Paliperidone for irritability in adolescents and young adults with autistic disorder

Psychopharmacology (Berl). 2012 Sep;223(2):237-45. doi: 10.1007/s00213-012-2711-3. Epub 2012 May 3.

Abstract

Rationale: 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.

Objectives: 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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / psychology
  • Child
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Administration Schedule
  • Female
  • Humans
  • Irritable Mood / drug effects*
  • Isoxazoles / administration & dosage
  • Isoxazoles / therapeutic use*
  • Male
  • Paliperidone Palmitate
  • Pilot Projects
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Antipsychotic Agents
  • Isoxazoles
  • Pyrimidines
  • Paliperidone Palmitate