Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics.

OBJECTIVE: To evaluate antiepileptic (AE) use by nursing home residents. DATA SOURCES: Medical records for 996 residents from six Minnesota nursing homes (5% of the nursing home residents in the Minneapolis-St Paul area) compared with medication records of 45,405 nursing home residents nationwide serviced by Pharmacy Corporation of America, Boulder, Colo. STUDY SELECTION: Reports comparing pharmacokinetics in younger adults and elderly volunteers or patients with epilepsy who were given AEs. DATA SYNTHESIS: Among Minnesota nursing home residents, 7.7% were taking AEs. Usage in a national survey was 10.1%. A review of published studies involving small numbers of elderly subjects or patients given phenytoin sodium, valproic acid, or carbamazepine demonstrates decreased protein binding and intrinsic clearance and increased half-life with advancing age. Concomitant drugs, especially those with central nervous system effects, can lower the concentration at which AEs cause dose-related side effects, thereby narrowing therapeutic ranges.
CONCLUSION: Approximately 10% of nursing home residents receive AEs, usually with other maintenance medications. In 82% of residents receiving an AE, the indication was treatment of a seizure disorder. Other indications included aggressive behavior, essential tremors, and neurologic pain. Age-related alterations in AE pharmacokinetics result in protein-binding changes and decreases in drug elimination. Measurement of unbound drug concentrations may be helpful when altered binding is suspected or clinical response does not correlate with total AE concentration. Concomitant drugs pose the risk for significant drug interactions and adverse reactions. An understanding of the underlying pharmacokinetic processes, including the need of most elderly patients for lower doses and longer dosing intervals, permits more effective management of therapy and reduces the risk for adverse reactions.