Optimizing Schizophrenia Treatment Through LAIs

In this podcast taken at a recent live Q&A session during the virtual Psych Congress Regionals, Psych Congress Network's Schizophrenia Section Editor, Leslie Citrome, MD, MPH, answers questions about the utility of long-acting injectables (LAIs) in treating schizophrenia. Dr Citrome explains why LAIs are never a last resort, how to choose the specific formulation to use, overcoming a patient's aversion to needles, and offers options as to where clinicians can learn how to incorporate LAIs into their practice.

Saundra Jain, MA, PsyD, LPC, adjunct clinical affiliate, University of Texas at Austin School of Nursing, moderates the discussion.

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Read the Transcript:

Saundra Jain, MA, PsyD, LPC: Hey, Les. Great to see you this evening.

Leslie Citrome, MD, MPH: Great to see you, too.

Dr Jain: Well, we have a lot of questions from our attendees, so I suggest we just jump right in and get started.

Dr Citrome: You bet.

Dr Jain: This is the most popular question. Here we go. Are LAIs a last resort?

Dr Citrome: No, absolutely not. In fact, they should be considered much earlier in the course of someone's treatment journey. So let's say someone is diagnosed with their first episode. They need to be told that there are ways of getting medicine that are  much more convenient, consisting of something taken once a month, once every two months, once every three months, or once every six months are all possibilities today. So they're not stuck with taking something by mouth every day. Wouldn't that be interesting? Would they like to hear more about it? And we would encourage people in their first episode to be transitioned over to a long-acting injectable. That will ensure the best possible way of getting treated. They'll have the medicine onboard that will keep them well as best as possible.

First episode is really tough. You feel better and you feel you might not need your medicine. You may skip a day or two, and then that's the end of that. With a long-acting injectable, you have more leeway here. If someone wants to stop the injection, you can have a more leisurely conversation about it, and it's not a fait accompli.

Dr Jain: I love this question because, Les, you know, I'm a type-1 diabetic. And even as recently as five years ago, I had a clinician once say to me, "Oh, so you use a pump. You must be really sick." And I said, "No, no, no. I use a pump, and that's why I'm very well. But thank you for asking." It sounds like this is the same thing, that we wouldn't want to see LAIs as last ditch effort. This should be on the front end of our decision making.

Dr Citrome: So I like to say if you prevent the relapse today, that could make a difference for a lifetime.

Dr Jain: Beautifully stated. So here's a really interesting question. How accessible are LAIs in certain settings? They offer an example, like in prison.

Dr Citrome: Yeah, it's a good question. It differs from place to place, and it differs also in terms of what kind of difficulties is that place having with the administration of medicines. In many settings like that, there is quite a bit diversion going on with the medicines that are given orally. And it's tough to actually witness the oral administration of medicine for an incarcerated individual. It's very time-consuming, and yet it's also risky to just give the medicines out, because they could be cheeked and then secreted away for some other purpose. This is a real issue.

Long-acting injectables avoid that, and it can be quite simple to administer. It actually makes everyone's life easier. There are injectables that can be given less frequently than once a month, as I mentioned just a few seconds ago. Every two months, every three months, every six months are all possibilities today. And that can make the running of the institution much more smooth and helps the incarcerated individual out, in terms of keeping them well.

Dr Jain: Yeah.

Dr Citrome: Now in terms of funding, it's interesting. From time to time I visit places, mostly local county facilities, and they tell me that they offer branded products, expensive products. And I say, "How do you do that? How do you afford it?" They say, "Well, we just bill the other county that's sending us the individual so it gets done." I never thought that would be a way to provide medicine, but it is. And in some states, where not in large states, not all counties provide all the services, it actually opens up opportunities to provide what patients need.

Dr Jain: Yeah, those are such important points. I'm going to turn our attention to a really important medication question, and this clinician wants to know: "How do I choose between risperidone and aripiprazole?"

Dr Citrome: Well, when someone is on a medicine orally and it comes in a long-acting injectable, that's the one I usually gravitate towards, provided that they are doing reasonably well on that oral medicine and it's tolerated reasonably well. So if they're on risperidone or aripiprazole oral, well that's a no-brainer. That's what they're going to get. And we use a lot of aripiprazole, a lot of risperidone, so it's not an uncommon scenario to encounter patients taking pills, either of those two.

