Stepped Pharmacotherapy for Aggressive Youth with ADHD

DESCRIPTION (provided by applicant): The goal of this Mentored Patient-Oriented Research Career Development Award is to promote the candidate's progress toward an independent scientific career focused on treatment strategies for youth with severe disruptive disorders. Didactics and apprenticeship in interventions research skills in Year 1 will prepare the candidate to initiate a study of stepped pharmacotherapy for aggressive youth with attention-deficit/hyperactivity disorder (ADHD). This study, conducted in Years 2, 3 and part of 4, will a) provide the candidate with supervised experience in controlled treatment research, and b) address the critical need for rigorous trials to examine if combined medication approaches improve outcomes over monotherapy in this patient group. Childhood aggressive behavior most often develops alongside other disruptive disorder symptoms, which are highly comorbid with ADHD. Stimulant medication is first-line treatment for ADHD. Yet, for many children receiving stimulant treatment, aggressive behavior and affective instability remain significant impairments, leading clinicians to layer additional medications in efforts to diminish aggressive dyscontrol. However, the lack of evidence to support any medication combination strategy for these children is a great concern. The proposed study will first optimize open stimulant treatment for aggressive children 6- 12 years old with ADHD and a comorbid disruptive disorder. Children whose ADHD symptoms benefit from stimulant treatment but whose aggression persists will be randomly assigned to the mood stabilizer divalproex sodium or placebo during an 8-week double-blind trial while their stimulant treatment continues. All families will receive structured psychosocial treatment. The study will furnish preliminary data to enable a full-scale efficacy study, supported through an R01 to be submitted in Year 4. Further training activities throughout the award period will equip the candidate with research skills and provide experience in the areas of: a) intervention trial design and statistics, b) development and adoption in clinical settings of treatment strategies, including combined medication and psychosocial treatment, and c) assessment, including observational and laboratory approaches to outcome and mediator measurement. Mentors (N. Schooler, P. Jensen, V. Kafantaris) and consultants (including H. Abikoff, P. Frick, C. Grillon, J. Halperin, J. Kane, D. Kolko, S. Pliszka) will provide expert training and supervision. The proposed program will therefore culminate in the awardee's competence as a well-rounded clinical scientist focused on the complex treatment needs of youth with severe behavior disorders.