Olanzapine Versus Placebo in Outpatients with Anorexia Nervosa

描述(申请人提供)：神经性厌食症(AN)是一种主要的精神疾病，与大量的发病率和死亡率有关。尽管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，没有一种特定的治疗方法得到明确的经验支持。NIMH已将AN确定为一种需要治疗研究倡议的疾病。在住院或日间医院治疗方面进行的初步调查证明，第二代抗精神病药物奥氮平在治疗AN方面有希望，导致体重改善和相关的精神病理学。我们最近完成了一项由NIMH支持的为期8周的奥氮平门诊治疗AN的安慰剂对照先导性研究。我们的结果证明，奥氮平治疗与体重增加、心理状态改善有关，对低体重患者没有不良代谢影响。因此，在目前的应用中，我们建议在门诊成人AN患者中进行一项确定的多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治疗总共16周-哥伦比亚大学、威尔·康奈尔医学院、约翰·霍普金斯医学研究所、匹兹堡大学和多伦多大学-所有这些都以研究和治疗进食障碍而闻名。这项研究将确定奥氮平在实现研究参与者体重恢复和其他心理改善措施方面是否比安慰剂更有益。所有研究参与者将在整个药物试验期间接受定期的“Med-Plus”治疗，其中将包括医疗管理、顺应性增强战略和支持性护理。临床治疗将包括跟踪心脏状态和代谢综合征的标志物，以确保该人群中与奥氮平相关的任何体重增加都不会导致不良的临床效果。迫切需要确定有效的治疗神经性厌食症的方法，这是一种与严重的发病率和死亡率有关的有害疾病，而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年人的体重增加和心理恢复方面是有效的，申请中提出的工作将立即具有临床实用价值和重大的公共卫生影响。

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.