Stepped Pharmacotherapy for Aggressive Youth with ADHD

患有多动症的攻击性青少年的阶梯式药物治疗

基本信息

批准号：
7845036
负责人：
Joseph C Blader
金额：
$ 78.25万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7845036
关键词：
12 year old Acute Adjuvant Adjuvant Analgesic Adjuvant Therapy Adverse effects Affect Affective Aggressive behavior Algorithms Anticonvulsants Antimanic Agents Antipsychotic Agents Attention deficit hyperactivity disorder Behavior Behavior Therapy Behavioral Blinded Child Childhood Chronic Clinical Trials Combination Drug Therapy Communities Conduct Disorder Consensus Data Development Diagnostic Disease Disease remission Disruptive Behavior Disorder Double-Blind Method Enrollment Family Guidelines Healthcare High Prevalence Impairment Intervention Knowledge Life Maintenance Masks Mental Health Mental Health Services Metabolic Mood stabilizers Moods Oppositional Defiant Disorder Outcome Parents Participant Patients Pharmaceutical Preparations Pharmacotherapy Phase Placebos Psychopharmacology Public Health Randomized Refractory Regimen Research Risk Risperidone Safety Sampling School-Age Population Semisodium Valproate Social Development Social Impacts Symptoms Titrations Uncertainty Work Youth abstracting adverse outcome clinically significant control trial design experience high risk improved inclusion criteria partial response primary outcome psychosocial public health relevance response skills treatment response treatment strategy week trial

项目摘要

DESCRIPTION (provided by applicant): Project summary/abstract project summary/Abstract,Part 1: Project Description Persistent aggressive behavior is among the most prevalent problems for which children receive mental health services and it confers heightened risk for unfavorable outcomes throughout life. Among preadolescents, aggressive behavior most often develops in the context of impulse control deficits and affective instability. Most affected children fulfill diagnostic criteria for disruptive behavior disorders, with which ADHD is highly comorbid. Stimulant medication is first-line pharmacotherapy for ADHD and frequently also ameliorates associated aggression and other conduct problems. Yet, for many children receiving stimulant treatment, aggressive behavior and affective volatility remain significant impairments, leading clinicians to layer additional medications. In particular, use of antipsychotics and mood stabilizers for this purpose has risen sharply. Evidence currently cited to support their use, however, has not evaluated their efficacy as adjuvant therapy for children with ADHD whose aggression persists after adequate stimulant treatment. Without data evaluating these agents as adjuncts for children whose aggression is demonstrably refractory to stimulant monotherapy, the magnitude of their value as add-on treatment remains uncertain. We previously found that 51.5% of children with ADHD and high aggression experienced sustained remission of aggressive behavior after rigorous stimulant titration and a psychosocial intervention. Those whose aggression persisted participated in a controlled trial of adjunctive divalproex sodium (DVPX). Of those randomized to active DVPX, 52% experienced remission of aggression, compared to 12% of those who took placebo. While significant, this clinically moderate effect highlights the need to determine in a stepped design if widely-used antipsychotic treatment offers greater benefit. Therefore, we propose to evaluate the efficacy and safety of stimulant+antipsychotic and stimulant+DVPX strategies in ameliorating aggression among 6-12 year-olds with ADHD and ODD/CD who experience inadequate response to stimulant treatment and concurrent behavioral intervention. After an open lead-in of stimulant titration and behavioral therapy, the trial will randomly assign children whose aggression persists to adjunctive treatment with risperidone or DVPX for eight weeks. Children whose aggression remits will continue their regimen for 6 months to examine durability of response and tolerability. The study leverages our prior work that (1) estimated the rate of adequate response to stimulant alone, (2) gauged the effect of DVPX for stimulant-refractory aggression, 3) defined inclusion criteria likely to select children who will need adjunctive medication after stimulant monotherapy, and (4) established the feasibility of participant enrollment and retention through these study phases. Project summary/abstract project summary/Abstract,Part 2: Public Health Relevance Statement The proposed research stands to fill worrisome gaps in our knowledge on the sequencing, benefits, and liabilities of medication treatment strategies for highly impaired children. By helping to bridge the chasm from the rather improvisational character of current pharmacotherapy practice with this patient group to generalizable guidance from rigorous trials, this study will offer an important contribution to public health.

描述（由申请人提供）：项目摘要/摘要项目摘要/摘要，第 1 部分：项目描述持续攻击行为是儿童接受心理健康服务的最普遍问题之一，它会增加一生中出现不利结果的风险。在青春期前的青少年中，攻击性行为最常在冲动控制缺陷和情感不稳定的情况下发生。大多数受影响的儿童都符合破坏性行为障碍的诊断标准，而多动症是高度共病的。兴奋剂药物是治疗多动症的一线药物疗法，通常也可以改善相关的攻击性和其他行为问题。然而，对于许多接受刺激性治疗的儿童来说，攻击性行为和情绪波动仍然会造成严重损害，导致临床医生需要额外服用药物。特别是，为此目的使用抗精神病药物和情绪稳定剂的数量急剧增加。然而，目前引用的支持其使用的证据尚未评估其作为多动症儿童辅助治疗的功效，这些儿童在充分的兴奋剂治疗后攻击行为仍然存在。由于没有数据评估这些药物作为辅助药物治疗那些对刺激性单一疗法明显难以控制攻击行为的儿童，它们作为附加治疗的价值大小仍然不确定。我们之前发现，51.5% 患有 ADHD 和高攻击性的儿童在严格的兴奋剂滴定和心理社会干预后，攻击行为得到持续缓解。那些持续存在攻击行为的人参加了辅助双丙戊酸钠（DVPX）的对照试验。在随机接受主动 DVPX 治疗的患者中，52% 的攻击性得到缓解，而服用安慰剂的患者中这一比例为 12%。虽然很重要，但这种临床上的中等效果凸显了需要在阶梯式设计中确定广泛使用的抗精神病药物治疗是否能提供更大的益处。因此，我们建议评估兴奋剂+抗精神病药和兴奋剂+DVPX策略在改善对兴奋剂治疗和同时行为干预反应不足的6-12岁ADHD和ODD/CD患者的攻击性方面的有效性和安全性。在进行兴奋剂滴定和行为治疗的开放导入后，该试验将随机分配攻击行为持续存在的儿童接受利培酮或 DVPX 辅助治疗，为期八周。攻击行为缓解的儿童将继续接受治疗 6 个月，以检查反应的持久性和耐受性。该研究利用了我们之前的工作：(1) 估计对单独兴奋剂的充分反应率，(2) 衡量 DVPX 对兴奋剂难治性攻击行为的影响，3) 定义可能选择在兴奋剂后需要辅助药物治疗的儿童的纳入标准单一疗法，(4) 确定了这些研究阶段参与者招募和保留的可行性。项目摘要/摘要项目摘要/摘要，第 2 部分：公共卫生相关性声明拟议的研究将填补我们对高度受损儿童药物治疗策略的顺序、益处和责任的认识中令人担忧的空白。通过帮助弥合当前针对该患者群体的药物治疗实践的相当即兴特征与严格试验的普遍指导之间的鸿沟，这项研究将为公共卫生做出重要贡献。