ARIPIPRAZOLE IN CHILDREN AND ADOLESCENTS WITH AUTISTIC DISORDER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项关于阿立哌唑治疗自闭症儿童和青少年中常见的干扰行为的有效性、耐受性和安全性的开放标签研究。研究表明，多巴胺和血清素系统的失调导致了自闭症患者的干扰行为。由于典型抗精神病药和非典型抗精神病药的不良反应倾向增加（尽管明显减少），因此仍然需要对这一人群中的青少年进行安全有效的药物治疗。阿立哌唑是多巴胺D2受体的部分激动剂，可被认为是一种多巴胺系统稳定剂。初步研究表明，阿立哌唑对成人受试者有效，最近的研究表明，阿立哌唑对患有品行障碍的青少年没有严重的不良反应。这一证据表明，就有效性和耐受性而言，阿立哌唑可能是自闭症患者的理想化合物。这项为期14周的研究将招募20名患有自闭症的儿童和青少年，受试者将接受5mg/天的阿立哌唑治疗，并有机会在4周的时间内根据患者的耐受性增加到最大剂量15mg。滴定后，受试者将继续服用阿立哌唑维持8周。反应将由主要结果测量的评分来确定：临床总体印象量表(CGI)-改善量表和异常行为检查表（ABC）的易怒子量表。不良反应将通过异常不自主运动量表（AIMS）、辛普森-安格斯评定量表和副作用回顾表进行监测。将对数据进行分析，以初步了解阿立哌唑对儿童和青少年自闭症患者的有效性、耐受性和安全性。这项探索性研究将有助于激发更明确的、可控的研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an open-label study of the effectiveness, tolerability, and safety of aripiprazole for the treatment of interfering behaviors commonly observed in children and adolescents with autistic disorder. Research suggests that a dysregulation of dopamine and serotonin systems contributes to interfering behaviors in autistic individuals. Because of the increased propensity for adverse effects with typical neuroleptics and the atypical antipsychotics (albeit significantly less), there remains a need for a safe and effective pharmacotherapy for youngsters in this population. Aripiprazole, a partial agonist at the dopamine D2 receptor, may be considered a dopamine system stabilizer. Preliminary research demonstrating efficacy in adult subjects, and more recent research of aripiprazole in youngsters with conduct disorder, found no serious adverse effects. This evidence suggests that aripiprazole may be an ideal compound, regarding effectiveness and tolerability, for autistic individuals. The 14-week study will enroll 20 children and adolescents with autism where subjects will receive 5mg/day of aripiprazole, with the opportunity to increase to a maximum dosage of 15 mg over a 4-week period, as tolerated. After titration, subjects will continue on aripiprazole for an 8-week maintenance period. Response will be determined by ratings of primary outcome measures: the Clinical Global Impression Scale (CGI)-Improvement scale and the irritability subscale of the Aberrant Behavior Checklist (ABC). Adverse effects will be monitored with the Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Rating Scale, and the Side Effects Review Form. Data will be analyzed with the intent to gain a preliminary understanding of the effectiveness, tolerability, and safety of aripiprazole in children and adolescents with autism. This exploratory study will serve to stimulate more definitive, controlled research.