1/4-Stimulant and Risperidone for Youth with Severe Physical Aggression

描述（由申请人提供）：破坏性行为障碍（dbd；行为障碍和对立违抗障碍）与严重的攻击构成了一个公共卫生问题，基于证据的治疗方案是有限的。越来越多的具有攻击性的青少年正在接受非典型抗精神病药物的治疗，但没有充分的证据表明其安全性或比更安全的兴奋剂有更大的优势。这项双盲、安慰剂对照、平行组研究将比较(a)父母行为管理训练(PMT) +安慰剂（PBO）， (b) PMT + d-哌醋甲酯（d-MPH），以及(c) PMT + d-MPH +利培酮（RIS）在患有严重攻击、原发性dbd和共病性ADHD的儿童中的有效性。参与者必须表现出明确的严重身体攻击的历史和当前模式（即，修改显性攻击量表（OAS-M）的中等或更高分数，临床总体印象（CGI）量表严重程度得分为4或更高），并且在nisongger儿童行为评定表（NCBRF）的破坏性总分中得分较高。主要目的是确定(a) PMT+ d-MPH是否优于PMT+ PBO，以及(b) PMT+ d-MPH + RIS是否优于PMT+ d-MPH和PMT+ PBO。次要目的包括确定攻击类型（反应性与主动性）是否调节治疗反应。设计：来自4个地点（凯斯西储、俄亥俄州立、匹兹堡和石溪）的216名儿童将被随机分为PMT + PBO （n=72）、PMT + MPH （n=72）或PMT + MPH + RIS （n=72）的9周双盲组。所有的小组都将接受12节精心监控的、基于经验的PMT课程。应答者将在12周的延长期内接受其指定的治疗，所有参与者将在基线后一年进行评估。临床变化将通过(a)父母对NCBRF和ADHD症状检查表（CL）的评分来衡量；(b)教师对ADHD症状CL的评分；(c)临床医生对OAS-M患儿的访谈；(d)临床cgi -改善评分（CGI-I）；以及对亲子行为的直接观察。主要结果测量是NCBRF破坏性总分；次要结局是CGI-I，反应率（NCBRF减少至少25%，加上CGI-I得分为1或2），其他NCBRF和ADHD症状检查表亚量表，以及认知测试。反社会行为量表的基线得分将评估攻击类型（反应性或主动性）作为潜在的调节因素。还将评估ae和耐受性。本研究将评估安慰剂、d-哌醋甲酯（福卡林）和d-哌醋甲酯加利培酮（一种非典型抗精神病药物；品牌名利培酮）与行为疗法的使用情况，这些疗法将教给参与者的父母。参与者将是6至12岁（含12岁）的儿童，他们被诊断患有破坏性行为障碍和多动症，并表现出明显的攻击行为。鉴于我们社会中暴力事件的发生率和严重性不断上升，这项调查将有助于确定药物治疗与家长提供的行为治疗相结合是否能减少儿童的攻击性。

DESCRIPTION (provided by applicant): Disruptive behavior disorders (DBDs; conduct disorder and oppositional-defiant disorder) with severe aggression constitute a public health problem for which evidence-based treatment options are limited. Increasing numbers of youth with aggression are being treated with atypical antipsychotics without good evidence of safety or incremental advantage over safer stimulants. This double-blind, placebo-controlled, parallel groups study will compare the effectiveness of (a) parent training in behavior management (PMT) + placebo (PBO), (b) PMT + d-methylphenidate (d-MPH), and (c) PMT + d-MPH + risperidone (RIS) in children with severe aggression, primary DBDs, and comorbid ADHD. Participants must exhibit a clear history and current pattern of serious physical aggression (i.e., moderate or higher scores on the Modified Overt Aggression Scale (OAS-M), a Clinical Global Impressions (CGI) Scale Severity score of 4 or higher for aggression), and high scores on the on the Disruptive-Total of the Nisonger Child Behavior Rating Form (NCBRF) . The primary aims are to determine (a) if PMT + d-MPH are superior to PMT+ PBO and (b) if PMT + d-MPH + RIS are superior to PMT + d-MPH and to PMT + PBO. Secondary aims include determining whether type of aggression (reactive vs. proactive) moderates treatment response. Design: Two hundred sixteen children across 4 sites (Case Western Reserve, Ohio State, Pittsburgh, & Stony Brook) will be randomized to 9 weeks double-blind of PMT + PBO (n=72), PMT + MPH (n=72), or PMT + MPH + RIS (n=72). All groups will receive a 12-session course of carefully monitored, empirically-based PMT. Responders will be followed on their assigned treatments in a 12-week Extension, and all participants will be assessed at one year after baseline. Clinical change will be measured by (a) parent ratings on the NCBRF & ADHD Symptom Checklist (CL) ; (b) teacher ratings on the ADHD Symptom CL; (c) clinician interview of the child with OAS-M; (d) clinician CGI-Improvement score (CGI-I); and direct observations of child-parent behavior. The primary outcome measure is the NCBRF Disruptive Total score; secondary outcomes are CGI-I, response rate (NCBRF reduction of at least 25%, plus CGI-I score of 1 or 2), other NCBRF and ADHD Symptom Checklist subscales, and cognitive tests. Baseline score on the Antisocial Behavior Scale will assess type of aggression (reactive or proactive) as a potential moderator. AEs and tolerability will also be assessed. This study will assess the use of placebo, d-methylphenidate (Focalin), and d-methylphenidate plus risperidone (an atypical antipsychotic drug; brand name Risperdal) against the back-drop of behavior therapy which will be taught to the parents of participants. The participants will be children ages 6 to 12 years, inclusive, who have been diagnosed with a disruptive behavior disorder plus ADHD and who display significant aggressive behavior. Given the increasing rates and severity of violence in our society, this investigation will help to determine if drug therapy, combined with parent-provided behavior therapy, can reduce child aggression.