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Moderators, mediators, and other predictors of risperidone response in children with autistic disorder and
L Eugene Arnold1, Cristan Farmer, Helena Chmura Kraemer
1Department of Psychiatry, Ohio State University, Columbus, Ohio, USA.
Insights
Risperidone effectively treats irritability in autistic disorder, with greater benefits for children with higher symptom severity. Factors like weight gain and socioeconomic status influence treatment outcomes.
Area of Science:
- Psychiatry
- Pediatrics
- Pharmacology
Background:
- Irritability is a common challenge in autistic disorder.
- Risperidone demonstrated significant efficacy in a placebo-controlled trial for pediatric irritability.
Purpose of the Study:
- To explore moderators and mediators of risperidone's effect on irritability in autistic disorder.
- To identify factors influencing treatment response and optimize risperidone use.
Main Methods:
- Intention-to-treat (ITT) analyses were performed.
- Moderators and mediators were entered into regression equations.
- Subgroup guidelines from the MacArthur Foundation Network were applied.
Main Results:
- Baseline symptom severity moderated treatment response, with higher severity showing greater improvement with risperidone.
- Weight gain negatively mediated treatment response; higher gain was associated with less improvement with risperidone.
- Parent education, family income, low baseline prolactin, and absence of comorbid symptoms positively predicted outcome.
Conclusions:
- The benefit-risk ratio of risperidone is favorable in more severe cases of irritability in autistic disorder.
- Individual titration of risperidone can lead to excellent outcomes for most children.
- Weight gain is not essential for risperidone efficacy and may be detrimental; further research into mineral interactions is warranted.
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.
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