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.

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.

• Authors: 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
• Journal: Journal of child and adolescent psychopharmacology (J Child Adolesc Psychopharmacol) Vol. 25 Issue 3 Pg. 203-12 (Apr 2015) ISSN: 1557-8992 [Electronic] United States
• PMID: 25885010 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Central Nervous System Stimulants
• Risperidone

Topics

• Aggression (drug effects)
• Antipsychotic Agents (administration & dosage, therapeutic use)
• Anxiety Disorders (complications, drug therapy)
• Attention Deficit Disorder with Hyperactivity (complications, drug therapy)
• Attention Deficit and Disruptive Behavior Disorders (complications, drug therapy)
• Central Nervous System Stimulants (administration & dosage, therapeutic use)
• Child
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Male
• Parents (education)
• Risperidone (administration & dosage, therapeutic use)
• Social Behavior
• Treatment Outcome