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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Clinical Neuroscience and Disease Study Section (CND)
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Wise, Bradley C
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University of Minnesota Twin Cities
Schools of Medicine
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