Ling Deng

Efficacy and Safety of Lurasidone in Adolescents with Schizophrenia: A 6-Week, Randomized Placebo-Controlled Study

Abstract Objective: To evaluate the efficacy and safety of lurasidone in acutely symptomatic adolescent patients with schizophrenia. Methods: Patients aged 13–17 years were randomly assigned to 6 weeks of double-blind, fixed-dose lurasidone (40 or 80 mg/day) or placebo. Primary and key secondary efficacy measures were change from baseline to week 6 in the Positive and Negative Symptom Scale (PANSS) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively, using mixed model for repeated measurement (MMRM) analysis. The proportion of patients achieving treatment response at endpoint, based on ≥20% reduction in PANSS total score, was analyzed using a logistic regression model. Results: Least-squares (LS) mean change in PANSS total score from baseline to week 6 was −18.6 with lurasidone 40 mg/day (N = 108; p < 0.001 vs. placebo; effect size = 0.51), −18.3 with lurasidone 80 mg/day (N = 106; p < 0.001 vs. placebo; effect size = 0.48), and −10.5 with placebo (N = 112). Similarly, LS mean change in CGI-S score from baseline to week 6 was significantly greater with lurasidone 40 mg/day (−1.0; p < 0.001; effect size = 0.49) and 80 mg/day (−0.9; p = 0.0015; effect size = 0.45) compared with placebo (−0.5). A significantly higher proportion of patients met responder criteria on lurasidone 40 and 80 mg/day versus placebo (63.9% and 65.1% vs. 42.0%; p < 0.001 for both comparisons). The rate of study discontinuation was 10.3% in lurasidone-treated and 17.7% in placebo-treated patients. The most common adverse events (incidence ≥5% in either lurasidone dose group and at least twice the rate of placebo) for lurasidone 40 mg/day, 80 mg/day, 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%). Treatment with lurasidone was not associated with clinically meaningful effects on body weight, lipids, measures of glycemic control, or prolactin. Conclusions: In this 6-week study, lurasidone at doses of 40 and 80 mg/day demonstrated statistically significant and clinically meaningful symptom improvement in adolescent patients with schizophrenia. Lurasidone was generally well tolerated with few effects on weight and metabolic parameters, consistent with findings in adult patients with schizophrenia.

S73. EFFECT OF LURASIDONE ON COGNITION IN ADOLESCENTS WITH SCHIZOPHRENIA: INTERIM ANALYSIS OF A 2-YEAR OPEN-LABEL EXTENSION STUDY

Abstract Background The onset of schizophrenia typically occurs during adolescence or early adulthood and is characterized by severe symptomatology and lifelong functional impairment. Cognitive dysfunction is common in schizophrenia and is associated with significant impairment in functioning. Very little is known about the long-term effects of antipsychotic treatment on cognition in adolescents with schizophrenia. To this extent, cognitive data are presented from an interim analysis of an ongoing 2-year long-term safety study of lurasidone in the treatment of children and adolescents with schizophrenia. Methods Patients aged 13–17 years with schizophrenia who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL) study in which patients were continued on lurasidone or switched from placebo to lurasidone. Cognitive function was assessed with the Brief CogState battery, which evaluates four cognitive domains: processing speed, attention/vigilance, visual learning, and working memory. Based on normative data, an overall cognitive composite Z-score was calculated as the average of the standardized Z-scores for each of the four cognitive domains. These results are based on an interim analysis of the 2-year data. Results A total of 271 patients completed 6 weeks of double-blind treatment and entered the 2-year extension study. At the time of the interim analysis, 132 patients had completed 52 weeks of treatment (24 patients were 2-year study completers; 96 patients were still ongoing; and 12 patients had discontinued after 52 weeks); 57 patients were still ongoing in the first 1-year of treatment; and 82 patients terminated prior to week 52. The cognitive composite Z-score showed impairment at double-blind baseline (-1.09). Mean change in Z-score, from DB baseline to OL weeks 0 (OL-baseline), 28, 52, and 104, respectively, were observed for the cognitive composite (+0.04, +0.16, +0.30, +0.57), and for the CogState domains processing speed (-0.08, +0.02, +0.16, +0.68), attention/vigilance (0.00, 0.00, +0.05, +0.38), visual learning (+0.19, +0.45, +0.75, +1.07), working memory accuracy (+0.18, +0.24, +0.73, +0.30), working memory speed (+0.06, +0.23, +0.28, +0.15). Discussion In this study of adolescents with schizophrenia, lurasidone was not associated with cognitive impairment after up to 104 weeks of treatment. Larger sample sizes are needed to confirm the robustness of the improvement was observed in selected cognitive domain scores, most notably visual learning and processing speed.