I said there are consequences to relapse. And diagnostic. When a patient exhibits psychotic symptoms for the first time, we need routine labs.

Imaging is important. The main reason is we want to make sure there are no other lesions in the brain that could potentially cause psychotic symptoms. Could be a tumor.

It could be an arteriovenous malformation. Could be a cyst. It could be many other things.

So that’s why imaging is preferred. At least a CT scan, if you can get an MRI, shows you the brain better. By the way, when you do these imagings, many times it comes out okay.

There are no other lesions there. However, data shows us that patients with schizophrenia tend to have enlarged lateral ventricles.

Melissa Vitale (24:03)

Very interesting.

Addressing Side Effects and Stigma

Roueen Rafeyan (24:04)

So if I see that, along with the symptoms that have been there for more than six months, more likely for me to feel more comfortable going with the diagnosis of schizophrenia. What else do I need to rule out? Urine toxicology.

Has to be there. Usually when we order a urine toxicologist, the nine panel that shows us any of these compounds that you see here on this slide.

Melissa Vitale (24:31)

But now we have these designer drugs.

Roueen Rafeyan (24:34)

And designers, we have to actually be specific. For example, K2M spice, which are the synthetic cannabis, they are full agonist. As a result, the effect is more like a psychosis rather than the high that is achieved with regular cannabis.

So that requires a specification to get that. Kratom is another drug that is widely used everywhere. It can potentiate.

And many other drugs that are just being utilized these days. So some of that requires clinicians to stay on top of what is the newest fad of drug that is circulating in our community.

Melissa Vitale (25:19)

And really take a deep dive into our patients and ask them what they have been taking.

Roueen Rafeyan (25:25)

What else do we want to know? Regular routine labs, the CBC. We want to take a look at that to see if there’s anything abnormal there.

Followed by their lipid profile. And we need to just regularly call it the CMP to know how their liver is working, how their kidneys are functioning. Once again, it plays a role in what meds we were going to give them or if there are issues there anywhere.

And will also allow us to monitor them for any metabolic issues moving forward. And one of the best indicators of potential for metabolic issues are the triglycerides. So I really encourage all colleagues to pay attention to triglycerides.

So going back to our case, we do the clinical interview. We’ll go over the symptomatology, duration of the symptoms. Again, positive symptoms, negative symptoms.

We’re looking at all of these as of, as I say in PANS, general psychopathology symptoms. We want to know all about that. We want to know, establish her baseline functioning, what her interests are, and what are the concerns with the previous medication?

And why did she stop taking the risperidone as we discussed? And then in her case, again, young female, I would check her prolactin level, especially if she was showing some symptoms associated, increased prolactin.

Melissa Vitale (26:53)

She notes that she’s having some disruption in her menstrual cycle. She also notes galactorrhea, and she’s also still concerned about the weight gain and sedation. So we really now are thinking, okay, she has already stopped this medication once due to side effects.

Maybe this is not the medication for her, for this specific patient, right? She’s in college. We want to keep her sharp.

So we might want to think about a medication that might not have as much cognitive dysfunction or cause any hinder on that cognition and definitely avoid any medications are potent for histamine or histaminergic activity so that she’s able to stay alert and to complete her coursework. Because like Dr. Raphael said earlier, our goal is to really keep her in school.

Roueen Rafeyan (27:49)

Yeah, because we need to preserve functioning. And we know cognition is affected with this disease, even before the start of the disease. We don’t have any pro-cognitive medications to prescribe our patients.

So my approach is, let’s at least avoid worsening the cognitive problems. One way of avoiding that is not to use medications that are very histaminic. And histaminic properties have an impact on cognition.

Melissa Vitale (28:19)

Mm-hmm. So in the case of Sarah, we would likely draw a prolactin level just to see how high it is and make sure that she does have issues with high prolactin levels. And that’s what we would probably typically see.

And here we see that her prolactin level does come back at 146.4. So we’re going to think about then, what can we switch Sarah to considering her goals and her preferences on something that’s not going to interfere with her cognition, something that’s not going to significantly cause fatigue and something that is not going to be increasing her prolactin levels, right? So we’re going to explore here three options and kind of like our thought process of what meds are we going to consider for her? One of the three options would be xanomeline/trospium, which is one of our newer, it’s a novel combination medicine, M1, M4 agonist with peripheral muscarinic antagonist attached to it.

Another medication we’re going to think about that would fit what Sarah is desiring is cariprazine, which is a partial D2 and D3 receptor agonist. And also serotonin 5-HT1A. We have to remember that she has had issues with adherence to orals, right?

So the xanomeline/trospium, that does need to be taken twice a day. Cariprazine does need to be taken daily. These are both oral medications.

So we do have to think about a possible LAI option for Sarah to decrease or lengthen her time to relapse.

Selecting the Right Treatment Strategy

Roueen Rafeyan (30:15)

So we’re trying to choose from potential options, from all the options we have, what is she sensitive to? What are we trying to avoid? And what are we trying to achieve?

We don’t want her sedated. We want to preserve her cognition as much as possible. She’s complaining about weight.

So potentially choosing an option that is not going to cause weight gain.

Melissa Vitale (30:42)

Or a lower propensity to.

Roueen Rafeyan (30:44)

Lower, I like the way you put it. Exactly. So that narrows us down to a limited number of available options.

Another one that needs to be taken into consideration, she’s having symptoms due to increased prolactin. So we have to consider medication that actually doesn’t increase prolactin and hopefully potentially can help reduce this already elevated prolactin levels, which really limits it to the partial agonist. Among partial agonists, the only one that is available in the long acting is aripiprazole.

