Stepped Pharmacotherapy for Aggressive Youth with ADHD

描述（由申请人提供）：这个指导以患者为导向的研究职业发展奖的目标是促进候选人的进步，走向一个独立的科学事业，专注于治疗策略的青年与严重的破坏性障碍。在第一年干预研究技能的教学和学徒将准备候选人开始一项研究，为有注意力缺陷/多动障碍（ADHD）的攻击性青年进行阶梯式药物治疗。本研究在第2年、第3年和第4年的部分时间进行，将a）为候选人提供对照治疗研究的监督经验，以及B）满足严格试验的迫切需求，以检查联合用药方法是否能改善该患者组的单药治疗结局。儿童期攻击性行为通常与其他破坏性障碍症状一起发展，这些症状与ADHD高度共病。兴奋剂药物是治疗ADHD的一线药物。然而，对于许多接受兴奋剂治疗的儿童来说，攻击性行为和情感不稳定仍然是严重的损害，导致临床医生分层额外的药物，以减少攻击性控制障碍。然而，缺乏证据支持这些儿童的任何药物组合策略是一个很大的问题。这项拟议的研究将首先优化6- 12岁患有ADHD和共病破坏性障碍的攻击性儿童的开放式兴奋剂治疗。ADHD症状受益于兴奋剂治疗但其攻击性持续存在的儿童将在为期8周的双盲试验中随机分配给情绪稳定剂双丙戊酸钠或安慰剂，同时继续进行兴奋剂治疗。所有家庭都将接受结构化的心理社会治疗。该研究将提供初步数据，以进行全面的疗效研究，并通过在第4年提交的R 01提供支持。在整个奖励期间的进一步培训活动将使候选人具备研究技能，并在以下领域提供经验：a）干预试验设计和统计，B）在临床环境中开发和采用治疗策略，包括联合用药和心理治疗，以及c）评估，包括观察和实验室方法，以获得结果和中介测量。导师（N。Schools，P.詹森，V. Kafantaris）和顾问（包括H. Abikoff，P.弗里克，C.格里永，J. Halperin，J. Kane，D. Kolko，S. Pliszka）将提供专家培训和监督。因此，拟议的计划将最终在获奖者的能力，作为一个全面的临床科学家专注于复杂的治疗需求的青年与严重的行为障碍。

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.