Comparative Effectiveness Study for Bipolar Disorder

描述（由申请人提供）：双相情感障碍是一种严重的终身疾病，影响着4.5%的人口——在美国约有1400万人。根据世界卫生组织，双相情感障碍是全球十大最致残的疾病之一。传统上，情绪稳定剂锂（Li）已广泛用于治疗急性情绪发作（躁狂和抑郁）和维持预防复发。然而，近年来，第二代抗精神病药物（SGAs，如喹硫平[QTP]、奥氮平和阿立哌唑）在急性和维持治疗中迅速取代了旧药物。事实上，QTP已经成为治疗双相情感障碍最常用的处方药。这是正确的，尽管观察到SGAs治疗与显著的代谢和潜在的心血管风险相关，因为它们的副作用是体重增加、血脂异常和II型糖尿病。然而，到目前为止，还没有大规模的、随机的比较效果的研究，比较SGA与较老的情绪稳定剂在现实世界中对双相情感障碍的急性或维持治疗中的作用。在现实环境和患者中评估的SGAs与Li等治疗双相情感障碍的较老药物的比较风险和益处代表了具有重大意义的公共卫生问题。因此，本研究的主要目的是评估QTP与Li在双相情感障碍门诊患者中6个月的比较利弊。QTP和Li将与双相情感障碍的其他药物联合使用（辅助个性化治疗[APT]，不包括QTP治疗的锂治疗患者和QTP患者的锂治疗），同时进行典型的临床实践。一个共同的主要目标将是评估随机分配到QTP+APT组和Li+APT组的药物必要临床调整（NCAs）的频率。次要目的是比较QTP+APT与Li+APT在以下方面的效果：未来心血管疾病的风险通过Framingham General cardiovascular risk Score在6个月内的变化来衡量；和2。功能状态。探索性目的将是评估QTP+APT或Li+APT反应的调节因素，包括服务不足的种族和少数民族身份、共病精神和医学疾病、年龄较小（18岁和25岁以下）和年龄较大（55岁）。对QTP+APT或Li+APT有明确纵向反应的参与者的遗传物质也将被收集并发送到NIMH组织库，用于未来的药物基因组学研究。这项研究极有可能对公共卫生产生重大影响，并改变数百万美国双相情感障碍患者的治疗方法。

DESCRIPTION (provided by applicant): Bipolar is a severe and lifelong illness affecting 4.5% of the population - about 14 million people in the U.S. It is one of the top 10 most disabling medical conditions worldwide according to the World Health Organization. Traditionally, the mood stabilizer lithium (Li) has been used extensively for the treatment of acute mood episodes (mania and depression) and for maintenance prevention of relapse. However, in recent years, second generation antipsychotics (SGAs; e.g., quetiapine [QTP], olanzapine, and aripiprazole) have rapidly supplanted older medications for both acute and maintenance treatment. In fact, QTP has become the most commonly prescribed medication for bipolar disorder. This is true in spite of the observation that treatment with SGAs is associated with significant metabolic and, potentially, cardiovascular risk, owing to their adverse effects of weight gain, dyslipidemias, and type II diabetes. To date, however, there have been no large-scale, randomized comparative effectiveness studies comparing SGA's against older mood stabilizers for the acute or maintenance treatment of bipolar disorder in real-world settings. The comparative risks and benefits of SGAs versus older medications such as Li for bipolar disorder assessed in real-world settings and patients represent public health questions of major significance. Therefore, the primary aim of this study is to evaluate comparative benefits and harms for QTP versus Li in bipolar outpatients over a period of 6 months. QTP and Li will be combined with other medications for bipolar disorder (adjunct personalized treatment [APT], excluding QTP for lithium treated patients and lithium for QTP patients) in parallel with typical clinical practice. A co-primary aim will be to assess the frequency of necessary clinical adjustments (NCAs) of medications for the groups randomized to QTP+APT versus Li+APT. Secondary aims will be to compare the effect of QTP+APT versus Li+APT on: 1. The future risk of cardiovascular disease as measured by change in the Framingham General Cardiovascular Risk Score over the course of 6 months; and 2. Functional status. Exploratory aims will be to assess moderators of response to QTP+APT or Li+APT, to include underserved racial and ethnic minority status, comorbid psychiatric and medical disorders, younger (age >18 and <25 years) and older (> 55 years) age. Genetic material will also be collected and sent to the NIMH tissue bank on well-characterized participants with well-defined longitudinal response to QTP+APT or Li+APT for future pharmacogenomic studies. This study has a very high potential to have a major public health impact and to change the treatment of millions of Americans with bipolar disorder. PUBLIC HEALTH RELEVANCE: This study will compare two treatments over 6 months for participants with bipolar disorder who present with at least mild symptoms and who require a change in treatment. The two treatments will be the second generation antipsychotic mood stabilizer quetiapine and the classic mood stabilizer lithium. In addition to quetiapine or lithium, participants can be treated with other medications as needed.