Seizure disorder is one of the most common neurological conditions affecting two percent of the population worldwide, and almost two million people in the United States alone. The incidence of seizures sharply rises after age 60, and among all age groups, those over the age of 60 have the highest incidence of acute symptomatic seizures and mortality from status epilepticus. While many studies have examined the impact of epilepsy in the general population, little attention has been focused on older patients with epilepsy.
Why should we treat elderly patients differently for their seizure disorder? First of all, the pharmacokinetics and pharmacodynamics of antiepileptic drugs (AEDs) may be altered by advancing age. For example, decreased plasma protein binding, decreased renal drug clearance, decreased hepatic oxidation, and longer elimination half-life may occur, all of which influence overall tolerability and susceptibility to AEDs. Additionally, older patients are also more likely to be receiving multiple medications for concurrent diseases, thereby increasing the possibility of drug interactions and affecting efficacy. For example, hepatic enzyme inducing AEDs (i.e., phenytoin, phenobarbital, and carbamazepine) can decrease the efficacy of concurrent anti-hypertensive or cholesterol-lowering agents, and interaction with narrow therapeutic index medications such as warfarin or digoxin is a significant concern for elderly patients with epilepsy and cardiovascular disease. Conversely, commonly used medications such as cimetidine and fluoxetine inhibit the metabolism of carbamazepine, phenytoin, and valproate, possibly causing toxicity from these AEDs.
Secondly, older patients have different etiologies of epilepsy and may present with different diagnostic problems and treatment responses. Differences in underlying etiology may warrant not only a different approach to diagnostic evaluation, but also different treatment considerations. For instance, ticlopidine is widely used among patients who have cerebrovascular disease, which is the most common etiology for epilepsy in the elderly, but it may cause phenytoin and carbamazepine toxicity due to CYP2C19 inhibition. In addition, prolonged seizures or status epilepticus could be the first presenting signs in the elderly as opposed to younger patients, and the mortality from status epilepticus is known to be higher in older patients.
Finally, in comparison to younger adults, older individuals may be more susceptible to cognitive and other side effects of AEDs. They may already have declining cognitive and memory function, which may make them more susceptible to the cognitive side effects of AEDs. Although many comparative drug studies have been performed in younger patients, very few clinical studies have compared the cognitive side effects of AEDs in older patients with epilepsy. Although one multicenter randomized study (mean age 77 years) showed that lamotrigine was superior to carbamazepine on the basis of patient completion, fewer side effects, and better patient outcome, more studies are needed to know which AEDs are better tolerated in elderly patients with epilepsy. In addition, previous studies found that enzyme inducing AEDs are commonly associated with osteopenia and osteoporosis. There are consequently growing concerns with regard to AED therapy induced osteoporotic changes and bone fracture in the elderly epilepsy population and associated side effects leading to falls and accidental injury.
So the pressing question remains: Should we treat elderly seizure patients differently? This current issue of Hot Topics in Neurology and Psychiatry is devoted to the treatment of seizures in elderly patients and the management of their status epilepticus. The two chapters discuss diagnostic and treatment challenges in this population, as well as alternative and emerging treatment options. I trust it will guide you in the decision making process as you treat your elderly patients with epilepsy.