The Treatment of Severe Childhood Aggression Study: 12 Weeks of Extended, Blinded Treatment in Clinical Responders.

Objectives: Previous "Treatment of Severe Childhood Aggression" (TOSCA) reports demonstrated that many children with severe physical aggression and attention-deficit/hyperactivity disorder (ADHD) responded well to two randomized treatments (parent training [PT]+stimulant+placebo = Basic vs. PT+stimulant+risperidone = Augmented) for 9 weeks. An important clinical question is whether these favorable outcomes are maintained over longer times.

Methods: Clinical responders to the 9-week trial (n = 103/168), defined as Clinical Global Impressions (CGI)-Improvement of much/very much improved plus substantial reduction in parent ratings of disruptiveness, were followed another 12 weeks (21 weeks total) while remaining on blinded treatment. Outcome measures included Clinical Global Impressions scale, Nisonger Child Behavior Rating Form (NCBRF), other parent/teacher-rated scales, laboratory tests, clinician ratings of abnormal movement, and other adverse events (AEs).

Results: Parent ratings of problem behavior showed minimal worsening of behavior from end of the 9-week acute trial (expected from regression to the mean after selecting best responders), but outcomes at Extension endpoint were meaningfully improved compared with acute study baseline. As expected, outcomes for Basic and Augmented treatment did not differ among these children selected for good clinical response. During Extension, more Augmented subjects had elevated prolactin; there were no clinically confirmed cases of tardive dyskinesia. Delayed sleep onset was the most frequent Basic AE. We also conducted a last-observation-carried-forward analysis, which included both nonresponders and responders. We found that, at the end of Extension, Augmented subjects had more improvement than Basic subjects on the NCBRF Positive Social subscale (p = 0.005; d = 0.44), the Antisocial Behavior Scale Reactive Aggression subscale (p = 0.03; d = 0.36), and marginally so on the Disruptive Behavior Total subscale (p = 0.058; d = 0.29, the primary outcome).

Conclusions: The medium-term outcomes were good for the participants in both treatment groups, perhaps because they were selected for good response. When nonresponders were included in ITT analyses, there was some indication that Augmented surpassed Basic treatment.