Moderators, mediators, and other predictors of risperidone response in children with autistic disorder and irritability

L. Eugene Arnold, Cristan Farmer, Helena Chmura Kraemer, Mark Davies, Andrea Witwer, Shirley Chuang, Robert Disilvestro, Christopher J. McDougle, James McCracken, Benedetto Vitiello, Michael G. Aman, Lawrence Scahill, David J. Posey, Naomi B. Swiezy

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Objective/Background: The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology (RUPP) Autism Network found an effect size of d=1.2 in favor of risperidone on the main outcome measure in an 8-week double-blind, placebo-controlled trial for irritability in autistic disorder. This paper explores moderators and mediators of this effect. Method: Intention-to-treat (ITT) analyses were conducted with suspected moderators and mediators entered into the regression equations. MacArthur Foundation Network subgroup guidelines were followed in the evaluation of the results. Results: Only baseline severity moderated treatment response: Higher severity showed greater improvement for risperidone but not for placebo. Weight gain mediated treatment response negatively: Those who gained more weight improved less with risperidone and more with placebo. Compliance correlated with outcome for risperidone but not placebo. Higher dose correlated with worse outcome for placebo, but not risperidone. Of nonspecific predictors, parent education, family income, and low baseline prolactin positively predicted outcome; anxiety, bipolar symptoms, oppositional-defiant symptoms, stereotypy, and hyperactivity negatively predicted outcome. Risperidone moderated the effect of change in 5′-nucleotidase, a marker of zinc status, for which decrease was associated with improvement only with risperidone, not with placebo. Conclusion: The benefit-risk ratio of risperidone is better with greater symptom severity. Risperidone can be individually titrated to optimal dosage for excellent response in the majority of children. Weight gain is not necessary for risperidone benefit and may even detract from it. Socioeconomic advantage, low prolactin, and absence of co-morbid problems nonspecifically predict better outcome. Mineral interactions with risperidone deserve further study.

Original languageEnglish (US)
Pages (from-to)83-93
Number of pages11
JournalJournal of Child and Adolescent Psychopharmacology
Volume20
Issue number2
DOIs
StatePublished - Apr 1 2010

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health
  • Pharmacology (medical)

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    Arnold, L. E., Farmer, C., Kraemer, H. C., Davies, M., Witwer, A., Chuang, S., Disilvestro, R., McDougle, C. J., McCracken, J., Vitiello, B., Aman, M. G., Scahill, L., Posey, D. J., & Swiezy, N. B. (2010). Moderators, mediators, and other predictors of risperidone response in children with autistic disorder and irritability. Journal of Child and Adolescent Psychopharmacology, 20(2), 83-93. https://doi.org/10.1089/cap.2009.0022