The Management of Epilepsy in Older Adults: Part 1

Dr. Robert T. Wechsler, MD, PhD, FAAN is a Board-certified epileptologist and neurologist in private practice in Boise, Idaho. He serves as Medical Director of the Idaho Comprehensive Epilepsy Center, Board President of the Epilepsy Foundation of Idaho, is an active member of the Epilepsy Studies Consortium, and has been involved as a clinical investigator in a large number of epilepsy clinical trials. He is also co-Editor of the medications section of epilepsy.com. Dr. Wechsler has provided consulting services and has done promotional work for a variety of pharmaceutical companies. In this series, Dr. Wechsler shares his perspective on the treatment of epileptic seizures in older adults. The second installment of this series will appear in the June issue.  

As was reviewed in the April issue, epilepsy is one of the most common neurological conditions in the US and is characterized by seizures that emerge as a result of abnormal, hyper-synchronous electrical discharges in the brain. While it was once thought of as a disease of the very young, it has been well-established that older adults are among the fastest growing segment of the epilepsy population.1,2 Any brain injury can predispose to the subsequent development of epileptic seizures and, given progressively improved survival following brain injuries related to ischemic and hemorrhagic strokes, traumatic brain injuries, neoplasms, and other conditions, the incidence of associated epilepsy in older adults also has grown. The majority of new cases of epilepsy in older adults are secondary to some sort of focal brain injury and are thus focal epilepsies. Focal epileptic seizures can manifest with a variety of clinical symptoms—sensory or motor, with or without impairment of consciousness (formerly called simple partial seizures and complex partial seizures, respectively), and with or without progression to secondary generalized tonic-clonic seizures (if the seizure progresses to diffusely involve the brain bilaterally). This is distinct from the primary generalized epilepsies that most often emerge in childhood, are likely genetically determined, and are characterized by seizures that are thought to originate in bilaterally-distributed networks (absence seizures, myoclonic seizures, and primary generalized tonic-clonic seizures). This is also distinct from the syndromic epilepsies that typically are associated with a variety of cognitive and developmental disabilities and a variety of seizures types in various combinations (all listed above as well as atypical absence seizures, tonic seizures, and atonic seizures). While the primary generalized epilepsies and the syndromic epilepsies most often manifest in childhood, this is not always the case and, even when they do, they can persist into adulthood and the elder years. For example, yes, it is possible for an elderly person to have juvenile myoclonic epilepsy (JME) or absence epilepsy that was never outgrown—and perhaps never diagnosed. In fact, only a minority of JME cases are ever outgrown, and it is a relatively common type of primary generalized epilepsy. Treatment choices can vary, depending on epilepsy type, so it is important to know the diagnosis before initiating or changing therapy. In the modern era of epilepsy care, we have dozens of anti-seizure medications from which to choose and can achieve seizure-freedom in at least two-thirds of patients, with few or no side effects. The goals of epilepsy management should be (1) no seizures and (2) no side effects.

ALTC: Can you speak to the importance of accurately diagnosing the type of epilepsy in older adults before considering treatment?
It has been estimated that at least two-thirds of people living with epilepsy can achieve complete seizure freedom with medication, often with few side effects, and this success may be even easier to achieve in older adults. Knowing the epilepsy classification is critical to choosing appropriate treatment because it can have substantial impact on therapeutic choices. As a general rule, the anti-seizure medications are broadly divided into those with a broad spectrum of action and those with a narrow spectrum of action, conceptually similar to antibiotics. Broad spectrum anti-seizure medications cover a variety of seizure types and are safe to use in cases where the epilepsy type is not known. Narrow spectrum anti-seizure medications most often work in focal epilepsies but can exacerbate some generalized seizure types—most often absence seizures or myoclonic seizures. This classification is not yet defined for some of the newest epilepsy medicines. Due to the prevalence of focal epilepsy in adults, this is the population in which novel treatments are most often studied and for which those treatments are first approved. Studies assessing efficacy in generalized epilepsies may follow years after approval or may never be done. Regardless of study type, older adults typically make up a relatively small proportion of study populations. Consequently, publications of the effects of anti-seizure medications in older adults often are delayed or are reported as sub-analyses.^3,4,5 The clinician is often left to extrapolate the likely effects of these anti-seizure medicines on older adults based on the reported efficacy, safety, and tolerability observed in the total population studied.

What are some of the nonpharmacologic approaches to treating epilepsy in older adults and improving their quality of life?
An important first step toward seizure control in all patients, including older adults, is to focus on avoiding triggers. Seizures can be triggered by missed medication doses, sleep deprivation, excessive use of alcohol, excessive stimulants, and a variety of physical and emotional stressors, including concurrent illnesses. Even an upper respiratory infection or an uncomplicated urinary tract infection in an older adult can lower seizure threshold in cases of previously well-controlled epilepsy. While no one can avoid all triggers all the time, it is important to avoid multiple triggers. For example, it is important to get plenty of rest while otherwise ill and to make sure that anti-seizure medications are taken consistently.
The best thing clinicians can do to improve quality of life in their epilepsy patients is to pay attention to each patient’s experience. People with epilepsy are at substantially increased risk for depression. They should be screened for it, and it should be treated. Side effects also can have a substantial negative impact on quality of life, even if seizures are controlled. Most of the common side effects associated with anti-seizure medications include things like dizziness, diplopia, fatigue, and somnolence—things one would expect to see with CNS depressants. These can be debilitating in some patients. It is important to keep in mind, however, that anti-seizure medications are not interchangeable—an individual patient may have intolerable side effects to one drug but tolerate another without difficulty.  The next patient might have the opposite experience. It is important to keep trying therapeutic options until side effects are minimized. Remember that the goal is no seizures and no side effects. Physicians like to discuss the benefits of once daily dosing in terms of improved adherence but once daily dosing of anti-seizure medicines in the evening also improves quality of life because any dose-dependent side effects that are encountered can be experienced while asleep in bed at night.
Many people ask about dietary treatments for drug-resistant epilepsy, but the value of such diets in older adults is uncertain. The diets tend to be high in fat with little protein and avoidance of carbohydrates. The impact of such diets on the overall health of older adults is not clear. These diets are typically used in children with catastrophic epilepsy, usually for a short duration. The media has recently given an unprecedented amount of attention to cannabinoids and medical marijuana in the treatment of epilepsy but, as of 2015, the science is lacking, the evidence is largely anecdotal, and any benefit these agents may provide will likely not live up to the unrealistic hope that has been generated. Patients with epilepsy living in states where such agents are available and who insist on trying them should do so very cautiously and under the guidance of an experienced physician. There have been anecdotal reports of marijuana exacerbating seizures, but these have not received as much media attention.

References:
1.    Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia. 1993;(34):453-468.

2.    Rowan AJ, Ramsay RE, Collins JF, et al. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005;64(11):1868-1873.

3.    Wechsler RT, Leroy R, Van Cott A, et al. Lamotrigine extended-release as adjunctive therapy with optional conversion to monotherapy in older adults with epilepsy. Epilepsy Res. 2014;108(6):1128-1136.

4.    Runge U, Mayer T, Noack-Rink M, et al. Lacosamide added to an existing monotherapy in epilepsy patients with partial-onset seizures: a subgroup analysis of older adults population in the VITOBA study. Paper presented at: American Epilepsy Society 68th Annual Meeting; 2014; Seattle, WA. Abstract 3.297.

5.    Leppik IE, Wechsler RT, Williams B, et al. Efficacy and safety of perampanel in the subgroup of elderly patients included in the phase III epilepsy clinical trials. Epilepsy Res. 2015;110:216-220.