Clinical Implications From the Treatment of Severe Childhood Aggression (TOSCA) Study: A Re-Analysis and Integration of Findings

Abstract

Objective The Treatment of Severe Childhood Aggression (TOSCA) project examined augmentation of stimulant treatment and parent training (PT) with risperidone for severe physical aggression. This article 1) summarizes the clinical implications; 2) re-analyzes the data to examine the utility of four criteria for deciding to augment; and 3) develops a treatment algorithm. Method The newly analyzed four criteria for augmenting comprised failure to attain the following after 3 weeks of stimulant and PT treatment: 1) Clinical Global Impressions-Improvement (CGI-I) of 1 and normal score (≤ 15) on the Nisonger Child Behavior Rating Form Disruptive-Total (D-total); 2) CGI-I of 1 or 2 plus 25% D-Total improvement; 3) a D-Total ≤ 15; and 4) a CGI-Severity of 3 (mild) or better. Effect sizes were calculated. Prior TOSCA publications were reviewed for clinically relevant findings. Results All four criteria resulted in medium or better effect sizes (d=.59–.72) comparing risperidone to placebo. Providing risperidone to children who failed to reach a CGI-I=1 plus D-Total ≤15 resulted in the greatest benefit. Additionally, a review of clinically relevant data suggests that stimulant plus PT shows further improvement after 3 weeks even without augmentation. Conclusion For those children who did not attain a CGI-I of 1 and a D-total score of 15 or below, adding risperidone maximized both the number of children benefitting from treatment and the average amount of benefit. Unless clinical circumstances dictate otherwise, practitioners should delay an antipsychotic for at least a month after optimal stimulant dose is achieved and PT has commenced. Clinical trial registration information Treatment of Severe Childhood Aggression (The TOSCA Study); http://clinicaltrials.gov; NCT00796302.

Narrative Review: Impairing Emotional Outbursts: What They Are and What We Should Do About Them

“…Others needed the addition of divalproex or risperidone to further treat aggression, although children who needed adjunctive medication never improved as much as children on stimulants alone. 68,117 Of the available classes of medications, antipsychotics have been studied the most for reducing aggression and outbursts in the context of psychotic illnesses, 118 bipolar disorder, 118 and autism spectrum and developmental disorders. 119 In the pediatric population, the best evidence currently available for reactive aggression is risperidone.…”

Polypharmacy in the Management of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Review and Update

“…Clinicians should develop sequential plans such as a timeframe for trial discontinuation after improvement or alternative strategies should negative effects be observed. Authors synthesizing data from the TOSCA studies provide specific guidance that risperidone should be discontinued if ineffective, if observed risks outweigh benefits, and even when effective, after 6 months of improved aggression (Barterian et al 2017). Ideally, evidence-based psychosocial interventions are simultaneously implemented that would facilitate stabilization and discontinuation of higher risk medications.…”

Attendance and Engagement in Parent Training Predict Child Behavioral Outcomes in Children Pharmacologically Treated for Attention-Deficit/Hyperactivity Disorder and Severe Aggression

“…The Treatment of Severe Childhood Aggression (TOSCA) study, a multisite, randomized placebo-controlled trial, was conducted to test whether the addition of risperidone (vs. placebo) to ongoing stimulant medication plus parent training (PT) improved behavioral outcomes for seriously aggressive children with ADHD (6-12 years old) (Farmer et al 2011). Findings were that the addition of risperidone resulted in moderately sized improvement in aggressive and disruptive behaviors after 2-4 weeks of treatment (Aman et al 2014;Gadow et al 2016;Barterian et al 2017).…”