Savvy Psychopharmacology

Discontinuing a long-acting injectable antipsychotic: What to consider

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Practice Points

Mr. R, age 29, was diagnosed with schizophrenia 6 years ago. To manage his disorder, he has been receiving paliperidone palmitate long-acting injectable (LAI) 156 mg once a month for 2 years. Prior to maintenance with paliperidone palmitate, Mr. R was stabilized on oral paliperidone 9 mg/d. Though he was originally initiated on paliperidone palmitate due to nonadherence concerns, Mr. R has been adherent with each injection for 1 year.

At a recent visit, Mr. R says he wants to discontinue the injection because he is not interested in receiving an ongoing injectable medication and is not able to continue monthly clinic visits. He wants to take a daily oral antipsychotic again, despite the availability of longer-acting products.

A paucity of evidence exists regarding the discontinuation of LAI antipsychotics and the next steps that follow in treatment. There is neither a consensus nor recognized guidelines advising how and when to discontinue an LAI and restart an oral antipsychotic. A recent systematic review and meta-analysis evaluated different maintenance treatment strategies; however, switching from an LAI antipsychotic to an oral medication was not a focus.1 In this article, we outline a possible approach to discontinuing an LAI antipsychotic and restarting an oral formulation. Before discontinuing an LAI antipsychotic, clinicians should review with the patient the risks and benefits of switching medications, including the risk of decompensation and potential adverse effects.

Switching to an oral antipsychotic

The first step in the discontinuation process is to determine whether the patient will continue the same oral medication as the LAI antipsychotic or if a different oral antipsychotic will be initiated. Next, determining when to initiate the oral medication requires several pieces of information, including the oral dose equivalent of the patient’s current LAI, the half-life of the LAI, and the release mechanism of the LAI (Table 1).2-5 To determine the appropriate time frame for restarting oral treatment, it is also vital to know the date of the last injection.

Long-acting injectable antipsychotic medication pharmacokinetics

Based on the date of the next injection, the clinician will utilize the LAI’s half-life and its release mechanism to determine the appropriate time to start a new oral antipsychotic. Research demonstrates that in patients who have achieved steady state with a first-generation antipsychotic, plasma concentrations stay relatively consistent for 6 to 7 weeks after the last injection, which suggests oral medications may not need to be initiated until that time.6-9

For many second-generation LAI antipsychotics, oral medications may be initiated at the date of the next injection. Initiation of an oral antipsychotic may require more time between the last injection dose and the date of administration for oral medication due to the pharmacokinetic profile of risperidone microspheres. Once a patient is at steady state with risperidone microspheres, trough levels are not observed until 3 to 4 weeks after discontinuation.10

Previous pharmacokinetic model–based stimulations of active moiety plasma concentrations of risperidone microspheres demonstrate that 2 weeks after an injection of risperidone microspheres, the concentration of active moiety continued to approximate the steady-state concentration for 3 to 5 weeks.11 This is likely due to the product’s delay in release being 3 weeks from the time of injection to the last release phase. Of note, there was a rapid decline in the active moiety concentration; it reached nearly 0 by Week 5.11 The same pharmacokinetic model–based stimulation demonstrated a steady and slow decline of the concentration of active moiety of paliperidone palmitate after discontinuation of the LAI.11

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