Stepped Pharmacotherapy for Aggressive Youth with ADHD

描述（由申请人提供）：这个以指导患者为导向的研究职业发展奖的目标是促进候选人在专注于严重破坏性障碍青年治疗策略的独立科学事业上取得进展。一年级的教学和干预研究技能培训将为候选人开始一项针对患有注意力缺陷/多动障碍（ADHD）的攻击性青少年的阶梯式药物治疗研究做好准备。本研究在二年级、三年级和四年级的一部分进行，将a)为候选人提供受控治疗研究的监督经验，b)解决严格试验的关键需求，以检查联合用药方法是否比单药治疗能改善该患者组的结果。儿童时期的攻击行为通常与其他破坏性障碍症状一起发展，这些症状与多动症高度共病。兴奋剂药物是多动症的一线治疗方法。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，这导致临床医生在努力减少攻击性控制障碍方面增加了额外的药物。然而，缺乏证据支持这些儿童的任何药物联合策略是一个很大的问题。该研究将首先优化6- 12岁患有多动症和合并症破坏性障碍的攻击性儿童的开放兴奋剂治疗。在为期8周的双盲试验中，那些ADHD症状从兴奋剂治疗中受益但攻击性持续存在的儿童将被随机分配到情绪稳定剂双丙戊酸钠或安慰剂组，同时他们的兴奋剂治疗仍在继续。所有家庭都将接受有组织的心理治疗。该研究将提供初步数据，以进行全面的疗效研究，并在第4年提交R01。在整个奖励期间，进一步的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，包括联合药物治疗和心理社会治疗；c)评估，包括观察和实验室方法，以结果和中介测量。导师（N. Schooler， P. Jensen， V. Kafantaris）和顾问（包括H. Abikoff， P. Frick， C. Grillon， J. Halperin， J. Kane， D. Kolko， S. Pliszka）将提供专家培训和监督。因此，该计划将最终使获奖者成为一名全面的临床科学家，专注于患有严重行为障碍的青少年的复杂治疗需求。

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.