SA114. Lurasidone for the Treatment of Adolescent Patients With Schizophrenia: Effect on PANSS Subscales

Abstract

Background: Lurasidone is an atypical antipsychotic agent that has demonstrated efficacy in the treatment of adults with schizophrenia in the dose range of 40–160 mg/d. The objective of this randomized, double-blind, placebo-controlled study was to evaluate the acute efficacy and safety of lurasidone in adolescent patients with schizophrenia. Methods: Adolescents (13–17 years old) diagnosed with schizophrenia were randomly assigned to 6 weeks of double-blind treatment with fixed-dose lurasidone 40 mg/d, 80 mg/d, or placebo. Changes from baseline to Week 6 in PANSS total and subscale (positive, negative, general psychopathology, excitability) scores were evaluated using mixed-model, repeated-measures analysis. Treatment response was defined as ≥20% reduction from baseline in PANSS total score at Week 6 and was analyzed using a logistic regression model with last observation carried forward (LOCF) approach. Results: A total of 326 patients (mean age, 15.4 years) were randomized and received lurasidone 40 mg/d (N = 108), 80 mg/d (N = 106), or placebo (N = 112). The PANSS total score at Week 6 demonstrated a placebo-adjusted, least-squares (LS) mean improvement of −8.0 (P < .001; effect size [ES] = 0.51) for the 40 mg/d group and −7.7 (P < .001; ES = 0.48) for the 80 mg/d group. Placebo-adjusted LS mean change for lurasidone 40 mg/d and 80 mg/d, respectively, was −3.2 (P < .001; ES = 0.62) and −3.2 (P < .001; ES = 0.60) on the PANSS positive subscale, −1.7 (P = .011; ES = 0.41) and −1.6 (P = .022; ES = 0.35) on the PANSS negative subscale, −2.8 (P = .012; ES = 0.38) and −2.8 (P = 0.011; ES = 0.37) on the PANSS general psychopathology subscale, and −1.1 (P = .016; ES = 0.36) and −1.8 (P < .001; ES = 0.53) on the PANSS excitability subscale. The proportion of treatment responders at Week 6 (LOCF) was 42.0% in the placebo group, 63.9% in the lurasidone 40 mg/d group (P < .001; NNT = 5), and 65.1% in the lurasidone 80 mg/d group (P < .001; NNT = 5). The most common adverse events (incidence ≥5% in either lurasidone group and at least twice the rate of placebo) for lurasidone 40 mg/d, 80 mg/d, and placebo, respectively, were nausea (12.7%, 14.4%, and 2.7%), somnolence (9.1%, 11.5%, and 5.4%), akathisia (9.1%, 8.7%, and 1.8%), vomiting (8.2%, 6.7%, and 1.8%), and sedation (5.5%, 1.9%, and 1.8%). The rate of study discontinuation due to adverse events was higher in placebo-treated versus lurasidone-treated patients (8.0% vs. 3.7%, respectively). Conclusion: In this double-blind, placebo-controlled study of adolescent patients with schizophrenia, lurasidone (40 mg/d and 80 mg/d) demonstrated statistically significant efficacy and clinically meaningful improvement across a range of symptoms associated with this disorder. Lurasidone treatment was generally safe and well tolerated in this study. Sponsored by Sunovion Pharmaceuticals Inc. ClinicalTrials.gov identifier: {type:clinical-trial,attrs:{text:NCT01911429,term_id:NCT01911429}}NCT01911429