title: Paliperidone for irritability in adolescents and young adults with autistic disorder.
abstract: BACKGROUND
  Individuals with autistic disorder (autism) frequently exhibit significant irritability marked by severe tantrums, aggression, and self-injury. Despite advances in the treatment of this symptom domain in autism, there remains an ongoing need for more effective and better tolerated pharmacotherapies.
  
  
  OBJECTIVE
  The aim of this study is to determine the effectiveness and tolerability of paliperidone for irritability in autism.
  
  
  METHODS
  This is a prospective, 8-week open-label study of paliperidone in 25 adolescents and young adults with autism. Primary outcome measures included the Clinical Global Impressions-Improvement (CGI-I) Scale and the Irritability subscale of the Aberrant Behavior Checklist (ABC-I). Concomitant medications (except antipsychotics) were permitted if dosages were stable for ≥2 months.
  
  
  RESULTS
  Twenty-one (84 %) of 25 subjects ages 12-21 years (mean 15.3 years) responded to paliperidone, based on a CGI-I Scale score of 1 or 2 (very much or much improved) and ≥25 % improvement on the ABC-I. The mean final dosage of paliperidone was 7.1 mg/day (range 3-12 mg/day). Two subjects discontinued paliperidone prior to study completion (moderate sedation, n = 1; nonresponse, n = 1). Mild-to-moderate extrapyramidal symptoms were recorded in four subjects. A mean weight gain of 2.2 ± 2.6 kg (range -3.6 to +7.9 kg) was recorded. Mean age- and sex-normed body mass index increased from 23.6 to 24.2 (p ≤ 0.001). Mean serum prolactin increased from 5.3 to 41.4 ng/mL (p ≤ 0.0001).
  
  
  CONCLUSIONS
  Paliperidone treatment was associated with significant improvement in irritability and was generally well tolerated. Larger scale, placebo-controlled studies are needed to elucidate the efficacy and tolerability of paliperidone in this population.
authors.affiliation: Section of Child and Adolescent Psychiatry, Department of Psychiatry, Indiana University School of Medicine, Christian Sarkine Autism Treatment Center, James Whitcomb Riley Hospital for Children, 705 Riley Hospital Drive, Indianapolis, IN 46202-5200, USA. kstigler@iupui.edu
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Stigler
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Mullett
authors.forename: Craig A
authors.initials: CA
authors.lastname: Erickson
authors.forename: David J
authors.initials: DJ
authors.lastname: Posey
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: McDougle
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001321:Autistic Disorder / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D000068882:Paliperidone Palmitate; D010865:Pilot Projects; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D000068882:Paliperidone Palmitate