Melissa Vitale (31:18)

So these are the three medications, and we’ll go over our thought process of how we’re going to choose which medication that would be more most suitable for Sarah.

Roueen Rafeyan (31:28)

So one medication that is available is actually the newest one available to us with a novel mechanism of action is xanomeline/trospium. It’s a combo medication, which has been shown in short term and long term trials to have significant efficacy against positive symptoms, negative symptoms, and general psychopathology. So this becomes a good choice for a patient like Sarah, especially when we look at side effect profile.

Again, we don’t see the akathisia, we don’t see the EPS. A weight actually stays fairly neutral on this medication. However, it’s associated with some GI side effects.

It is a BID dosing against oral medication. So we’re talking about a college student that needs to remain adherent to a BID medication when she already was struggling with the first oral medication.

Melissa Vitale (32:24)

And also self stigma, right? So one of her main concerns would be to bring another medication in a bottle back into her dorm room.

Roueen Rafeyan (32:32)

Yeah, yeah. And having to explain that to friends and roommates as to why I am on this medication. Another medication that we may consider partial agonist should be considered here for her is cariprazine.

Again, looking at the data for cariprazine, three milligram, six milligram, we see this effective in reducing total PANS scores in their initial registry trials. It works, has the indication for schizophrenia. Actually here on this study, also see the 10 milligram aripiprazole.

Because we are thinking about, again, if we were thinking about long acting, aripiprazole another option as a long acting, so.

Melissa Vitale (33:15)

So these are pretty comparable in the decrease in PANS scores.

Roueen Rafeyan (33:20)

Side effects, what do we see with weight? Data from cariprazine studies, it seems like there is mean change of about two pounds, about 8% of the patients. EPS rates were about 15% versus 8% placebo.

Akathisia rates 9% at one and a half to three milligram. The second study, 19 to 13 milligram. As we go a little further up in different studies, numbers come up a little bit different.

So we see EPS, we see akathisia, there’s a little weight, but prolactin levels don’t go up on this compound and not a whole lot of impact on the metabolics.

Melissa Vitale (34:02)

Right, it’s pretty metabolically friendly. But we also have to remember, again, this is an oral medication.

Roueen Rafeyan (34:08)

Oral medication, yeah.

Melissa Vitale (34:09)

So now we move on to the aripiprazole once monthly.

Roueen Rafeyan (34:13)

So, you know, here now we’ve really narrowed down our choices to this patient will benefit from a long acting injectable. What do we know about aripiprazole? Again, we’ve had clinical experience with aripiprazole since 2002.

So number of years of experience with this compound. We know the efficacy of the oral medication, side effects of it. How about the once monthly injection?

Data shows us it’s actually effective against positive and negative symptoms. Generally, this total PANS scores in one of the early trials that shows significant 27 point reduction in PANS, which is quite impressive. CGI, which is clinician’s global impression, our eyes looking at the patient, not just the numbers and scales, one and a half point reduction in CGI, which actually quite significant.

So there is data. We have quite a bit of data about efficacy of this monthly injection. Side effects, again, familiar.

You see, actually look for the ones that are twice more than the placebo. Dry mouth at 4%. Diarrhea at 3% versus placebo 2%.

Average weight gain on 400 milligram was three and a half kilograms. Placebo was 0.8. Number of patients gaining weight more than 7% was about 21%. About 31 out of 144.

Mean change from baseline to week 12 with the prolactin was a minus number. The glucose levels really didn’t change that much. So as the clinicians, we have to weigh our options.

Evaluating Risk–Benefit Tradeoffs in Treatment Selection

Melissa Vitale (35:47)

I mean- The risk versus the benefit.

Roueen Rafeyan (35:50)

So what’s the benefit? We can have the effective medication in her system. Keep her symptoms stable.

Help her graduate college, which is the real goal. May come at the little cost of a little weight.

Melissa Vitale (36:07)

Decrease prolactin.

Roueen Rafeyan (36:08)

But prolactin will go down. And metabolically, we know we have a lot of experience with this compound. It doesn’t have a whole lot of impact on the metabolics.

Melissa Vitale (36:18)

So- And her metabolics, as we reviewed to start, are pretty good.

Roueen Rafeyan (36:23)

She was young. So, so far, so good.

Melissa Vitale (36:25)

And we can always monitor this. But this will hopefully keep her stable for longer. So we start, Sarah, on the once-monthly Aripiprazole.

And she’s open to doing that. And she comes back and sees us in the clinic for her next dose. She notes that her symptoms are well-controlled.

She’s no longer feeling fatigued and sedated during school. She’s able to complete a lot of her projects. Her prolactin levels have then- have now normalized.

So we do repeat those as time goes on, just to see- to make sure that they are going down with the Aripiprazole. And her galactorrhea has also resolved. We are, however, monitoring her weight because as we know, there is a chance that she can still gain weight with the LAI Aripiprazole.

So we are monitoring that. She hasn’t gained any additional weight from where she was prior to starting. So we’re now going to talk about possibly moving her to the every-two-month formulation of Aripiprazole in time.

We do want to let her know that that is an option for her as long as she maintains and does well with the once-monthly dosing.

Roueen Rafeyan (37:39)

So a very appropriate way of approaching this case. And our goal was to really go through a clinician’s eye based on the patient presentations, factors that influence our decision-making, and how do we end up choosing which medication for which patient. It was a very real-life patient that we wanted to discuss with our audience.

Hopefully this was beneficial for you.

Melissa Vitale (38:02)

Thank you so much.