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Elevating the Treatment of Bipolar Disorder and Schizophrenia: Examining the Role of LAIs

January 21, 2021

In this video, Leslie Citrome, MD, MPH, discusses the use of long-acting injectable antipsychotics in the treatment of schizophrenia and bipolar disorder. Dr. Citrome is Clinical Professor of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla.


Read the transcript:

Hello, I'm Dr. Leslie Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College. I'd like to talk with you a bit about antipsychotics and specifically long‑acting injectables. Antipsychotics are the foundational treatment for schizophrenia. We also use them in people with bipolar disorder and schizoaffective disorder.

However, it's not always so easy to figure out which one to select. And sometimes, it's even difficult to bring up the topic of long‑acting injectable formulations. In essence, they're very helpful. They can assist with adherence, leading to better outcomes. And in the end, many patients actually prefer long‑acting injectable formulations, especially after gaining some experience with them.

Now, nonadherence and partial adherence are common. And, we expect to encounter it in about half of our patients with schizophrenia. Adherence can fluctuate over time and is often considered part of the illness.

There are many patient‑related risk factors for nonadherence that we pay attention to, including poor insight, a history of prior nonadherence, and negative views of medication treatments.

We'll also be on the lookout for substance use issues and cognitive impairment. We also need to be mindful about our treatment‑related risk factors for nonadherence. And these include the adverse effects of the medicines that we prescribe, or perhaps inadequate reduction of symptoms.

There are also some environmental, social, relationship, and pragmatic factors for non‑adherence. These include the absence, perhaps, of a supportive family environment, and/or a community that stigmatizes psychiatric disorders and/or treatments.

There may be a lack of transportation to get to the pharmacy. There may be a lack of a place to safely store one's medications. And there may be delays in filling prescriptions.

Unfortunately, nonadherence does increase the risk for relapse and rehospitalization. It also leads to inadequate treatment response and perhaps, in some patients, aggressive behavior, suicide, and substance use.

Long‑acting injectables eliminates the uncertainty we have about adherence to oral medications. Long‑acting injectables can be administered every two weeks or every month or even longer, depending on which one we're thinking about prescribing.

Although not every oral antipsychotic is available as a long‑acting injectable, we now have many more options than we used to 20 years ago.

We do have some first generation antipsychotic long‑acting injectables, for example haloperidol decanoate. However, that drug can be problematic, particularly if someone needs ongoing treatment with, let's say, an anticholinergic medicine like benztropine. Benztropine is bad news for people who need to take it on a regular basis because it can impair their cognition. It also can make [tardive dyskinesia] worse if they have TD.

I like to avoid first-generation long‑acting injectables as often as I can. I'll think about using the second-generation long‑acting injectables.

Depending on where you practice, you'll have a variety to choose from. I say this because one of the choices is actually olanzapine, olanzapine pamoate. We often forget about that one, but it does require a three‑hour observation period after each injection because of the issue of post‑injection delirium sedation syndrome, so it's not available everywhere.

Far more easy to prescribe and actually implement in one's practice is the assortment of risperidone or paliperidone long‑acting injectable formulations, as well as the two aripiprazole long‑acting injectable formulations.

As far as risperidone goes, we know that it's metabolized to paliperidone. So I, in my mind, have an equivalence between risperidone and paliperidone. I look towards whatever long‑acting formulation makes sense for that individual. And I do know that there is a formulation of paliperidone palmitate that eventually I could use every 3 months for some of my patients. That can be quite convenient.

We have two competing formulations of aripiprazole, aripiprazole monohydrate and aripiprazole lauroxil. They do differ in terms of how often they need to be injected, the requirements for oral supplementation, and what happens if they're late for their injection.

Now, what's common to all the second-generation long‑acting injectable formulations is that they're based in water as opposed to the first-generation LAIs based in sesame seed oil.

Now, there's one kind of exception that's different from the others, and that's risperidone subcutaneous injection. Of course, that's not based in water. It's based on a, a polymer of sorts where you inject the medicine, in under the skin and then risperidone is released over a period of a month in 2 phases, immediately and then more prolonged. So that's a little different technology‑wise.

Now, as with all second-generation antipsychotics, drug-induced Parkinsonism and dystonia can be largely avoided. And this a big advantage over the older, first generation, LAIs. And you don't generally need an anticholinergic medicine to be coprescribed.

If you do, I would think about using something else, or perhaps lowering the dose. Remember, you want to avoid having to use an anticholinergic on a daily basis.

Now, choosing amongst the different LAI antipsychotics is also based on pragmatic concerns. For example, you want to continue giving what they've been receiving orally, but sometimes you'll switch to another member of that family.

For example, if they're taking oral risperidone, you do have some choices about going with risperidone microspheres, risperidone subcutaneous, or paliperidone palmitate.

But there's other considerations, as well, besides what molecule they were receiving before. That is the, what I call, the amenities of care. Now, what do I mean by that?

Well, there are 10 questions I ask myself when thinking about long‑acting injectable formulations. These questions include, how often are the injections administered? Probably the least often is desirable. What is the needle gauge? Usually the smaller the needle, the better. What is the injection volume? Usually, the smaller the volume the better.

Is there a choice of injection site? I like to have choices. Does this product require reconstitution? If I have to reconstitute this and if it takes a long time, well, I may really not be so enthusiastic.

Is oral supplementation required? Well, that could be a concern in someone who is kind of unreliable in adhering to instructions about taking oral supplementation for the 2 weeks or 3 weeks that is necessary.

Does this product need refrigeration? Now, this is an important question if your office doesn't have a place to store it. Are there any special requirements for observation? Well, right now, there's only one long‑acting injectable that does require observation, and that's olanzapine pamoate.

And then, lastly, are there any important drug/drug interactions and can they be easily resolved, perhaps by adjusting the dose?

Now, there are some other concerns about adherence with long‑acting injectables. If they don't come to the clinic or your office for their injection, that's a problem. And you need to find them and get them back on track.

The nice thing about long‑acting injectables is you have some time to do this. It's not like with an oral medicine where the plasma levels drop rather quickly. You do have some time.

Each of the different choices have different suggestions on how long you have, though. And, some drugs have a longer grace period, so to speak, after being late for your injection. I like to look at that aspect of the formulation, as well.

In the end, we are concerned about the well‑being of our patients and keeping them as symptom‑free as possible. Now, usually, that means the foundational antipsychotic needs to be on board, particularly for our patients with schizophrenia, where we don't have any other options today. And I'm going to look towards long‑acting injectables as a way of providing that for them.

Receiving a long‑acting injectable has many benefits. For us, it eliminates the worry that we have about adherence and for the patient, it could be really convenient.

Now, let's take a step aside for a moment and think about what it's like to be someone taking a medicine every day for something that you don't always acknowledge as a problem and being nagged by a loved one. "Did you take your medicine? Did you take your medicine? Did you take your medicine?"

That's stressful. If we can eliminate that stress and give everyone peace of mind with a long‑acting injectable formulation, then I think we'll advance the care of our patients. So, eliminating this guesswork about adherence is a big plus. And in the end, as I mentioned earlier, patients often prefer them, provided that they are offered this as a choice.

Well, I hope my commentary has been useful for you and I appreciate your time listening to me. Thank you so much.

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