Cardiac-Related Mortality with Atypical Antipsychotics

描述（由申请人提供）： 精神分裂症患者死亡率的增加几十年来一直令人关注，已知其死亡率比一般人群高2-3倍。心血管相关事件的死亡被认为在这一人群中更频繁发生，并且可能每年都在上升，这可能是由于更新的第二代抗精神病药物（SGA）。自从引入以来，耐受性更好的SGAs已经相当快地进入一线治疗。然而，随着SGAs使用的增加，沿着出现了许多关于体重增加及其相关后果的文献。这些包括代谢变化，如葡萄糖失调和高脂血症。此外，已知使用氯氮平会发生心肌病、心律失常和心肌炎。为了让政策制定者和临床医生继续倡导和处方这些药物，并让患者继续服用这些昂贵的药物，与SGAs相关的长期治疗应该是有益的，具有成本效益的，最重要的是安全的。这项拟定的研究将确定马里兰州4，436例接受dsperidone或氯氮平治疗的患者的死亡，并纳入氯氮平授权和监测项目数据库或马里兰州抗精神病药物数据库。由社会安全死亡指数确定的所有死亡者的死亡证明将从马里兰州生命记录部门收集。 假设心脏相关死亡在接受氯氮平治疗的患者中发生率更高，因为氯氮平组体重增加、血糖失调和心肌炎的发生率高于利培酮组。还将确定与两种药物相关的心脏相关死亡率的风险因素。此外，这项初步研究将提供必要的基础，以建立一个机制，收集尸检报告和其他重要的临床信息，如心脏病和糖尿病史的病例队列的患者。其他未来计划包括长期随访和对所有已上市的SGA进行比较。本研究将提供抗精神病药物（特别是利培酮和氯氮平治疗的抗精神病药物）导致心脏相关死亡的相对风险的必要信息。这项研究是重要的，因为文献中缺乏非典型抗精神病药物的长期健康结果数据。

DESCRIPTION (provided by applicant): The increased mortality rate of persons with schizophrenia has been of concern for several decades and is known to be 2-3 times higher than the general population. Death from cardiovascular-related events are believed to occur more frequently in this population and may be rising annually possibly due to newer second-generation antipsychotic (SGA) medications. Since their introduction, the more tolerable SGAs have moved fairly quickly into first-line treatment. However, along with the increased use of the SGAs, much literature on weight gain and related consequences has emerged. These include metabolic changes such as glucose dysregulation and hyperlipidemia. Additionally, with clozapine, cardiomyopathy, cardiac arrhythmias, and myocarditis are known to occur. In order for policy makers and clinicians to continue to advocate and prescribe these medications and for patients to continue to take these expensive medications the long-term treatment associated with SGAs should be beneficial, cost-effective and most importantly, safe. This proposed study will identify deaths from a group of 4,436 patients who have been treated with either dsperidone or clozapine in the State of Maryland and included in the Clozapine Authorization and Monitoring Program Database or the Maryland Antipsychotic Database. Death certificates for all who have died, identified by the Social Secudty Death Index, will be collected from the Maryland Division of Vital Records. Cardiac-related deaths are hypothesized to occur more frequently in patients who have been treated with clozapine as weight gain, glucose dysregulation and myocarditis occur more frequently with clozapine than risperidone. Risk factors for cardiac-related mortality associated with both medications will also be determined. Additionally, this preliminary study will provide a necessary foundation to set up a mechanism to collect autopsy reports and additional important clinical information such as cardiac and diabetes history on a case-cohort of patients. Other future plans include longer term follow-up and the comparison of all marketed SGAs. This study will provide needed information on the relative risk of cardiac-related mortality from antipsychotics, specifically those treated with risperidone and clozapine. This study is important as data on long-term health outcomes with atypical antipsychotics is lacking from the literature.