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: 8136056
• 负责人: MICHAEL George AMAN
• 金额: $ 50.46万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8136056
• 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；品行障碍和对立违抗障碍）构成了一个公共健康问题，基于证据的治疗选择有限。越来越多有攻击行为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相对于更安全的兴奋剂的增量优势。这项双盲、安慰剂对照、平行组研究将比较 (a) 家长行为管理培训 (PMT) + 安慰剂 (PBO)、(b) PMT + d-哌醋甲酯 (d-MPH) 和 ( c) PMT + d-MPH + 利培酮 (RIS) 用于患有严重攻击性、原发性 DBD 和共病 ADHD 的儿童。参与者必须表现出严重身体攻击行为的明确历史和当前模式（即，改良公开攻击量表 (OAS-M)、临床总体印象 (CGI) 量表攻击行为严重程度得分为 4 或更高），在尼松格儿童行为评定表 (NCBRF) 的破坏性总分中获得高分。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类型（反应性与主动性）是否会调节治疗反应。设计：4 个地点（凯斯西储、俄亥俄州立、匹兹堡和石溪）的 216 名儿童将被随机分配到为期 9 周的双盲 PMT + PBO (n=72)、PMT + MPH (n=72) ，或 PMT + MPH + RIS (n=72)。所有小组都将接受为期 12 节的课程，该课程经过仔细监控、基于经验的 PMT。将在 12 周的延长期内对应答者指定的治疗进行跟踪，所有参与者将在基线后一年接受评估。临床变化将通过 (a) 家长对 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 儿童进行访谈； (d) 临床医生 CGI-改进评分 (CGI-I)；以及对孩子与父母行为的直接观察。主要结果指标是 NCBRF 破坏性总分；次要结局是 CGI-I、缓解率（NCBRF 降低至少 25%，加上 CGI-I 评分为 1 或 2）、其他 NCBRF 和 ADHD 症状检查表子量表以及认知测试。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 AE 和耐受性。这项研究将评估安慰剂、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；商品名 Risperdal）在行为治疗背景下的使用情况，并将向参与者的父母进行教授。参与者将是 6 岁至 12 岁（含）的儿童，他们被诊断患有破坏性行为障碍和多动症，并且表现出明显的攻击行为。鉴于我们社会中暴力行为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。