title: Moderators, mediators, and other predictors of risperidone response in children with autistic disorder and irritability.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Ohio State University, Columbus, Ohio, USA.
authors.forename: L Eugene
authors.initials: LE
authors.lastname: Arnold
authors.forename: Cristan
authors.initials: C
authors.lastname: Farmer
authors.forename: Helena Chmura
authors.initials: HC
authors.lastname: Kraemer
authors.forename: Mark
authors.initials: M
authors.lastname: Davies
authors.forename: Andrea
authors.initials: A
authors.lastname: Witwer
authors.forename: Shirley
authors.initials: S
authors.lastname: Chuang
authors.forename: Robert
authors.initials: R
authors.lastname: DiSilvestro
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: McDougle
authors.forename: James
authors.initials: J
authors.lastname: McCracken
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.forename: Michael G
authors.initials: MG
authors.lastname: Aman
authors.forename: Lawrence
authors.initials: L
authors.lastname: Scahill
authors.forename: David J
authors.initials: DJ
authors.lastname: Posey
authors.forename: Naomi B
authors.initials: NB
authors.lastname: Swiezy
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D008297:Male; D055118:Medication Adherence; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D054316:Biomarkers, Pharmacological; D018492:Dopamine Antagonists; D018967:Risperidone