Olanzapine Versus Placebo in Outpatients with Anorexia Nervosa

描述（由申请人提供）：神经性厌食症（AN）是一种发病率和死亡率很高的主要精神疾病。虽然该领域一致认为体重恢复是治疗的优先事项，但对于AN患者没有特定的治疗方法有明确的经验支持。NIMH已经确定AN是一种需要治疗研究计划的疾病。在住院或日间医院治疗的背景下进行的初步调查表明，第二代抗精神病药物奥氮平在治疗AN方面有希望，可以改善体重和相关的AN精神病理。我们最近完成了一项nimh支持的关于奥氮平在an门诊治疗中的8周安慰剂对照先导研究。我们的研究结果证明，奥氮平治疗与体重增加、心理状态改善有关，并且在低体重患者中没有不良的代谢影响。因此，在目前的申请中，我们建议在门诊成人AN患者中进行奥氮平与安慰剂的多地点随机双盲安慰剂对照试验。在这个项目中，160名患有AN的成年人将被随机分配到五个临床地点之一接受奥氮平或安慰剂共16周-哥伦比亚大学，威尔康奈尔医学院，约翰霍普金斯医学院，匹兹堡大学和多伦多大学-这些都以研究和治疗饮食失调而闻名。该研究将确定奥氮平是否比安慰剂更有利于实现体重恢复和其他心理改善措施的研究参与者。所有研究参与者将接受定期的“Med-Plus”治疗，包括整个药物试验期间的医疗管理、依从性增强策略和支持性护理。临床管理将包括跟踪心脏状态和代谢综合征标志物，以确保该人群中任何与奥氮平相关的体重增加不会引起不良的临床影响。目前迫切需要确定神经性厌食症的有效治疗方法，这是一种与显著发病率和死亡率相关的有害疾病，并且没有证据支持的干预措施。如果奥氮平在促进在门诊治疗的成人体重增加和心理恢复方面是有用的，那么在申请中提出的工作将具有直接的临床效用和显著的公共卫生影响。

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.