A 6-week, double-blind, placebo- and haloperidol-controlled, phase II study of lurasidone in patients with acute schizophrenia

Abstract

Objective: The objective of this study was to evaluate the short-term efficacy and safety of the atypical antipsychotic agent lurasidone in the treatment of schizophrenia. Methods: In this phase II, randomized, double-blind, placebo-controlled study, hospitalized adult patients diagnosed with schizophrenia and experiencing an acute exacerbation of psychotic symptoms were randomly assigned to 6 weeks of fixed-dose lurasidone 20 mg/day ( n = 71), lurasidone 40 mg/day ( n = 67), lurasidone 80 mg/day ( n = 71), haloperidol 10 mg/day ( n = 72, included to test for assay sensitivity), or placebo ( n = 72). Efficacy was assessed using the brief psychiatric rating scale, positive and negative syndrome scale, and clinical global impression-severity. Safety assessments included incidence of adverse events and clinical laboratory measures. Results: Numerical improvement was observed from baseline to week 6 (last observation carried forward) on all efficacy measures in all treatment groups; however, no statistically significant differences were noted between any lurasidone group and placebo, or between haloperidol and placebo. The most common adverse events in lurasidone-treated patients, with an incidence of at least 10% (dose groups combined) and greater than placebo, were sedation (15.3%), dyspepsia (13.4%), nausea (13.4%), akathisia (12.4%), and vomiting (10.5%); for haloperidol, the most common adverse events (incidence ⩾ 10% and greater than placebo) were extrapyramidal disorder (20.8%), sedation (19.4%), akathisia (19.4%), dystonia (15.3%), insomnia (13.9%), and somnolence (12.5%). Lurasidone was associated with minimal changes in weight, metabolic parameters, and prolactin levels. Conclusions: None of the lurasidone groups separated from placebo in this clinical study of patients with acute schizophrenia. In addition, haloperidol, which was included for assay sensitivity, did not separate from placebo, resulting in a failed study. Possible reasons for the lack of assay sensitivity in this study include the use of multiple active treatment arms and the relatively large placebo response. Consistent with other studies, lurasidone was generally safe and well tolerated, with minimal effects on weight or metabolic parameters.