The incidence of new-onset seizures in the elderly population is increasing. With comparatively few studies of new-onset seizures in the elderly, and no specific guideline for treating elderly patients with seizures, physicians are challenged to determine the best treatment approaches for these patients. Today, new-onset epilepsy in the elderly is about three times more common than epilepsy in younger people, according to Ilo Leppik, MD, director of research at MINCEP Epilepsy Care and professor of pharmacology and neurology at the University of Minnesota in Minneapolis. “Epilepsy is more common after age 50 than in almost any other age group,” he said. New-onset epilepsy may be four or five times more common among octogenarians or nonagenarians than among children. Because of the aging population in the United States, “there’s going to be an epidemic of epilepsy in the elderly,” said Dr. Leppik.

Dr. Ilo Leppik

Factors contributing to the increased incidence in the elderly include stroke, head trauma, bleeding in the brain, neurodegenerative diseases, and brain tumors, said Nikesh Ardeshna, MD, medical director of epilepsy services at McLaren Macomb Hospital in Mount Clemens, Mich. He cited research by Birnbaum et al. that indicates that among elderly residents of nursing homes, the neurologic conditions with the strongest associations with epilepsy or seizures are brain tumor, head injury, and stroke. But for many patients, the first seizure arises spontaneously, and clinicians may fail to identify a specific cause. Dr. Leppik’s research indicates that 6%-7% of all patients in nursing homes have epilepsy. Epilepsy may be as much as 10 times more common in this setting than in the general elderly population. Diagnosis is challenging Epilepsy is not always easy to diagnose in the elderly. Seizure presentation tends to be more subtle in this population. In the elderly, focal seizures with impaired awareness are more common than tonic-clonic seizures are, said Joseph I. Sirven, MD, professor of neurology at Mayo Clinic in Phoenix. Complex partial seizures may be the most common presentation, said Dr. Ardeshna. Nevertheless, many elderly patients with epilepsy present with nonspecific symptoms such as confusion, abnormal movements, memory loss, and wandering. Such symptoms can be attributed mistakenly to other illnesses that are common among the elderly, such as memory loss, dementia, or delirium. In addition, diagnosis is harder when a patient has no prior history or family history of seizures. Diagnostic delays are common, said Dr. Ardeshna.

Questions about treatment are unresolved After a patient has had a seizure or received a diagnosis of epilepsy, the next question is when and how to treat him or her. One factor that complicates this question is the fact that internists, family practitioners, and nursing home staff often make these decisions, rather than neurologists. Non-neurologists may be much more likely to treat a first seizure than a neurologist is, but whether this is the correct approach is uncertain. The question of when to treat remains unresolved, and much more research is necessary, said Dr. Leppik. A major goal of treatment is to maintain quality of life, which is especially important in the elderly, said Dr. Ardeshna. Seizures can lead to the revocation of driving privileges, which affects the patient’s activities of daily living (e.g., grocery shopping and social events) and living arrangements. When choosing pharmacotherapy, a clinician should consider how each antiepileptic drug (AED) affects the patient’s quality of life, said Dr. Ardeshna. Unfortunately, the literature provides insufficient evidence to guide the treatment of elderly patients with new-onset epilepsy, he added. Potential drug interactions are a concern Nevertheless, certain basic principles can help clinicians make treatment decisions. “The most important consideration is to pick a drug that has the lowest chance of having possible drug interactions,” said Dr. Leppik. Comorbidities, including Alzheimer’s disease, stroke, and cardiovascular disease, are more common in the elderly than among other age groups. Consequently, elderly patients take many medications. “An elderly person in a nursing home may be on as many as 14 medications, including the epilepsy medication,” said Dr. Leppik. credit: dszc/Getty Images

These medications may interact with AEDs, and vice versa. Such interactions can change plasma concentrations of AEDs or medications for comorbidities. Iron supplementation, for example, is associated with reduced absorption of carbamazepine. Coadministration of carbamazepine and simvastatin results in lower-than-expected serum concentrations of simvastatin. In addition, one medicine may cause side effects that counteract the desired effect of another drug, said Dr. Leppik. Drugs that are metabolized in the liver are likely to cause drug–drug interactions, said Elinor Ben-Menachem, MD, guest professor of clinical neuroscience at the University of Gothenburg in Sweden. One such drug is carbamazepine. Fortunately, it is possible to choose an AED that will not interfere with the treatment of comorbidities. Lacosamide, levetiracetam, topiramate, gabapentin, and pregabalin have minimal interactions with other medications, said Dr. Sirven. Lamotrigine and brivaracetam also may be appropriate choices. Appropriate treatment of comorbidities also may reduce the risk of seizures, Dr. Sirven added. For example, most seizures among the elderly are secondary to stroke, and therapies that prevent stroke may prevent seizures, said Dr. Sirven. Side effects are common in the elderly Another goal is to avoid side effects. The elderly are more at risk for adverse events than are younger patients, and common side effects include drowsiness, fatigue, gait instability, and dizziness, said Dr. Ardeshna. Unpleasant side effects can reduce compliance, thus increasing the risk of breakthrough seizures. But choosing medications with few or no side effects can be difficult, Dr. Ardeshna added. An elderly patient may have impaired bone health resulting from osteoporosis or osteopenia. Enzyme-inducing AEDs, most of which are older drugs, cause a faster deterioration of bone health, said Dr. Ardeshna. Choosing a newer, non–enzyme-inducing AED may reduce the risk of further impairing bone health, he said. In addition to bone health, balance often is impaired among the elderly, which makes them prone to falls. Some AEDs cause side effects such as dizziness or gait instability that increase the risk of falls. Apart from causing injury, falls can lead to head trauma: a major cause of seizures. Avoiding AEDs that can make falls more likely is thus an important consideration in choosing treatment for elderly patients. Carbamazepine, oxcarbazepine, and eslicarbazepine can cause hyponatremia, which can be a problem for elderly patients, said Dr. Ben-Menachem.

