Assessing Outcomes Between Risperidone Microspheres and Paliperidone Palmitate Long-Acting Injectable Antipsychotics Among Veterans
Background: Long-acting injectable antipsychotics (LAIAs) are integral for managing schizophrenia, schizoaffective disorder, and bipolar I disorder among veterans. Studies comparing LAIAs, such as risperidone microspheres and paliperidone palmitate, are limited. The primary objective of our study was to compare the number of psychiatric hospitalizations among veterans initiated on risperidone microspheres and those taking paliperidone palmitate pre- and post-LAIA initiation.
Methods: We included veterans who had received ≥ 2 injections of risperidone microspheres or paliperidone palmitate between January 1, 2016 and December 31, 2018. Nonadherence was defined as missing an injection by > 3 days for risperidone microspheres and > 7 days for paliperidone palmitate. Pre-LAIA and post-LAIA hospitalizations and rehospitalizations were assessed using a pre–post design with equivalent periods. Descriptive statistics were used for demographics and diagnoses. Nonparametric tests were used to analyze primary and secondary outcomes.
Results: The study included 97 veterans; 44 took risperidone microspheres and 53 received paliperidone palmitate. Participants’ average mean (SD) age was 46 (13.8) years, 92% were male, and 94% were diagnosed with schizophrenia or schizoaffective disorder. Veterans administered risperidone microspheres had fewer mean (SD) post-LAIA hospitalizations (0.4 [1.0] vs 0.9 [1.5]; P = .02), were less likely to be rehospitalized (22.7% vs 47.2%; P = .013) and had a shorter mean (SD) treatment duration (41.6 [40.2] vs 58.2 [45.7] weeks; P = .04) compared with paliperidone palmitate.
Conclusion: Veterans receiving risperidone microspheres had fewer posttreatment psychiatric hospitalizations and were less likely to be rehospitalized .
The researchers established reference ranges for risperidone and paliperidone plasma concentrations that represented expected variability within a population and were derived from population pharmacokinetic models.18 Gopal and colleagues conducted a post hoc comparison between paliperidone palmitate and oral risperidone during initiation of long-acting injectable risperidone in patients with acute schizophrenia.19 The researchers found that during the first month after initiating long-acting injectable risperidone, paliperidone palmitate without oral supplementation had similar efficacy and safety to oral risperidone among these patients.19
LAIAs can create a steadier drug plasma concentration compared with oral antipsychotics and do not need to be taken daily. These agents improve adherence by reducing the frequency of medication administrations.20-24 Assessing nonadherence is easier with LAIAs by counting missed injections compared with oral antipsychotics that require calculation of percentage of days covered.25
The results in our study are somewhat unexpected in part because of the close relationship between risperidone and paliperidone. Risperidone is converted to paliperidone (9-OH-risperidone) via hepatic cytochrome P450 2D6. Although the molecules do not have identical pharmacologic profiles, it is accepted that they are similar enough that risperidone can establish oral tolerability when transitioning therapy to paliperidone palmitate and vice versa.24 Although the active moiety in risperidone microspheres and paliperidone palmitate is similar, the dosing interval for risperidone microspheres is 2 weeks compared with 4 weeks with paliperidone palmitate. One potential explanation as to why veterans started on risperidone microspheres experienced better outcomes is because they had twice as many office visits with the health care team. Facility procedures dictate veterans receive the LAIA at an on-site clinic. During the visits, a licensed vocational nurse administers the injection and monitors the patient for 15 to 30 minutes afterward.
Despite new LAIAs coming to market, high-quality data examining potential differences in treatment outcomes among agents are limited. This is problematic for clinicians who want to optimize care by understanding how administration schedules or other aspects of LAIA use could modify treatment outcomes. Our results suggest that an advantage might exist in selecting an agent with a more frequent administration schedule, at least initially. This could allow for close monitoring and regular therapeutic contact, which could improve short-term outcomes. This conclusion is supported by meta-analyses, randomized controlled trials, and conceptual articles conducted by Wehring and colleagues, Berwaerts and colleagues, and Parellada and colleagues, respectively, who examined patients on different LAIAs and contact with health care professionals as part of their research.26-28 These researchers concluded that patients who had regular contact with a health care professional had better outcomes when initiated on a LAIA.26-28
Limitations
There are several limitations in this study. Retrospective and observational methods introduce risks of bias and confounding variables. Sample size might have limited statistical power to detect differences. Veterans might have had undocumented pre- or posthospitalizations at other institutions, which was not accounted for and lack of rehospitalization is not conclusive of a positive outcome. Institutions could improve on our study and help to fill gaps in comparative data by conducting larger analyses over longer periods and including more LAIA agents.
Conclusions
Although veterans that were administered risperidone microspheres had a shorter treatment duration, they were less likely to be rehospitalized, had a fewer mean number of post-LAIA hospitalizations, and had a larger difference in incidence in 100 person-years compared with veterans on paliperidone palmitate. Nonadherence and discontinuation rates were comparable between risperidone microspheres and paliperidone palmitate. Future studies could aim to further clarify differences in outcomes among agents or administration schedules.
