Abstract
The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to 6 weeks of double-blind treatment with lurasidone 20 mg/day (N = 50), 60 mg/day (N = 49), or placebo (N = 51). Efficacy measures included the Aberrant Behavior Checklist Irritability subscale (ABC-I, the primary endpoint) and the Clinical Global Impressions, Improvement (CGI-I) scale, and were analyzed using a likelihood-based mixed model for repeated measures. Least squares (LS) mean (standard error [SE]) improvement from baseline to Week 6 in the ABC-I was not significantly different for lurasidone 20 mg/day (-8.8 [1.5]) and lurasidone 60 mg/day (-9.4 [1.4]) versus placebo (-7.5 [1.5]; p = 0.55 and 0.36, respectively). CGI-I scores showed significantly greater LS mean [SE] improvement at Week 6 for lurasidone 20 mg/day versus placebo (2.8 [0.2] vs. 3.4 [0.2]; p = 0.035) but not for lurasidone 60 mg/day (3.1 [0.2]; p = 0.27). Discontinuation rates due to adverse events were: lurasidone 20 mg/day, 4.1%; 60 mg/day, 3.9%; and placebo, 8.2%. Adverse events with an incidence ≥10% (lurasidone combined, placebo) included vomiting (18.0, 4.1%) and somnolence (12.0, 4.1%). Modest changes were observed in weight and selected metabolic parameters. In this study, once-daily, fixed doses of 20 and 60 mg/day of lurasidone were not demonstrated to be efficacious compared to placebo for the short-term treatment of children and adolescents with moderate-to-severe irritability associated with autistic disorder.