Schizophrenia: Nuance in Switching to Long-Acting Injectables

Peter L. Salgo, MD: Let’s say, based on what you’ve said, somebody watching this broadcast says, “Well, these long-acting injectables sound interesting. I have a patient on oral medication that maybe already relapsed once because of failure to take the pills.” How do you go about changing, switching, just mechanically from an oral dose to an injectable?

John M. Kane, MD: It’s really not difficult. The first thing you want to do is decide which medication you’re going to use because we have a choice of different medicines. Again, what’s the injection interval? Then you’re going to think about the dosage of medications the patient has been on. You’ll make a decision about what’s a reasonable starting dosage, and depending upon which medication you choose, there are different strategies for switching. In some cases, you need oral supplementation for a period of time. In other cases, you don’t. You’re going to want to read the package insert. You’re going to want to understand the characteristics and the pharmacokinetics of that particular drug and then make a decision about dosage and injection interval.

Peter L. Salgo, MD: How do you monitor this? I mean, you’re talking very smoothly about how you’re going to measure these things. In the clinical setting, how do you go about monitoring and titrating these things?

John M. Kane, MD: You’re always going to be titrating against clinical response. You want to get someone up to a therapeutic blood level, so you’re going to follow the package insert in terms of dosage recommendations. You’re also going to be monitoring the patient for adverse effects and for clinical response. In many cases, these drugs require some time to get to a steady state. So you’re going to be aware of that. You’re going to continue monitoring the patient as you would on oral medicine, except the difference is you now know that the patient is definitely getting the medicine. One of the challenges we have when someone is on an oral medicine is if they’re not responding well—they’re having symptoms that are not under control—we’re asking ourselves, “Well, did that medicine not work, or were they not actually taking it?” That can be a difficult thing to figure out.

Peter L. Salgo, MD: I’m going to ask you a personal question as a practitioner. There are a lot of formulations out there. Let’s talk about the injectables, specifically long-acting injectables. What do you as a clinician do? How do you make the decision as to which of those drugs to use?

John M. Kane, MD: It’s not that dissimilar from the decision about oral medications. Now, we have slightly fewer long-acting formulations than we do oral medicines, but we’re going to talk to the patient about their past experience with different medications. We’re going to understand what adverse effects they’re either particularly sensitive to or concerned about. We’re going to make a judgment about the characteristics of a particular drug. We’re also going to look at the injection interval. We’re going to try to decide what makes most sense for that patient. Then we’re going to institute a trial of the drug that we think makes the most sense.

Peter L. Salgo, MD: Not treating this disease specifically, you’re the perfect person to tell me if I’m crazy if I were to decide to pick the 1 with the longest half-life. I don’t want them coming back every week, every month, and I’d like this to be relatively smooth.

John M. Kane, MD: Well, you’re not going to start out with the longest half-life because first, you really can’t. The 1 that has a 3-month interval, you really need to treat the patient for 4 months with the once-monthly dosage.

Peter L. Salgo, MD: Is that because you need to build up drug level?

John M. Kane, MD: You also want to make sure they tolerate the medicine.

Peter L. Salgo, MD: I get it.

John M. Kane, MD: But eventually you can get there. I think that may be your plan. My point is just you may not go there immediately. That may be the long-range plan. It’s like any decision about choosing a medicine. You’re going to base it on prior experience with that drug or perhaps a relative had a similar drug or whatever. Unfortunately, there is an element of trial and error in the use of antipsychotic drugs when we’re starting with a new patient who has never had antipsychotic medication. We don’t necessarily know what they’re going to respond best to. Sometimes we have to try 1 or 2 drugs. People are moving now more toward the notion that if somebody fails on a couple of different drugs, we really should consider a trial of a long-acting formulation instead of just waiting until people have relapsed multiple times because of nonadherence.

Peter L. Salgo, MD: Yeah, you pointed out that the assumption of the perfect doctor is he or she has the perfect plan with the perfect drug. Therefore, the drug is the drug failure and not the patient’s failure.

John M. Kane, MD: Right.

Peter L. Salgo, MD: But in reality, if I hear you correctly, a lot of the time the failure—is it pejorative to say a patient failure? Let’s say a patient’s failure to comply precisely; we’ll blame the ether for this. If you can give something that makes it easier for the patient to comply, it’s better in the long run. Is that fair?

John M. Kane, MD: Yes, absolutely. Yeah, I think that’s very fair.

Transcript edited for clarity.