Initial severity and efficacy of risperidone in autism: Results from the RUPP trial

Eur Psychiatry. 2016 Feb:32:16-20. doi: 10.1016/j.eurpsy.2015.11.004. Epub 2016 Jan 21.

Abstract

Background: Risperidone is a common psychopharmacological treatment for irritability in autism spectrum disorder (ASD). It is not well-established how effective risperidone is across the initial symptom severity range. This study aims to examine the influence of baseline severity on the efficacy of risperidone in the treatment of ASD.

Methods: Participants were from the NIMH funded RUPP multisite, randomized, double-blind trial that compared risperidone to placebo to treat autistic disorder with severe tantrums, aggression, or self-injury. Participants were aged 5 to 17, and randomly assigned to risperidone (n=49) or placebo (n=52). Baseline and change scores were computed with the Aberrant Behavior Checklist (ABC) parent assessed scales with irritability as the primary outcome, as well as the clinician assessed ABC Irritability subscale, and Clinical Global Impression Scale.

Results: The relationship between baseline severity and change scores for the risperdone and placebo groups was examined with eight competing three-level mixed-effects models for repeated measure models. Significant (P<0.01) interactions between treatment and baseline severity were observed for parent ABC ratings of irritability and lethargy only. Greater magnitudes of the differences between risperidone and placebo were observed from moderate to very severe baseline severity on irritability and lethargy. Initial severity values over approximately 30 had a strong effect on symptom change [irritability: effect size (ES)=1.9, number needed to treat (NNT)=2, lethargy ES=0.9, NNT=5].

Conclusions: Parents may expect benefits of risperidone on irritability and lethargy with moderate to severe symptoms of ASD.

Trial registration: Registry name: ClinicalTrials.gov, trial identifier: NCT00005014, URL: http://www.clinicaltrials.gov/ct2/show/NCT00005014?term=NCT00005014&rank=1, registered on March 31, 2000.

Keywords: Autism; Baseline severity; Clinical trial; Outcome; Placebo; Psychopharmacology.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Aggression / drug effects
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Autistic Disorder / diagnosis
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / psychology
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Drug Monitoring
  • Female
  • Humans
  • Irritable Mood / drug effects
  • Male
  • Risperidone* / administration & dosage
  • Risperidone* / adverse effects
  • Self-Injurious Behavior / drug therapy
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Risperidone

Associated data

  • ClinicalTrials.gov/NCT00005014