Long-Term Assessment of Lurasidone in Schizophrenia: Post Hoc Analysis of a 12-Month, Double Blind, Active-Controlled Trial and 6-Month Open-Label Extension Study

Abstract

Introduction: A post hoc analysis of a double-blind (DB) active control trial and an open-label extension (OLE) study was conducted to evaluate the long-term effects of lurasidone in patients with schizophrenia.

Methods: In the DB trial, patients were randomised to receive lurasidone or risperidone for 12 months. In OLE, all patients received lurasidone for an additional 6 months. Treatment-emergent adverse events (TEAEs) were evaluated. Efficacy assessments included relapse rate (DB trial only), and Positive and Negative Syndrome Scale, Clinical Global Impression-Severity scale, and Montgomery-Åsberg Depression Rating Scale.

Results: In the DB trial, patients with schizophrenia were randomised to lurasidone (n = 399) and risperidone (n = 190), of whom 129 and 84 continued into OLE, respectively. During the DB trial, incidence of TEAEs was similar for lurasidone (84.1%) and risperidone (84.2%). Lurasidone was associated with minimal changes in metabolic variables and prolactin levels, whereas risperidone was associated with clinically significant increases in prolactin and fasting glucose levels. The proportion of patients with metabolic syndrome was significantly lower in patients treated with lurasidone versus risperidone at the end of the DB trial (25.5% vs 40.4%; p = 0.0177). During OLE, patients switching from risperidone to lurasidone experienced a reduction in weight and prolactin levels; those continuing treatment with lurasidone experienced minimal changes in metabolic variables and prolactin. At the end of OLE, the proportion of patients with metabolic syndrome was no longer significantly different between groups (23.5% vs 31.5%; p = not significant). Efficacy outcomes were generally similar between groups during the DB trial, and were maintained during OLE.

Conclusion: Lurasidone was generally well tolerated and effective in clinically stable schizophrenia patients over the long term. Lurasidone was also generally well tolerated and maintained effectiveness over 6 months in patients switching from risperidone. Patients switching from risperidone experienced improvements in metabolic parameters and prolactin levels. These findings confirm lurasidone's long-term effectiveness and favourable metabolic profile in patients with schizophrenia.

Trial registration: ClinicalTrials.gov identifier NCT00641745.

Keywords: Atypical antipsychotic; Cardiometabolic; Lurasidone; Metabolic syndrome; Prolactin; Risperidone; Schizophrenia; Switch.

Figures

Fig. 1

Disposition of patients with schizophrenia. *Due to a lack of drug supply at study centres in Argentina and Brazil, patients who had not completed the DB trial had the option of enrolling in the OLE study or discontinuing the study. DB double-blind, OLE open-label extension

Fig. 2

Change in prolactin over time from DB baseline to OLE LOCF endpoint, by treatment assignment in DB trial, for (a) males and (b) females. DB double-blind, LOCF last observation carried forward, OLE open-label extension

Fig. 3

Change in percentage of patients with metabolic syndrome (a) from DB baseline to month 12 and (b) from DB baseline to OLE LOCF endpoint, by treatment assignment in Study 237 (safety population). DB double-blind, LOCF last observation carried forward, NS not significant, OLE open-label extension

Fig. 4

Change in weight over time (a) from DB baseline to DB LOCF endpoint and (b) from DB baseline to OLE LOCF endpoint, by treatment assignment in DB trial. DB double-blind, LOCF last observation carried forward, OLE open-label extension

Fig. 5

Kaplan–Meier estimate of the probability of relapse in the DB trial (Study 237) (ITT population). CI confidence interval, DB double-blind, HR hazard ratio, ITT intent-to treat

Fig. 6

Change in PANSS total score over time (a) from DB baseline to DB LOCF endpoint and (b) from DB baseline to OLE LOCF endpoint, by treatment assignment in Study 237 (ITT population). DB double-blind, ITT intent-to treat, LOCF last observation carried forward, OLE open-label extension, PANSS Positive and Negative Syndrome Scale