Now, what if they're not tolerating the medicine that they're taking, or they're not doing well enough? Then I think of something kind of different than what they're receiving. Well luckily for us, risperidone and aripiprazole are very different, and if one doesn't tolerate or respond to one, well that's a logical choice to try for the next one. And they both come in LAIs.

Now risperidone, you should know, and I think most people do, that paliperidone is the active metabolite of risperidone. It's 9-hydroxy risperidone, so when you give risperidone, you're essentially also giving paliperidone. And we have a whole array of drug choices in the risperidone-paliperidone family, so to speak. We have the very old-school risperidone microspheres. I don't generally suggest giving that anymore, because it needs to be administered every two weeks, and you need a three-week oral supplementation period when you start it and when you change the dose. So it's not very convenient. Plus, you have to keep it in a fridge, and it needs to be reconstituted. It's not all that easy.

But paliperidone palmitate? Well, prefilled syringes, no need for refrigeration, small needle boars, and comes in an array of doses and options to administer every three months or six months once they're stabilized on the once monthly. And we have a subcutaneous formulation of risperidone available, as well. So that's new. That's different. And we'll have more formulations in the risperidone-paliperidone family in the not-too-distant future.

With aripiprazole, we have a couple of choices, too, to consider. Based on the amenities of care, as I like to say, these formulations (aripiprazole monohydrate and aripiprazole lauroxil), differ in terms of the dosing available, where you inject it, and the injection interval. One of them can be given every two months, for example.

Now beyond that, we are kind of limited. Olanzapine pamoate is available if you are willing to have the observation period. It requires a three-hour observation period after an injection because of the risk of post-injection delirium sedation syndrome. Now, it's uncommon. It's 0.07% of all injections. But it's a requirement. It's part of the REMS. So there's some places that offer it, but most places do not.

And then if you really are limited, well we still have the first-generation long-acting injectables. But be mindful. They're not optimal. Patients will often need some treatment for drug-induced parkinsonism, and there are sometimes shortages of these first-generation LAIs, and we have to switch to something else when that happens.

Dr Jain: Well, I'm so glad that you spoke a bit less about olanzapine pamoate formulation, because that was the very next question. Very nice segue into answering that question for our clinician. This is a popular question, but I find it also very interesting. They're asking, "Are there training courses that teach clinicians how to actually inject LAIs?"

Dr Citrome: Well, I'm glad that that question was asked, because at the next US Psych Congress in New Orleans, coming up very shortly in September, there will be such a training session. So if you are really interested in this, I urge you to attend the conference, find out when that training session is, and attend.

Now that aside, if you work in an institution, you can learn how to inject from someone who does the injections. I don't think they'll be shy at showing you the nuts and bolts of it. And the different manufacturers of branded LAIs will make nurse educators available to teach you how to inject. Now, keep in mind each product has a different protocol for injection. Some products are injected quickly. Some need to be injected more slowly. Some are injected in the muscle, and one is injected subcutaneously, actually, in the abdomen. So it's different from drug to drug. And part of, also, the differences are the reconstitution requirements. Some are more complicated than others.

Dr Jain: All right. Yeah, so glad you pointed out that we're going to have a session at Psych Congress at our national meeting. I hope lots of people come to that, and we can all learn together. All right, I know this is such a big issue around non-compliance and LAIs. I know a lot of times my patients, even in my psychotherapy practice, talk about issues around the shots, fears about pain, all of that. This clinician is saying, "I have many clients who are non-compliant with their LAI. Can you specify some of the side effects with non-compliance when taking LAIs? And is it safe to just start back up when there's been a period or a lapse in the shots?"

Dr Citrome: So, interesting observation. People non-compliant with LAIs means they're late for their injection, but that may not be unusual for that person who has difficulty with other commitments, as well. And it may not necessarily be related to the injection itself. May be related to other things going on in their life and some practical obstacles of getting to the clinic and keeping that appointment. That's certainly possible. I would urge you to follow up with the injection as quickly as possible. Some products actually have a pretty generous forgiveness period where someone missed their injection by a month. The solution is, well, you just give the injection. You don't really worry about this too much. You don't adjust the dose or anything. There's no oral supplementation. You just give that injection.

