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

1/4-兴奋剂和利培酮，用于患有严重身体攻击的青少年

• 批准号: 7879268
• 负责人: MICHAEL George AMAN
• 金额: $ 51.82万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7879268
• 关键词: Adverse event; Affective; Age; Aggressive behavior; Antipsychotic Agents; Attention deficit hyperactivity disorder; Back; Behavior; Behavior Therapy; Child; Child Behavior; Clinical; Cognition; Cognitive; Conduct Disorder; Desire for food; Diagnosis; Disruptive Behavior Disorder; Double-Blind Method; Drops; Educational process of instructing; Electrocardiogram; Ensure; Evidence based treatment; Exhibits; Glucose; Hostility; Hygiene; Interview; Investigation; Lipids; Measures; Methylphenidate; Monitor; Names; Neurologic; Ohio; Oppositional Defiant Disorder; Outcome; Outcome Measure; Parenting behavior; Parents; Participant; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Physical aggression; Placebo Control; Placebos; Procedures; Prolactin; Protocols documentation; Public Health; Published Comment; Randomized; Recording of previous events; Reporting; Risperidone; Safety; Severities; Site; Sleep; Societies; Symptoms; Testing; Time; Training; Violence; Weight; Youth; analog; anti social; atypical antipsychotic; base; compare effectiveness; design; dexmethylphenidate; follow-up; impression; internal control; primary outcome; response; secondary outcome; teacher; treatment effect; treatment response

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.

描述（由申请人提供）：具有严重攻击性的破坏性行为障碍（DBD;行为障碍和对立违抗性障碍）构成了一个公共卫生问题，其循证治疗选择有限。越来越多的具有攻击性的青少年正在接受非典型抗精神病药物治疗，但没有良好的安全性证据或比更安全的兴奋剂更具优势。这项双盲、安慰剂对照、平行组研究将比较（a）父母行为管理培训（PMT）+安慰剂（PBO）、（B）PMT + d-哌甲酯（d-MPH）和（c）PMT + d-MPH +利培酮（RIS）在患有严重攻击性、原发性DBD和共病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历史和当前模式（即，改良显性攻击性量表（OAS-M）的中等或更高分数，临床总体冲动（CGI）量表攻击性严重性分数为4或更高），以及Nisonger儿童行为评定表（NCBRF）的破坏性总分的高分。主要目的是确定（a）PMT + d-MPH是否上级PMT+ PBO和（B）PMT + d-MPH + RIS是否上级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）是否会调节治疗反应。设计图：4个研究中心（凯斯西储、俄亥俄州、匹兹堡和斯托尼布鲁克）的216名儿童将随机接受9周双盲PMT + PBO（n=72）、PMT + MPH（n=72）或PMT + MPH + RIS（n=72）。所有小组都将接受12节课程的仔细监测，以实验为基础的PMT。应答者将在12周的扩展期内接受分配的治疗，所有受试者将在基线后1年接受评估。临床变化将通过以下方式测量：（a）NCBRF & ADHD症状检查表（CL）上的父母评分;（B）ADHD症状检查表上的教师评分;（c）OAS-M儿童的临床医生访谈;（d）临床医生CGI-改善评分（CGI-I）;以及儿童-父母行为的直接观察。主要结局指标是NCBRF破坏性总分;次要结局指标是CGI-I、应答率（NCBRF降低至少25%，加上CGI-I评分1或2）、其他NCBRF和ADHD症状自评量表子量表和认知测试。反社会行为量表的基线评分将评估攻击类型（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-哌甲酯（Focalin）和d-哌甲酯加利培酮（一种非典型抗精神病药物;品牌名称Risperdal）的使用情况，以对抗将教授给参与者父母的行为治疗。参与者将是6至12岁的儿童，他们被诊断患有破坏性行为障碍和ADHD，并表现出明显的攻击性行为。鉴于我们社会中暴力的发生率和严重程度不断增加，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。