Stepped Pharmacotherapy for Aggressive Youth with ADHD

描述(由申请者提供)：这个以患者为导向的导师研究职业发展奖的目标是促进候选人在独立的科学职业生涯中取得进展，专注于治疗患有严重破坏性障碍的青少年的策略。第一年的干预研究技能的教学和学徒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)的攻击性青年的阶梯药物疗法的研究做好准备。这项研究在第二年、第三年和第四年进行，将a)为候选人提供受控治疗研究的监督经验，以及b)解决严格试验的迫切需要，以检验在这一患者组中，联合用药方法是否比单一治疗方法改善结果。儿童时期的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高度共存。兴奋剂是ADHD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障碍，导致临床医生分层服用额外的药物，以努力减少攻击性失控。然而，缺乏证据支持针对这些儿童的任何药物联合策略是一个非常令人担忧的问题。这项拟议的研究将首先优化对患有ADHD和共病干扰障碍的6-12岁攻击性儿童的开放刺激治疗。在一项为期8周的双盲试验中，ADHD症状受益于兴奋剂治疗但攻击性持续存在的儿童将被随机分配到情绪稳定剂异丙丙酮钠或安慰剂，同时继续接受兴奋剂治疗。所有家庭都将接受系统的心理社会治疗。这项研究将提供初步数据，以支持通过将在第四年提交的R01进行的全面疗效研究。整个获奖期内的进一步培训活动将使候选人掌握研究技能，并在以下领域提供经验：a)干预试验设计和统计，b)在临床环境中制定和采用治疗策略，包括药物和心理社会治疗的综合治疗，以及c)评估，包括结果和介体测量的观察性和实验室方法。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，拟议的计划将使获奖者成为一名全面发展的临床科学家，专注于患有严重行为障碍的青年的复杂治疗需求。

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.