Switching From Oral Therapy to Long-Acting Injectables
JUNE 19, 2020
Christoph Correll, MD: Long-acting injectable [LAI] medications, antipsychotics, have multiple advantages. Multiple studies and meta-analyses have shown that compared to oral medications, there is less chance of relapse with long-acting injectables, less risk of hospitalization. Patients have lower symptom levels. There is less exposure to medication because there's less peak-trough variation in terms of the exposure, which can also potentially reduce some [adverse] effects. Because there are fewer relapses, there is less secondary treatment resistance that can ensue. And mortality rates are lower. That's quite a package of advantages. If you told anybody, “Do you want treatment A or B, and B has all of these advantages,” everybody would say, “I want B.” But then the question is, “How is it given? Write the prescription for me.” “It’s not a prescription of an oral medication, it is an injectable.” “I don't want that.” “Well, let's discuss what the advantages are.”
When initiating a long-acting injectable, most of us want to know, at least for a period of time, that the oral formulation of that medication is both tolerated and efficacious. When we put together an expert panel, it was not clear among the experts and clinicians how long this initial period should last. Should it last just 1 or 2 weeks, when most of the initial adverse effects occur? Should it last 3 or 4 weeks, when you might be seeing more of a response? Or is the 2 week timeframe, when you see some response, sufficient?
Whatever the decision of the clinician is, knowing the patient, the acuity, or also the time that one has available to stabilize patients orally, it is important to move over from the oral formulation to an LAI. It’s easy when you come from the same drug that you’re testing out to the LAI, because there are dose levels that you can adjust. Some medications require booster injections. For example, paliperidone has a day 1, day 8, and then 1 month later the injection. Olanzapine pamoate has shorter injection intervals of 2 weekly or higher doses initially. Those do not require oral cotreatment.
Similarly, aripiprazole lauroxil has come out with a smaller dispersion formulation where you give 2 injections on day 1 and 1 oral dose of 30 mg, and thereby also obviating the need for oral cotreatment. Currently, risperdal consta, which is given every 2 weeks, requires for the first 3 weeks oral cotreatment with risperidone. And aripiprazole maintena requires 2 weeks of oral cotreatment. This could be a gap time where you're not sure whether the patient is taking it while the blood level is still rising. It’s important to make sure that family members can supervise the patient during that period, or that patients are in a setting where it's assured that they take the medication.
Some medications can also be switched from another oral medication directly to the LAI formulation. This is when you have knowledge that the medication was tolerated orally in the past and could have led to improvement. It’s important to know the differences of the pharmacology. If you come from a very tight D2-binding agent, be it haloperidol or fluphenazine, the first-generation LAIs or oral treatments, or you come from risperidone to a partial agonist, or you come from very sedating anticholinergic agents from olanzapine, clotiapine, or chloropromazine, then to an LAI, you would want to overlap in both these scenarios when the other drug is not so tight binding, or a partial agonist, when the new LAI is with a medication that is not as sedating or anticholinergic. You don’t want to abruptly stop the initial medication. That could lead to potential rebound phenomenon when you stop it too abruptly. An overlap and a slow taper of the initial medication can be helpful.
Transcript Edited for Clarity