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: 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
• 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

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：项目描述持续的攻击行为是儿童接受心理健康服务的最常见问题之一，它会增加一生中不利结果的风险。在青春期前，攻击性行为最常在冲动控制缺陷和情感不稳定的背景下发展。大多数受影响的儿童符合破坏性行为障碍的诊断标准，ADHD与之高度共病。刺激性药物是多动症的一线药物疗法，通常还可以改善相关的攻击性和其他行为问题。然而，对于许多接受兴奋剂治疗的儿童来说，攻击性行为和情感波动仍然是严重的损害，导致临床医生使用额外的药物。特别是，为此目的使用抗精神病药和情绪稳定剂的情况急剧增加。然而，目前引用的支持其使用的证据尚未评估其作为ADHD儿童辅助治疗的有效性，这些儿童在充分的兴奋剂治疗后仍具有攻击性。没有数据评估这些药物作为儿童的攻击性是证明难治性兴奋剂单药治疗，其价值的大小作为添加治疗仍然不确定。我们以前发现，51.5%的ADHD和高攻击性儿童在严格的兴奋剂滴定和心理干预后，攻击性行为持续缓解。那些攻击性持续存在的人参加了双丙戊酸钠（DVPX）的对照试验。在随机接受活性DVPX的患者中，52%的人经历了攻击缓解，而服用安慰剂的患者为12%。虽然有意义，但这种临床上的中度效应突出了需要在阶梯设计中确定广泛使用的抗精神病药物治疗是否提供更大的益处。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6-12岁ADHD和ODD/CD儿童攻击性方面的有效性和安全性，这些儿童对兴奋剂治疗和同步行为干预反应不足。在一个开放的兴奋剂滴定和行为治疗的导入后，试验将随机分配攻击性持续存在的儿童接受利培酮或DVPX的连续治疗8周。攻击缓解的儿童将继续他们的方案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）估计了对单独刺激的充分反应率，（2）衡量了DVPX对刺激难治性攻击的影响，（3）定义了可能选择在刺激单药治疗后需要预防性药物治疗的儿童的纳入标准，（4）确定了参与者招募和保留这些研究阶段的可行性。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，益处和责任的知识中令人担忧的空白。通过帮助弥合鸿沟，从目前的药物治疗实践与这一患者群体的相当即兴的特点，从严格的试验概括的指导，这项研究将提供一个重要的贡献，公共卫生。