Comorbid Anxiety and Social Avoidance in Treatment of Severe Childhood Aggression: Response to Adding Risperidone to Stimulant and Parent Training; Mediation of Disruptive Symptom Response

L. Eugene Arnold, Kenneth D. Gadow, Cristan A. Farmer, Robert L. Findling, Oscar Bukstein, Brooke S.G. Molina, Nicole V. Brown, Xiaobai Li, E. Victoria Rundberg-Rivera, Srihari Bangalore, Kristin Buchan-Page, Elizabeth A. Hurt, Robert Rice, Nora K. McNamara, Michael G. Aman

Research output: Contribution to journalArticle

Abstract

Objective: In the four-site Treatment of Severe Childhood Aggression (TOSCA) study, addition of risperidone to stimulant and parent training moderately improved parent-rated disruptive behavior disorder (DBD) symptoms. This secondary study explores outcomes other than DBD and attention-deficit/hyperactivity disorder (ADHD) as measured by the Child and Adolescent Symptom Inventory-4R (CASI-4R). Methods: A total of 168 children ages 6-12 with severe aggression (physical harm), DBD, and ADHD were randomized to parent training plus stimulant plus placebo (basic treatment) or parent training plus stimulant plus risperidone (augmented treatment) for 9 weeks. All received only parent training plus stimulant for the first 3 weeks, then those with room for improvement received a second drug (placebo or risperidone) for 6 weeks. CASI-4R category item means at baseline and week 9 were entered into linear mixed-effects models for repeated measures to evaluate group differences in changes. Mediation of the primary DBD outcome was explored. Results: Parent ratings were nonsignificant with small/negligible effects, but teacher ratings (n=46 with complete data) showed significant augmented treatment advantage for symptoms of anxiety (p=0.013, d=0.71), schizophrenia spectrum (p=0.017, d=0.45), and impairment in these domains (p=0.02, d=0.26), all remaining significant after false discovery rate correction for multiple tests. Improvement in teacher-rated anxiety significantly (p=0.001) mediated the effect of risperidone augmentation on the primary outcome, the Disruptive-total of the parent-rated Nisonger Child Behavior Rating Form. Conclusions: Addition of risperidone to parent training plus stimulant improves not only parent-rated DBD as previously reported, but also teacher-rated anxiety-social avoidance. Improvement in anxiety mediates improvement in DBD, suggesting anxiety-driven fight-or-flight disruptive behavior with aggression, with implications for potential treatment strategies. Clinicians should attend to possible anxiety in children presenting with aggression and DBD. Clinical Trial Registry: Treatment of Severe Childhood Aggression (The TOSCA Study). NCT00796302. clinicaltrials.gov.

Original languageEnglish (US)
Pages (from-to)203-212
Number of pages10
JournalJournal of child and adolescent psychopharmacology
Volume25
Issue number3
DOIs
StatePublished - Apr 1 2015

ASJC Scopus subject areas

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

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    Arnold, L. E., Gadow, K. D., Farmer, C. A., Findling, R. L., Bukstein, O., Molina, B. S. G., Brown, N. V., Li, X., Rundberg-Rivera, E. V., Bangalore, S., Buchan-Page, K., Hurt, E. A., Rice, R., McNamara, N. K., & Aman, M. G. (2015). Comorbid Anxiety and Social Avoidance in Treatment of Severe Childhood Aggression: Response to Adding Risperidone to Stimulant and Parent Training; Mediation of Disruptive Symptom Response. Journal of child and adolescent psychopharmacology, 25(3), 203-212. https://doi.org/10.1089/cap.2014.0104