Severely Aggressive Children Receiving Stimulant Medication Versus Stimulant and Risperidone: 12-Month Follow-Up of the TOSCA Trial

Abstract

Objective: The objective of this study was to evaluate 52-week clinical outcomes of children with co-occurring attention-deficit/hyperactivity disorder (ADHD), disruptive behavior disorder, and serious physical aggression who participated in a prospective, longitudinal study that began with a controlled, 9-week clinical trial comparing the relative efficacy of parent training + stimulant medication + placebo (Basic; n = 84) versus parent training + stimulant + risperidone (Augmented; n = 84).

Method: Almost two-thirds (n = 108; 64%) of families in the 9-week study participated in week 52 follow-ups (Basic, n = 55; Augmented, n = 53) and were representative of the initial study sample. The assessment battery included caregiver and clinician ratings and laboratory tests.

Results: Only 43% of participants in the Augmented group and 36% in the Basic group still adhered to their assigned regimen (not significant [NS]); 23% of those in the Augmented group and 11% in the Basic group were taking no medication (NS). Both randomized groups improved baseline to follow-up, but the 3 primary parent-reported behavioral outcomes showed no significant between-group differences. Exploratory analyses indicated that participants in the Augmented group (65%) were more likely (p = .02) to have a Clinical Global Impressions (CGI) severity score of 1 to 3 (i.e., normal to mildly ill) at follow-up than those in the Basic group (42%). Parents rated 45% of children as impaired often or very often from ADHD, noncompliant, or aggressive behavior. The Augmented group had elevated prolactin levels, and the Basic group had decreased weight over time. Findings were generally similar whether groups were defined by randomized assignment or follow-up treatment status.

Conclusion: Both treatment strategies were associated with clinical improvement at follow-up, and primary behavioral outcomes did not differ significantly. Many children evidenced lingering mental health concerns, suggesting the need for additional research into more effective interventions. Clinical trial registration information-Treatment of Severe Childhood Aggression (the TOSCA Study); http://clinicaltrials.gov/; NCT00796302.

Keywords: ADHD; conduct disorder; methylphenidate; oppositional defiant disorder; risperidone.

Figure 1

Consolidated Standards of Reporting Trials (CONSORT) diagram showing participant allocation and attrition. Note: PT = parent training.

Figure 2

Percent of children randomized to basic or augmented with Clinical Global Impression–Severity (CGI-S) scores of 1-3 (normal to mildly ill, non-clinical) and who participated in Week 52 follow-up

Figure 3

Percent of children randomized to basic or augmented who met parent-rated Child and Adolescent Symptom Inventory-4R (CASI-4R) impairment cutoff for either attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), or peer aggression and who participated in Week 52 follow-up.

Figure 4

Weight-by-age adjusted z scores (A) and prolactin levels (B) for consistent basic and augmented treatment.