Converting oral to long-acting injectable antipsychotics: a guide for the perplexed

Abstract

There has been increasing recognition that antipsychotic nonadherence is common across all stages of schizophrenia, starting from the first episode. Moreover, numerous meta-analyses of the existing literature indicate superiority of long-acting injectable (LAI) over oral antipsychotics when one adjusts for the greater illness severity and duration among patients in LAI antipsychotic trials. The increasing availability of LAI antipsychotic options has raised interest in converting patients from oral medication; however, the successful transition from oral to the comparable LAI antipsychotic requires an understanding of the current extent of antipsychotic exposure, the kinetics of the LAI preparation, and the expected plasma levels achieved by the LAI formulation. The purpose of this article is to provide, in a concise format, the essential information for converting patients to the LAI forms of haloperidol, fluphenazine, risperidone, paliperidone, olanzapine, and aripiprazole from the comparable oral medication, and how the use of plasma antipsychotic levels can be invaluable for this process.

Monitoring and improving antipsychotic adherence in outpatient forensic diversion programs

“…15 For patients who respond to an antipsychotic that is available as an LAI, conversion to the depot formulation is appropriate and can be guided by manufacturer recommendations, and a recent review paper is dedicated to this topic. 16 Unfortunately, most antipsychotics and the commonly used first-line mood stabilizers lithium and divalproex are available only in oral forms. The use of pill counts can rapidly identify poor oral medication adherence and permit interventions to avert the psychiatric and forensic consequences.…”

“…Detailed information on the use of these LAI antipsychotics and unique safety issues with olanzapine pamoate (Relprevv ® ) can be found in recent reviews. 16,27 While some patients will refuse an LAI, and others might not respond to or tolerate the available LAI options, successful conversion to an LAI vastly simplifies concerns about antipsychotic nonadherence. The failure of a patient to be seen at the prearranged time for the injection immediately alerts clinical staff that something is amiss.…”

“…Even when adherence is assured on the basis of regular pill counts or use of an LAI formulation, there is extensive interindividual variation in antipsychotic metabolism, and a wide range of antipsychotic levels at which patients respond. 16 When adherence is removed from the equation, inadequate response can only be due to one of two issues: subtherapeutic plasma antipsychotic levels (due to underdosing or kinetic interactions) or treatment resistance. 30 Before deciding that an adherent patient who failed two or more antipsychotics is treatment resistant, subtherapeutic antipsychotic levels must be ruled out.…”

Practical considerations for managing breakthrough psychosis and symptomatic worsening in patients with schizophrenia on long-acting injectable antipsychotics

“…A more detailed description of the PK/PD properties and interactions of LAIs is reviewed elsewhere. 14,[27][28][29]…”

Size matters: the importance of particle size in a newly developed injectable formulation for the treatment of schizophrenia

“…A loading dose approach has been used for other LAI antipsychotic formulations (e.g., haloperidol decanoate, fluphenazine decanoate, and paliperidone palmitate); however, this approach would not work for AL because this lag time is independent of initial dosing strength and, therefore, would not appreciably change the time delay that occurs before the achievement of relevant aripiprazole levels. 10 Instead, a second option is used to address the lag time between the first AL injection and achievement of relevant plasma drug levels, which involves oral aripiprazole supplementation for the first 21 days with AL initiation.…”