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.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and the presence of restricted, repetitive patterns of behavior, interests, or activities
Greater improvement was observed at endpoint on the CGI-I scale for the lurasidone 20 mg/day group compared with the placebo group
Abnormal serotonergic and/or dopaminergic neurotransmission has been hypothesized to be related to this constellation of behaviors, which suggests a potential therapeutic role for atypical antipsychotics (Lesch and Merschdorf 2000; Moore et al 2002; Siever 2008; Seo et al 2008; Callesen et al 2013; Duke et al 2013; Kolevzon et al 2014)
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and the presence of restricted, repetitive patterns of behavior, interests, or activities. Moderate to severe symptoms of irritability (broadly defined to include tantrums, aggression, self-injurious behavior, and quickly changing moods) have been observed in about a quarter of subjects in various studies (Hill et al 2014; Lecavalier 2006). These maladaptive behaviors can interfere with everyday activities, cause substantial caregiver stress, and may have a negative impact on long-term prognosis (Bradley et al 2004; Eisenhower et al 2005; Murphy et al 2005; Lecavalier et al 2006; Volkmar et al 1999). Aggressive or self-injurious behavior is associated with an increased risk
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