Metabolism and compliance To treat appropriately and effectively, a clinician must understand the pharmacokinetics of any medication that he or she prescribes, said Dr. Leppik. Understanding how to interpret blood levels is integral to treatment monitoring, he added. A drug’s pharmacokinetics are likely to differ in elderly patients, compared with patients of other age groups. “Metabolism is slower [among the elderly], so medications are likely to produce more adverse effects,” said Dr. Sirven. “Thus, lower doses of medications are needed.” Elderly patients may have lower kidney function or gastrointestinal problems that affect drug concentrations and bioavailability, said Dr. Ben-Menachem. “Usually, [for] elderly people, it is advisable to begin treatment with a low dose and titrate up slowly, because the elderly may tolerate less, especially if there is renal impairment.” In a 2018 study, Polepally et al. found that lamotrigine clearance was 27.2% lower in elderly patients, compared with younger patients of similar body weight. They suggested that lower doses of the drug may therefore be appropriate for the former population. Similarly, a study by Sourbron et al. found that age and the use of enzyme-inducing drugs significantly influence the pharmacokinetic profile of levetiracetam. They concluded that the dose of this drug should be 30%- 50% lower in patients older than 65 years. Clinicians can be reassured that elderly onset epilepsy often is easy to control, said Dr. Ben-Menachem. Elderly patients are less likely to have refractory epilepsy than other groups are. Data from large clinical trials also suggest that AEDs have greater efficacy among elderly patients. Thus, seizures often can be controlled, provided that patients understand how to take their medicines and take them as prescribed, Dr. Ben-Menachem added. Surgery may be an option Resective surgery is an accepted option for many children and adults, but neurologists may hesitate to recommend, or even consider, this treatment for the elderly. The main reason for this aversion is that epilepsy surgery entails the risk of cognitive deficits, which are particularly undesirable in elderly patients who may already be cognitively compromised, said Dr. Ben-Menachem. This hesitation may be unwarranted, however. Provided that they have limited comorbidities, elderly patients with epilepsy can be considered surgical candidates, said Dr. Sirven. In 2017, Punia et al. reported a case series that included seven septuagenarians who underwent anterior temporal lobectomy. Median follow-up duration was approximately 2 years. Six of the patients had Engel Class I or Class II outcomes, and four were completely free of disabling seizures. Four of the patients underwent neuropsychological testing before and after surgery, and three had a decline in memory function after the resection. “Our experience suggests that resective epilepsy surgery can be a safe and effective therapy in well-selected, septuagenarian patients with drug-resistant epilepsy,” said the authors.

Conclusion Most epilepsy research focuses on children and adults; comparatively few studies have examined the elderly. Furthermore, no official guideline for treating elderly patients with seizures is available. Nevertheless, some data are emerging as more clinicians recognize the growing incidence of epilepsy in this population. By bearing in mind considerations related to seizure presentation, metabolism, comorbidities, and drug–drug interactions, neurologists and other health care professionals can choose appropriate, safe, and effective treatment regimens for their elderly patients with epilepsy. References 1. Leppik IE et al. Analysis of falls in patients with epilepsy enrolled in the perampanel phase III randomized double-blind studies. Epilepsia. 2017;58(1):51-9. 2. Birnbaum AK et al. Prevalence of epilepsy/seizures as a comorbidity of neurologic disorders in nursing homes. Neurology. 2017;88(8):750-7. 3. Ahn JE et al. Iron supplements in nursing home patients associated with reduced carbamazepine absorption. Epilepsy Res. 2018;147:115-8. 4. Polepally AR et al. Lamotrigine pharmacokinetics following oral and stable-labeled intravenous administration in young and elderly adult epilepsy patients: Effect of age. Epilepsia. 2018;59(9):1718-26. 5. Sourbron J et al. Review on the relevance of therapeutic drug monitoring of levetiracetam. Seizure. 2018;62:131-5. 6. Punia V et al. Breaking the age barrier: Epilepsy surgery in septuagenarians. Epilepsy Behav. 2017;70(Pt A):94-6.