In the past two decades, numerous research investigations have demonstrated that children who sustain severe traumatic brain injury (TBI) are a high risk for problems in behavior, adaptive functioning, educational performance, as well as psychiatric disorders. Longitudinal follow-up of children with severe TBI by our group and others has shown that the problems fail to resolve overtime, despite at least partial recovery in cognitive function. Severe TBI leads to chronic social-emotional and behavioral sequelae in adults as well as children, and is associated with persisting family burden and distress. Unfortunately, little is known regarding successful treatment of these sequelae. While some improvement in function has been reported for children with severe TBI placed in-patient rehabilitation programs, the effectiveness of these programs has been challenged on methodological grounds. Drug treatments have been tested, but with mixed results. The purpose of the proposed pilot project is to examine the effects of aripiprazole on the behavioral sequelae of TBI in children. Aripiprazole, although still undergoing clinical trials, is particularly effective in controlling behavioral disinhibition and self-regulatory problems in children with thought and conduct disorders. To determine the effectiveness of this medication in reducing behavior problems and improving school performance in a sample of children who have sustained severe TBI, we will conduct a randomized, placebo controlled, double-blind crossover trial. Children who meet the inclusion criteria will be randomized to a two month regimen of either active medication or placebo, followed by a two month regimen in the crossover arm. At the end of the crossover phase of the study, all children will be given the option of participating in an open label trial during which they will receive aripiprazole for six months. The purpose of the follow-up phase of the study is to determine if the medication effects are sustained with prolonged use. Assessments of behavior, cognitive function, and family status will be carried out prior to treatment, after each of the two crossover treatments, and at the end of the 6-month open label trial. Specific goals are to: (1) determine the effectiveness of aripiprazole in controlling the targeted behavior problems; (2) examine associations of time since injury and other factors as predictors of drug responsiveness and to identify other correlates of efficacy; (3) explore possible medication benefits on other child behavioral and cognitive characteristics are on family functioning; and (4) investigate the extent to which drug effects are sustained during the longer-duration open label trial.
