Incidence of New-Onset Epilepsy in the Elderly May Increase

WASHINGTON, DC —Neurologists may face “an epidemic” of new-onset epilepsy in the elderly as the nation’s population ages, said Ilo Leppik, MD, at the 67th Annual Meeting of the American Epilepsy Society. The predicted increase in incidence highlights the comparative scarcity of data on epilepsy in this population and the need for more research, he added.

Epilepsy was regarded as a disease of children for many years, but as researchers gathered more data on an aging population, they found that the incidence of new-onset epilepsy increased among people older than 50. They reported an incidence of 169/100,000 per year in this population—almost twice the incidence among children.

Stroke is the most common cause of epilepsy in people older than 65. The prevalence of new-onset epilepsy is about three times higher among people 65 or older than among people younger than 65. And a study of approximately three million patients in the Medicare database suggested that the incidence of new-onset epilepsy could be as much as 10 times higher among people in nursing homes than among elderly individuals living in the community.

Comorbidities May Affect Choice of AED
“Management of epilepsy in the geriatric population is complicated,” said Dr. Leppik, Professor of Pharmacy and Neurology at the University of Minnesota in Minneapolis. “It makes taking care of intractable adult epilepsy [look like] a piece of cake.” Visual impairments, memory problems, and inability to take oral medications may pose challenges for compliance. In addition, comorbidities among the elderly can add to their medication burden and complicate the task of choosing an appropriate antiepileptic drug (AED).

Few studies have examined AEDs’ interactions with other medications, but the literature does offer some guidance. Carbamazepine may reduce serum concentrations of simvastatin by nearly 70%. “I don’t like to use carbamazepine in the elderly because of its sodium-depleting quality,” which could be especially problematic for patients receiving antihypertensives, said Dr. Leppik. Some evidence suggests that the newer AEDs are superior to carbamazepine. In addition, one study found that enzyme-inducing AEDs reduce plasma levels of anticoagulants such as warfarin by as much as 50%.

Another trial analyzed 593 elderly patients with newly diagnosed seizures who were randomized to 1,500 mg/day of gabapentin, 150 mg/day of lamotrigine, or 600 mg/day of carbamazepine. The rate of early termination was higher among patients receiving carbamazepine than among patients receiving the other medications, but all three AEDs provided similar seizure control. The study would have been more informative if it had included levetiracetam, said Dr. Leppik, but the drug was not available while the trial was being conducted.

The most important principle in choosing an AED for an elderly patient is to select a drug that does not interact with other medications, said Dr. Leppik. Gabapentin and levetiracetam may be appropriate options because the body does not metabolize them. Neurologists should have an IV preparation of the AED available for patients who become incapable of taking medication orally. Dosage forms such as suspensions or sprinkles also may aid compliance. And, in general, neurologists treating elderly individuals should favor drugs with long half-lives, Dr. Leppik added.

Treatment After First Seizure May Be Appropriate
A patient’s age may influence a neurologist’s decision about when to treat a person with a seizure. Elderly people who have had one seizure may be at greater risk of a second seizure than younger individuals are; thus neurologists may consider treating an elderly person after a first seizure to prevent a second seizure.

A prospective observational study conducted in Australia between 2000 and 2011 examined the likelihood of a second seizure among adults at one year. The rate of second seizure was 53% among patients 65 or older and 48% among individuals younger than 65, but the investigators did not state whether any patients were treated after their first seizure. The researchers concluded that remote symptomatic etiology, but not age, was an independent predictor of a second seizure. Nevertheless, “the elderly probably ought to be looked at carefully for treating after the first seizure, more so than a younger person or a child,” because the risk of falls, fractures, and cardiovascular stress may put the elderly at greater risk of serous sequelae, said Dr. Leppik.

Drug Monitoring May Be Indicated
In addition, neurologists should bear age-related changes in mind when treating an elderly patient with epilepsy. For example, age generally changes a patient’s rate of drug absorption and dosing range. Elderly patients may need lower concentrations of a drug to achieve clinical efficacy. These individuals “seem to be more easily treated” and “do not seem to be as therapeutically resistant,” said Dr. Leppik. Drug binding also may vary with age and with the use of drugs that may compete for binding. But drug toxicity also may be achieved at lower blood levels in elderly patients, and side effects may be of greater concern in this population as well.

In light of these age-related changes, therapeutic drug monitoring may be necessary for elderly patients. Neurologists should perform therapeutic drug monitoring when a patient has obtained at least four half-lives, which tend to be longer in the elderly, said Dr. Leppik. In addition, drug monitoring is indicated when a patient has side effects related to the AED, breakthrough seizures, or a change in health status. “We obviously have to do much more research in this … growing population,” Dr. Leppik concluded.

—Erik Greb