Abstract
BackgroundSeveral clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder. This report evaluates preliminary efficacy, safety, tolerability, and pharmacokinetic data for a novel (once-monthly) administration of long-acting injectable risperidone 50 mg in patients with schizophrenia or schizoaffective disorder.MethodsClinically stable patients participated in a 1-year, open-label, single-arm, multicenter pilot study. During the 4-week lead-in phase, patients received long-acting risperidone 50 mg injections every 2 weeks, with 2 weeks of oral risperidone supplementation. Injections of long-acting risperidone 50 mg every 4 weeks followed for up to 48 weeks, without oral supplementation. The primary endpoint was relapse; other assessments included PANSS, CGI-S, adverse event reports, and determination of risperidone and 9-hydroxyrisperidone plasma concentrations.ResultsTwelve patients in the intent-to-treat population (n = 67) met relapse criteria (17.9%). Relapse risk at 1 year was estimated as 22.4%. Non-statistically significant improvements in symptoms (PANSS) and clinical status (CGI-S) at endpoint were observed. The most common adverse events included schizophrenia aggravated not otherwise specified (19.5%), anxiety (16.1%), insomnia (16.1%), and headache (11.5%). There were no unexpected safety and tolerability findings. Mean plasma concentrations for risperidone and 9-hydroxyrisperidone were generally stable during the study.ConclusionOnce-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics), and maintained the clinically stable baseline status of most patients. Although the results suggest that some symptomatically stable patients with schizophrenia or schizoaffective disorder might be safely managed with long-acting risperidone 50 mg once monthly, these findings alone do not identify which patients will have a sufficient therapeutic benefit nor do they quantify comparative effects of standard and altered dosing. Study limitations (the open-label pilot study design, small sample size, and lack of a concurrent biweekly treatment arm) prevent broad interpretations and extrapolations of results. Controlled studies would be required to support a recommendation for alternative dosing regimens.
Highlights
Several clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder
Patients were excluded if they had significant symptom exacerbation in the 8 weeks prior to baseline; were judged by the investigator to be at imminent risk of injury to self, to others, or to property; had a history of substance abuse within the past 6 months or a positive substance test at screening; had impaired hepatic or renal function; were pregnant or breastfeeding; or had received treatment with an oral antipsychotic other than risperidone in the past 8 weeks, depot antipsychotics in the past 6 months, long-acting risperidone in a previous clinical trial, another investigational agent within 30 days, or electroconvulsive therapy within 12 months of baseline
Short- and long-term studies of long-acting risperidone have suggested an optimal population benefit/risk ratio at doses of 25 mg up to 50 mg administered every 2 weeks, the dosing interval for which this product has been approved [4,5,6,7]; there is clinical interest in the possibility of a longer injection schedule, and models derived from single-dose pharmacokinetic data at the 50mg dose suggested that 50 mg every 4 weeks would result in average plasma concentrations similar to those with 25 mg given every 2 weeks, albeit with higher peak-to-trough fluctuations and lower trough levels (Janssen Pharmaceutica, Inc., data on file)
Summary
Several clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder. This report evaluates preliminary efficacy, safety, tolerability, and pharmacokinetic data for a novel (once-monthly) administration of long-acting injectable risperidone 50 mg in patients with schizophrenia or schizoaffective disorder. The first long-acting injectable atypical antipsychotic, long-acting risperidone, has become available and is approved for administration every 2 weeks in patients with schizophrenia. Mean steady-state peak concentrations and peak-trough fluctuations are reduced with long-acting risperidone biweekly dosing compared with daily oral risperidone dosing [2], potentially enabling further clinical improvements with long-acting risperidone related to more predictable and stable drug plasma levels [2,3]
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