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

• 批准号: 8476726
• 负责人: Joseph C Blader
• 金额: $ 24.62万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8476726
• 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; Lead; 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

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：项目描述持续的侵略行为是儿童获得心理健康服务的最普遍的问题，并且使一生中不利的结果的风险更高。在挑选前量中，侵略性行为通常是在冲动控制缺陷和情感不稳定的背景下发展的。大多数受影响的儿童符合破坏性行为障碍的诊断标准，而ADHD高度合并。刺激性药物是多动症的一线药物疗法，并且经常减轻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，侵略性行为和情感波动率仍然很大，导致临床医生能够分层其他药物。特别是，使用抗精神病药和情绪稳定器为此目的急剧上升。然而，目前被引用以支持其使用的证据尚未评估其作为辅助治疗的疗效，该治疗对ADHD儿童的辅助治疗后，其侵略性在适当的刺激治疗后仍存在。没有将这些药物评估为侵略性对刺激性单一疗法难治的儿童的辅助手段的情况，其价值的大小仍然不确定。我们先前发现，在严格的刺激滴定和社会心理干预后，有51.5％的多动症和高侵略性儿童持续缓解了侵略行为。那些侵略性持续存在的人参与了辅助divalproex钠（DVPX）的对照试验。在那些随机到活跃DVPX的人中，有52％的人经历了侵略性的缓解，而安慰剂的人中有12％。尽管很重要，但这种临床中等的影响强调了在阶梯设计中确定是否有必要，如果广泛使用的抗精神病药能够提供更大的好处。因此，我们建议评估刺激性+抗精神病药和兴奋剂+DVPX策略在6-12岁的ADHD和ODD/CD之间的侵略性方面的疗效和安全性，而对兴奋剂治疗的反应不足和一致的行为干预。在开放刺激性滴定和行为疗法的开放率后，该试验将随机分配侵略性的儿童，其侵略性持续到利培酮或DVPX辅助治疗八周。侵略性降低的儿童将继续他们的方案6个月，以检查反应和耐受性的持久性。这项研究利用了我们先前的工作，（1）估计单独刺激剂的适当反应率，（2）衡量DVPX对刺激性侵略侵略的影响，3）定义的纳入标准可能选择可能需要刺激性单层疗法后需要辅助药物的儿童，并通过刺激性单层疗法以及（4）通过这些参与者的入学率进行了研究和重新研究。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旨在填补我们对高度受损儿童的药物治疗策略的测序，福利和责任的知识中的令人担忧的差距。通过帮助从该患者组的当前药物治疗实践的即兴特征到严格试验的可推广指导，这项研究将为公共卫生提供重要贡献。