Dosing LAI Antipsychotics for Schizophrenia

Transcript: John M. Kane, MD: Sanjai, please share with us how you switch a patient from an oral to a long-acting injectable antipsychotic.

Sanjai Rao, MD: I start the long-acting injection [LAI] as early as possible in their treatment course. I prefer they are on an oral [therapy] for a brief period of time. The label for most drugs says the main concern is to establish that there is a lack of hypersensitivity. This involves giving people 2 oral doses on the low end of the FDA range. This ensures there won’t be an allergic reaction to the drug. Clinically it’s nice to go a bit beyond that label before starting a long-acting injectable. Optimally you’d want to establish that there’s minimal efficacy. Even a small symptomatic improvement in the first 1 to 2 weeks would be ideal. A 20% improvement in 1 to 2 weeks would suggest a continued improvement later in treatment. That’s the goal in an acute hospitalization. We’re looking for an indication that the molecule and the pharmacodynamics of that molecule are going to be good for this patient. Once we establish that we are comfortable initiating a long-acting injection.

If you have the luxury of a longer hospitalization and it’s established that the molecule is working, you can determine what dose of the molecule works. Once it’s established the drug is working for this patient, you want to transition them to an LAI. It’s important to note that most every long-acting injectable has a loading regimen. The loading regimen typically involves multiple injections and possibly an overlap or sometimes both. The goal is to quickly get their plasma levels up nearly equivalent to the levels they were getting when they were on orals. Some long-actings require a couple of injections in a single day. Other injections could be dosed a couple of weeks apart.

And some of them have longer durations than that. If you’re coming from a high dose of oral medication, you might want to have an oral overlap in between the loading regimen, to make sure that their levels don’t drop off too much. If they’re used to a high dose of medication, then you give them their injection of long-acting. If you don’t give them any oral initially, their plasma levels could drop and you might see a momentary worsening of symptoms.

Once you’ve loaded them up, you have to pick a maintenance dose. This is where having data from an oral trial will help you. If you’ve established that this medication is going to work and decided on a long-acting, you’re going to have to guess at the maintenance dose, depending on how well they did on the oral drug, the dose you were using, and if they were improving. This helps determine the correspondence between an oral dose and a long-acting dose.

For a given dose of a particular medication, we have a reasonable idea of what kind of long-acting dosing it’s going need to maintain that level. If you’ve done a small trial, you can make your best guess as to what dose is going to approximate their final dose.

If you had the opportunity to do a longer trial, they were on an oral medication for 2 or 3 weeks before you put them on an LAI. And if you monitored them, you have a good idea of what oral dose is going to work for them, and you can directly convert that to a long-acting level.

Finally, if you’re using higher doses of long-acting, you may want to consider getting plasma levels along the way. Essentially this is predictable when using population pharmacokinetics. Many companies that make long-actings have done that work for us and given us the correspondence between oral and long-acting doses. But there is always some variability in excretion and metabolism. There may be an individual variability in how they process a particular drug. If you’re giving the dose that you think should be working and it’s not, then 1 possibility is that they’re just not seeing the drug levels they should. Using their plasma levels can determine this. It’s particularly useful with some of the older medications, but it can also be not useful with the newer ones.

John M. Kane, MD: It’s important to note that I don’t want people to get the sense that this is complicated. I’ve heard some clinicians say, “I’m afraid,” and hesitant to switch from oral to long-acting because I don’t know what the dose is, it seems like a complicated challenge. I would say it’s not that complicated. We know a lot about the doses of these medicines. In fact, we’re in a better position to control the dose when we’re giving it via a long-acting formulation. When we assume that many of our patients are not taking oral medicine consistently or in the dose prescribed, we don’t know what’s going on. I would argue this should not be viewed as an obstacle.

Sanjai Rao, MD: Agreed. I didn’t mean to make it sound complicated. Most of the oral medications that have long-acting correspondents have really clear instructions for loading and maintenance dose. If you have a patient on a particular dose of an oral medication, it’s 1 web search away, even if you know nothing about it. Figuring out what’s the loading dose of the corresponding long-acting and how do you choose the maintenance dose based on the oral dose they were already on.

John M. Kane, MD: Long-actings, in my opinion, are safe drugs, as we know what the adverse effects are. We know what to expect over time. We will probably want to titrate the dose if necessary. We have a lot of experience with these medicines, and we can manage them.

Transcript Edited for Clarity