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Pharmacokinetic Factors to Consider in the Selection of Antiseizure Drugs for Older Patients with Epilepsy

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Abstract

The incidence of epilepsy is highest in the older adult age group. Seizures in older adults can be more difficult to diagnose because their presentation is often subtle and can easily be mistaken for other conditions. Fortunately, new-onset epilepsy in the older adult is often pharmaco-responsive, with as many as 80–85% of patients achieving remission, often with monotherapy at modest doses. Many physiological and pathological changes occur with aging that can alter the pharmacokinetics of antiseizure drugs (ASDs). For the majority of the old- and new-generation ASDs, a decrease in dose may be needed to maintain concentrations equivalent to those found in young adults. The risk of drug interactions with ASDs is substantial, as polypharmacy is common. The first-generation ASDs (carbamazepine, phenytoin, phenobarbital, and valproic acid) have the potential to interact with many drugs, but many newer ASDs either do not have significant interactions or are selective inhibitors and inducers of specific hepatic enzymes. The differences in adverse effects between younger and older adults are not just due to dosing and pharmacokinetics. Older adults are more susceptible to the gait, balance, and cognitive effects of ASDs. Overall, the improved tolerability and decreased drug interaction potential of the newer-generation ASDs, such as lamotrigine and levetiracetam, have demonstrated their superiority in the treatment of seizures in older adults and, as such, are clearly favored for new-onset epilepsy in older adults.

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Authors and Affiliations

  1. Department of Pharmacy and Regional Epilepsy Center, University of Washington, Seattle, WA, 98195, USA

    Gail D. Anderson

  2. Department of Neurology and Regional Epilepsy Center, University of Washington, Seattle, WA, 98195, USA

    Shahin Hakimian

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Correspondence to Gail D. Anderson.

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Conflicts of Interest

Gail Anderson has no conflicts of interest directly relevant to the content of this article. Shahin Hakimian has participated in clinical trials involving several antiepileptic drugs, a few of which are discussed in this article, as a local co-primary investigator. He has not received any salary support or contribution for his participation. Shahin Hakimian has also consulted for a pharmaceutical drug benefits company, OptumRx, which has no relation to or influence on the current manuscript.

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Anderson, G.D., Hakimian, S. Pharmacokinetic Factors to Consider in the Selection of Antiseizure Drugs for Older Patients with Epilepsy. Drugs Aging 35, 687–698 (2018). https://doi.org/10.1007/s40266-018-0562-2

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