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.

Keywords: adolescent; clinical study; lurasidone; schizophrenia; treatment.

FIG. 1.

Patient disposition for adolescents with schizophrenia enrolled in a 6-week, randomized, double-blind placebo-controlled study of lurasidone.

FIG. 2.

Least-squares mean change in (A) PANSS total score^a and (B) CGI-S score^b from baseline through week 6 in adolescents with schizophrenia treated with lurasidone 40 mg/day, lurasidone 80 mg/day, or placebo (MMRM analysis, ITT population). ^aMean (SD) scores at baseline were 94.5 (11.0), 94.0 (11.1), and 92.8 (11.1) for the lurasidone 40 mg/day, lurasidone 80 mg/day, and placebo groups, respectively. ^bMean (SD) scores at baseline were 4.9 (0.6), 4.8 (0.7), and 4.8 (0.6) for the lurasidone 40 mg/day, lurasidone 80 mg/day, and placebo groups, respectively. *p < 0.05; ^†p < 0.01; ^‡p < 0.001 versus placebo. CGI-S, Clinical Global Impressions-Severity; ITT, intent-to-treat; MMRM, mixed model for repeated measurement; PANSS, Positive and Negative Syndrome Scale; SD, standard deviation.