Clinical Impact of Unstable AED Levels in Elderly Nursing Home Epilepsy Patients

描述(申请人提供)：尽管苯妥英(PHT)被认为是老年人跌倒的原因，并且由于复杂的药代动力学而很难剂量，但它仍然是疗养院最常开出的抗癫痫药物(AED)，在美国大约150万居民中有6%的人接受了它的治疗。PHT是一种很难剂量达到最佳治疗结果的AED，因为它的消除动力学是非线性的，它在患者体内的浓度可能非常可变(不稳定)，并且它改变了在该人群中使用的许多其他药物的代谢。较新的AEDs，如拉莫三嗪(LTG)和左乙拉西坦(LEV)似乎具有更理想的药代动力学特征，使用它们可能会导致比使用PHT更好的结果。然而，没有关于疗养院使用AED的结果，正确使用AED浓度来指导管理，以及使用较旧的AED与较新的更昂贵的AED的成本效益的信息。我们小组发现，在许多疗养院患者体内，PHT浓度波动明显，即使在剂量和联合用药没有变化的情况下也是如此。这些患者中有64.3%的波动大于5ug/ml，据报道，这种变化会增加其他人群的癫痫发作活动。此外，许多患者的PHT浓度高于与不良事件相关的浓度。这项研究将首次收集接受PHT、LTG和LEV治疗的老年疗养院居民抽血时的前瞻性结果信息(癫痫发作和不良事件)。结果将有助于确定这些AEDs的适当水平以实现最佳结果，确定与PHT水平不稳定相关的因素，确定较新的AEDs是否与较少的不良事件相关，评估测量AEDs的有用性，并确定总成本(药物、住院、护理时间等)。在疗养院环境下的AED治疗。我们在两个地理区域(明尼阿波利斯和纽约)招募了四个主要的养老院地点，对超过7000名居民进行了床位普查。我们将招募200名疗养院居民进行AED治疗，以获得175名受试者的研究组(50名LEV，50名LTG，75名PHT)。他们将在大约9个月的时间里接受五次研究。该项目的长期目标是为养老院居民使用抗癫痫药物提供第一个循证建议的基础。

DESCRIPTION (provided by applicant): Although phenytoin (PHT) has been attributed to falls in the elderly and is very difficult to dose due to complicated pharmacokinetics, it continues to be the most frequently prescribed antiepileptic drug (AED) in nursing homes with 6% of the approximately 1.5 million residents in the United States receiving it. PHT is a difficult AED to dose for optimal therapeutic outcome because its elimination kinetics are nonlinear, its concentrations within a patient can be extremely variable (unstable), and it alters the metabolism of many other medications used in this population. Newer AEDs such as lamotrigine (LTG) and levetiracetam (LEV) appear to have more desirable pharmacokinetic characteristics and their use may lead to better outcomes than use of PHT. However, there is no information regarding the outcomes of AED use in nursing homes, the proper use of AED concentrations to guide management, and the cost-effectiveness of using older AEDs versus newer more expensive ones. Our group discovered that PHT concentrations fluctuate markedly within many nursing home patients even when there is no change in dose and no change in co-medications. The fluctuations in 64.3% of these patients were greater than 5 ug/ml, a change that has been reported to increase seizure activity in other populations. In addition, many patients had PHT concentrations above those that have been associated with adverse events. This study will be the first to collect prospective outcome information (seizures and adverse events) at the time of a blood draw in elderly nursing home residents treated with PHT, LTG, and LEV. Results will help define the appropriate levels of these AEDs for optimal outcomes, identify factors associated with instability of PHT levels, determine if the newer AEDs are associated with fewer adverse events, evaluate the usefulness of measuring AEDs, and determine the total costs (drug, hospitalizations, nursing time, etc.) of AED therapy in the nursing home setting. We have recruited four major nursing home sites in two geographical regions (Minneapolis and New York) with a combined bed census of over 7,000 residents. We will enroll 200 nursing home residents on AED therapy to attain a study group of 175 subjects (50 LEV, 50 LTG, 75 PHT). They will be studied five times over approximately a 9-month period. The long-term goal of this project is to provide the foundation for creating the first evidence-based recommendations for the use of AEDs for nursing home residents.