Initiating Aripiprazole Lauroxil: Post Hoc Analysis of Safety and Tolerability of 1-Day and 21-Day Regimens

Abstract

Objective: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic, has 2 initiation options: 1-day (AL NanoCrystal Dispersion [AL_NCD] injection plus 30 mg oral aripiprazole on day 1 only) and 21-day (15 mg oral aripiprazole for 21 days). This post hoc analysis assessed the safety and tolerability of both initiation approaches.

Methods: We analyzed data from the first 4 weeks of 2 AL studies, one using the 1-day initiation regimen (conducted between November 2017 and March 2019) and the other using the 21-day initiation regimen (conducted between December 2011 and March 2014). Outcomes of interest during the matched 4-week period included the likelihood of adverse events (AEs), including those associated with discontinuation, rated as serious, or of special interest (injection site reactions [ISRs] and akathisia).

Results: The 1-day (n = 99) and 21-day (n = 415) initiation regimens had comparable rates of AEs (57.6% and 52.0%, respectively; most were mild), serious AEs (2.0% and 1.4%), and AEs leading to discontinuation (4.0% and 3.1%). The incidence of ISRs was 11.1% after the AL_NCD injection (day 1) in the 1-day initiation regimen. ISR rates for the AL starting doses were 9.2% for the 1-day regimen (AL 1064 mg on day 8) and 3.9% for the 21-day regimen (AL 441 mg/882 mg on day 1). Rates of akathisia were 9.1% and 11.1% for the 1-day and 21-day regimens, respectively. One patient discontinued because of an ISR in the 21-day study, and 2 patients in the 21-day study discontinued because of akathisia. Mean changes from baseline in week 4 Positive and Negative Syndrome Scale total scores were −17.4 (1-day) and −19.5 (21-day).

Conclusions: Four-week safety and tolerability were similar following the initiation of AL with either the 1-day or 21-day regimen, supporting the utility of both initiation regimens. Engaging patients in discussions regarding options for initiating AL may help facilitate shared decision-making and personalization of treatment for patients with schizophrenia.

Trial Registration: ClinicalTrials.gov identifiers: NCT03345979 and NCT01469039

J Clin Psychiatry 2024;85(3):23m15132

Author affiliations are listed at the end of this article.

Plain Language Summary

Patients with schizophrenia can start treatment with the long-acting injectable medication aripiprazole lauroxil (or AL) using either a 1-day or 21-day initiation regimen with their first dose of AL.

The 1-day approach was designed to provide the same drug concentrations as the 21-day regimen, but clinicians often ask whether the two approaches are equally safe.

We looked at the safety of the two initiation methods in separate studies and found that the numbers of people who had side effects were similar and most side effects were mild in both studies.

These results tell us that patients with schizophrenia and their doctors can choose between two ways of safely starting AL, either a 1-day initiation regimen or a 21-day initiation regimen.