Whereas other products, the leeway is briefer, like a week or so. In which case, you don't have that much time before you have to restart any initiation process that ordinarily is associated with that product. So that could mean oral supplementation. It could mean an additional injection. It really does depend on the individual medicine that is prescribed for that person. But I would explore reasons as to why it is difficult to get to where you need to go for that follow-up visit and for that injection.

I serve as a consultant to our county's Assertive Community Treatment Team (ACT Team). And there we have the benefit of many different providers and people who can go out and locate that person and give that injection, will go to that person's home, will meet them somewhere else. They'll get their injection. But if you don't receive that degree of ACT services, then it's more difficult. There is levels of care that are below ACT, such as intensive case management, and that simple case management that can help an individual if they're hooked up with a healthcare system.

Dr Jain: Yeah. Les, I'm thinking about, again, just patients in practice who typically are just frightened of needles and pain and just have this immediate reaction, "No, it's not an option." How would you advise us, guide us, in talking to those particular patients who are just really frightened about needles?

Dr Citrome: Yeah, so what I do is I demystify the process. I show them the syringe and the needle that's attached to it. And if they have tattoos, talk about those, because they hurt a lot more. And if they have a history of IV drug abuse, well, IV injections of substances of abuse, that's technically very difficult. And what we're proposing is something actually pretty simple. And I talk about the flu shot that they may have received. It's sort of like that. And I talk about some of the research that's been done, looking at different antipsychotics that are injected and asking patients to rate the pain from zero to 100 and telling the patient, "Do you know what? You know what they rated that pain on their first injection was? Seven out of 100. And what about the injections that happened after that? About five out of 100. With zero being no pain and 100 being excruciating pain, five and seven are pretty low numbers there. So maybe it's something worth considering and not be frightened about the needle. But again, I'm not going to force you to take it. It's going to be up to you. It's your decision, but I think you need to know all of the facts."

Dr Jain: Beautiful. I like all those suggestions. We have about a minute left, Les. I want to offer this last question. This clinician wants to know, "How do you switch from one LAI to another?" How do you do that?

Dr Citrome: Well, you need to take into account what is recommended within the new LAI, in terms of an initiation process. And you just need to be mindful about what they're coming off and what they're coming onto. You want to make sure that they have sufficient antipsychotic on board. Now, that's particularly important when you're switching because of a tolerability issue, but you have reasonable efficacy. You don't want to lose efficacy by having too low a plasma level of an antipsychotic.

nIf you're switching because of poor efficacy, well then, it's a moot point, isn't it? Because whatever they're receiving is simply not working, and then you just go ahead and do what you need to do with the new medicine, with all the attendant initiation processes ongoing. So it's basically taking into account what they were on, what you want to put them on, what's generally recommended when you start the new product, and just making sure that you time it so that any blood levels of their antipsychotic won't be too low.

Dr Jain: Great. Great advice, Les. I want to thank you for joining us this afternoon, and I have very good news for everyone. We are in the home stretch now. So I'd like to invite everyone to join us for the last session of the day on rapid-acting antidepressants, and that session's going to be starting in just about 15 minutes. We'll see you very soon.

Leslie Citrome, MD, MPH, is clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla, New York, and adjunct clinical professor of psychiatry, Icahn School of Medicine at Mount Sinai in New York City, New York. In addition to his academic positions, he has a private practice in psychiatry in Pomona, New York, and is a volunteer consultant to the Assertive Community Treatment team/Mental Health Association of Rockland County. He is a Distinguished Life Fellow of the American Psychiatric Association and a Fellow of the American Society of Clinical Psychopharmacology where he currently serves as President. Dr Citrome is editor emeritus, International Journal of Clinical Practice, where he was editor-in-chief 2013-2019; psychiatry topic editor for Clinical Therapeutics; editor for the American Society of Clinical Psychopharmacology Corner in the Journal of Clinical Psychiatry; section editor for psychopharmacology for Current Psychiatry; and also serves as an editorial board member for several other medical journals.