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；品行障碍和对抗-违抗障碍)具有严重的攻击性，构成了一个公共卫生问题，其循证治疗选择有限。越来越多的有攻击性的年轻人正在接受非典型抗精神病药物的治疗，但没有很好的证据表明安全或比更安全的兴奋剂更具优势。这项双盲、安慰剂对照、平行分组研究将比较(A)父母行为管理(PMT)+安慰剂(PBO)、(B)PMT+d-哌醋甲酯(d-MPH)和(C)PMT+d-MPH+利培酮(RIS)在患有严重攻击性、原发DBDS和合并ADHD的儿童中的有效性。参与者必须表现出明确的身体攻击历史和当前模式(即，修改后的公开攻击量表(OAS-M)得分中等或更高，临床总体印象(CGI)严重程度得分为4或更高)，以及尼松格儿童行为评定表(NCBRF)的破坏性-总分(NCBRF)得分高。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。次要目标包括确定攻击性类型(反应性与主动性)是否缓和治疗反应。设计：四个地点(凯斯西部保护区、俄亥俄州立大学、匹兹堡和石溪)的216名儿童将随机分为PMT+PBO(n=72)、PMT+MPH(n=72)或PMT+MPH+RIS(n=72)组。所有小组都将接受为期12个疗程的严密监测、以经验为基础的PMT。应答者将在12周内接受分配给他们的治疗，所有参与者将在基线后一年接受评估。临床变化将通过(A)NCBRF和ADHD症状清单(CL)上的父母评分；(B)ADHD症状CL上的教师评分；(C)OAS-M对儿童的临床医生访谈；(D)临床医生CGI-改善评分(CGI-I)；以及对儿童-父母行为的直接观察。主要结果是NCBRF破坏性总分；次要结果是CGI-I、反应率(NCBRF减少至少25%，加上CGI-I评分1或2)、其他NCBRF和ADHD症状检查表分量表，以及认知测试。反社会行为量表的基线分数将评估攻击类型(反应性或主动性)，作为潜在的调节因素。还将评估AES和耐受性。这项研究将评估安慰剂、D-哌醋甲酯(福卡林)和d-甲酯加利培酮(一种非典型的抗精神病药物；品牌名利培酮)的使用情况，以对抗行为治疗的背景，该治疗将被教授给参与者的父母。参与者将是年龄在6岁到12岁之间的儿童，他们被诊断出患有破坏性行为障碍和ADHD，并表现出显著的攻击性行为。鉴于我们社会中暴力的发生率和严重性不断增加，这项调查将有助于确定药物治疗与父母提供的行为治疗相结合是否可以减少儿童的攻击性。

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.