title: Lurasidone for the Treatment of Irritability Associated with Autistic Disorder.
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.
authors.affiliation: Sunovion Pharmaceuticals, Inc., Fort Lee, NJ, USA.
authors.forename: Antony
authors.initials: A
authors.lastname: Loebel
authors.affiliation: Menninger Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brams
authors.affiliation: Sunovion Pharmaceuticals, Inc., Fort Lee, NJ, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Goldman
authors.affiliation: Sunovion Pharmaceuticals, Inc., Fort Lee, NJ, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Silva
authors.affiliation: Sunovion Pharmaceuticals, Inc., Fort Lee, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hernandez
authors.affiliation: Sunovion Pharmaceuticals, Inc., Fort Lee, NJ, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Deng
authors.affiliation: Sunovion Pharmaceuticals, Inc., Fort Lee, NJ, USA. Raymond.Mankoski@Sunovion.com.|Sunovion Pharmaceuticals, Inc., 84 Waterford Drive, Marlborough, MA, 01752, USA. Raymond.Mankoski@Sunovion.com.
authors.forename: Raymond
authors.initials: R
authors.lastname: Mankoski
authors.affiliation: Child and Adolescent Psychiatry, Kennedy Krieger Institute and Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001321:Autistic Disorder / Q000188:drug therapy*; D002648:Child; D005260:Female; D006801:Humans; D007508:Irritable Mood; D000069056:Lurasidone Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male
chemical_list: D014150:Antipsychotic Agents; D000069056:Lurasidone Hydrochloride
keywords: Atypical antipsychotic; Autism; Irritability; Lurasidone