Lurasidone for the Treatment of Irritability Associated with Autistic Disorder

• Published in: Journal of autism and developmental disorders Vol. 46; no. 4; pp. 1153 - 1163
• Main Authors: Loebel, Antony, Brams, Matthew, Goldman, Robert S., Silva, Robert, Hernandez, David, Deng, Ling, Mankoski, Raymond, Findling, Robert L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2016; Springer; Springer Nature B.V
• Subjects: Aberrant Behavior Checklist; Adolescent; Adolescents; Analysis; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Attention deficit hyperactivity disorder; Autism; Autism Spectrum Disorders; Autistic adolescents; Autistic Disorder - drug therapy; Behavior Patterns; Behavior Problems; Behavior Rating Scales; Behavioral Science and Psychology; Behaviour disordered adolescents; Care and treatment; Check Lists; Child; Child & adolescent psychiatry; Child and School Psychology; Children; Children & youth; Clinical trials; Comorbidity; Complications and side effects; Critical incidents; Discontinued; Dopamine; Dosage; Drug Therapy; Efficacy; FDA approval; Female; Health aspects; Humans; Impressions; Interpersonal relations; Interpersonal Relationship; Irritability; Irritable Mood; Language Impairments; Least Squares Statistics; Lurasidone; Lurasidone Hydrochloride - administration & dosage; Lurasidone Hydrochloride - adverse effects; Lurasidone Hydrochloride - therapeutic use; Male; Neurobiology; Neurosciences; Original Paper; Outcomes of Treatment; Outpatients; Parameters; Pediatrics; Pervasive Developmental Disorders; Psychiatry; Psychological Patterns; Psychology; Psychotropic drugs; Public Health; Safety; Schizophrenia; Self Destructive Behavior; Self-injury; Short term; Statistical Analysis; Teenagers; Vomiting; United States > US; Autism; Irritability; Lurasidone; Atypical antipsychotic
• ISSN: 0162-3257; 1573-3432
• DOI: 10.1007/s10803-015-2628-x

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.