Olanzapine Versus Placebo in Outpatients with Anorexia Nervosa

描述（由申请人提供）：神经性厌食症（AN）是一种与高发病率和死亡率相关的主要精神疾病。尽管该领域一致认为体重恢复是治疗的优先事项，但AN患者的特定治疗方法没有明确的经验支持。NIMH已将AN确定为需要治疗研究的疾病。 在住院或日间医院治疗的背景下进行的初步研究表明，奥氮平（第二代抗精神病药物）有望治疗AN，可改善体重和相关AN精神病理学。我们最近完成了一项由NIMH支持的奥氮平门诊治疗AN的为期8周的安慰剂对照初步研究。我们的研究结果表明，奥氮平治疗与体重增加、心理状态改善相关，且对低体重患者无不良代谢影响。因此，在本申请中，我们建议在门诊成人AN患者中进行奥氮平与安慰剂的确定性多中心随机双盲安慰剂对照试验。 在该项目中，160名成人AN患者将被随机分配到五个临床中心之一接受奥氮平或安慰剂治疗，共16周-哥伦比亚大学，威尔康奈尔医学院，约翰霍普金斯医疗机构，匹兹堡大学和多伦多大学-所有这些都是众所周知的饮食失调研究和治疗。该研究将确定奥氮平是否比安慰剂更有利于研究参与者实现体重恢复和其他心理改善措施。所有研究参与者将接受定期的“Med-Plus”治疗，包括医疗管理、依从性增强策略和整个药物试验期间的支持性护理。临床管理将包括以下心脏状态和代谢综合征标志物，以确保该人群中与奥氮平相关的任何体重增加不会导致不良临床效应。 迫切需要确定神经性厌食症的有效治疗方法，神经性厌食症是一种恶性疾病，与显著的发病率和死亡率相关，并且没有证据支持的干预措施。如果奥氮平在促进门诊治疗的成人体重增加和心理恢复方面有效，则申请中提出的工作将具有立即的临床效用和显著的公共卫生影响。 公共卫生相关性：神经性厌食症（AN）患者没有经验支持的治疗方法，迫切需要对新治疗方法进行严格的研究。最近发表的报告表明，奥氮平在这一人群中可能有用，来自NIMH支持的治疗开发项目的初步数据表明，奥氮平可能确实是可接受的，可耐受的，并为AN患者提供获益。本研究旨在评估非典型抗精神病药物奥氮平在5个临床中心（哥伦比亚大学、威尔康奈尔医学院、约翰霍普金斯大学、匹兹堡大学和多伦多大学）的成人AN门诊患者大样本中的潜在获益。

DESCRIPTION (provided by applicant): Anorexia Nervosa (AN) is a major mental illness associated with substantial morbidity and mortality. Although there is agreement in the field that weight restoration is a treatment priority, no particular therapeutic approach for patients with AN has clear empirical support. The NIMH has identified AN as an illness in need of treatment research initiatives. Preliminary investigations conducted in the context of inpatient or day hospital treatment have documented that olanzapine, a second generation antipsychotic agent, has promise in the treatment of AN, leading to improvements in body weight and associated AN psychopathology. We recently completed an NIMH-supported 8-week placebo-controlled pilot study of olanzapine in the outpatient treatment of AN. Our results documented that olanzapine treatment was associated with weight gain, improvements in psychological status, and no untoward metabolic effects in low-weight patients. Thus in the present application, we propose to conduct a definitive multi-site randomized double-blind placebo-controlled trial of olanzapine versus placebo in outpatient adults with AN. In this project, 160 adults with AN will be randomly assigned to receive olanzapine or placebo for a total of 16 weeks at one of five clinical sites - Columbia University, Weill Cornell Medical College, Johns Hopkins Medical Institution, University of Pittsburgh and University of Toronto - all well known for the study and treatment of eating disorders. The study will determine whether olanzapine is more beneficial than placebo at achieving weight restoration and other measures of psychological improvement in the study participants. All study participants will receive regular "Med-Plus" treatment sessions that will include medical management, compliance enhancement strategies and supportive care throughout the medication trial. Clinical management will include following cardiac status and markers of metabolic syndrome to assure that any weight gain associated with olanzapine in this population is not causing untoward clinical effects. There is a critical need to identify efficacious treatments for anorexia nervosa, a pernicious disorder that is associated with significant morbidity and mortality, and for which there are no evidence-supported interventions. If olanzapine is useful in promoting weight gain and psychological recovery in adults treated in an outpatient setting, the work proposed in the application will have immediate clinical utility and significant public health impact. PUBLIC HEALTH RELEVANCE: There is no empirically supported treatment for patients with Anorexia Nervosa (AN) and rigorous study of new treatments is sorely needed. Recently published reports have suggested possible utility for olanzapine in this population, and pilot data from an NIMH-supported treatment development project suggest that olanzapine may indeed be acceptable, tolerable and offer benefit to patients with AN. This study aims to measure the potential benefit of the atypical antipsychotic medication olanzapine in a large sample of adult outpatients with AN across five clinical sites - Columbia University, Weill Cornell Medical College, Johns Hopkins, University of Pittsburgh and University of Toronto.