May/June 2024

May/June 2024 Issue

Epilepsy in Older Adults
By Mark D. Coggins, PharmD, BCGP, FASCP
Today’s Geriatric Medicine
Vol. 17 No. 3 P. 10

The incidence and prevalence of epilepsy increase with age.

Epilepsy is the third most common neurological disorder affecting adults older than 65, after stroke and dementia.1 Epilepsy can reduce a person’s independence and is associated with increased physical concerns (eg, falls and fractures) and psychological issues (eg, anxiety and depression), and an increased risk of premature death.

While people of all ages can be affected, the incidence and prevalence of epilepsy increase with age and are highest in older adults. Making an accurate diagnosis of new-onset epilepsy in older adults is challenging as the clinical manifestations of the disorder in this population are subdued and misidentified as other conditions, including dementia and stroke. Treatment decisions are also more complex in older adults due to age-related physiological changes, increased comorbidities, and polypharmacy. As the population ages rapidly, there will be a significant increase in the number of older adults with epilepsy and a tremendous need for multidisciplinary coordination to help patients effectively manage the condition.

Epilepsy vs Acute-Onset Seizures
Epilepsy is a neurological condition characterized by recurrent (two or more) unprovoked seizures—those occurring in the absence of a provocative cause or more than seven days after an acute injury or insult, such as stroke or brain hemorrhage.2 Epileptic seizures arise spontaneously and are expected to recur in the absence of treatment. In contrast, provoked seizures (also called acute-onset seizures) occur due to an identifiable proximate cause or trigger (eg, hypoglycemia, alcohol withdrawal, and many others). Provoked seizures are not expected to recur in the absence of that cause or trigger.

Epidemiology
Age is an independent risk factor for seizures and epilepsy.3 Nearly one million adults older than 55 have active epilepsy.4 The incidence of epilepsy and seizures increases sharply in adults older than 60 years,5 with the prevalence being highest in patients 75 and over.6 Further, the incidence rate of new-onset epilepsy in older adults is estimated to be two to six times higher than that in younger adults.7 Similarly, the prevalence of epilepsy in older adults is estimated to be three to four times higher than in younger adults.8 Nearly one-half of new-onset seizures occur in persons 65 and older.7 Recurrence rates of seizures are also higher in the older population, with 79% suffering a recurrence in the first year after a first seizure and 83% in the three years following a first seizure.9 Stroke is the most common cause of seizures in adults 60 and older.10

Etiology
The etiology of epilepsy varies across age groups. Whereas epilepsy in children is generally due to genetic causes, malformation of cerebral development, and hypoxic-ischemic encephalopathy, in young adults it’s more likely to be caused by head trauma and tumors.11 In older adults, it’s mainly the consequence of accumulated injuries to the brain and other secondary factors such as stroke and other cerebrovascular diseases, neurodegenerative disorders, intracerebral tumors, and traumatic brain injuries.11,12 About 50% of older adults will have idiopathic epilepsy.13

Stroke and Cerebrovascular Disease
Stroke and cerebrovascular disease account for 30% to 50% of all identified causes of new-onset epilepsy in older adults.12 The risk for developing seizures after a stroke ranges from 9% to 19%.14 Furthermore, persons with cerebrovascular disease have a risk of epilepsy more than 20 times that of the general population.15 A retrospective cohort study conducted on veterans aged 66 and older found that cerebrovascular disease risk factors, such as hypertension, hypercholesterolemia, and coronary and peripheral arterial disease, are associated with epilepsy, even in the absence of stroke.16 Having epilepsy also increases stroke risk. A CDC study found that about 23% of adults older than 65 with a history of epilepsy had previously experienced a stroke, compared with about 5% of older adults without epilepsy.17 Persons with late-life-onset epilepsy also have increased myocardial infarction, peripheral artery disease, hypertension, high cholesterol, and other cerebrovascular disease risk factors.18 Consequently, older patients with new-onset epilepsy should be assessed for cerebrovascular disease risk factors and provided interventions to help prevent the occurrence of cerebrovascular disease and stroke.12

Neurodegenerative Conditions
Neurodegenerative conditions like Alzheimer’s disease account for 10% to 20% of all identified cases of epilepsy.19 Persons with any dementia are at a fivefold to tenfold increased risk of epilepsy compared with similarly aged persons without dementia.20 Among older patients with dementia, 9% to 17% will develop epilepsy.21 And patients with Alzheimer’s disease are three to 87 times more likely to develop epilepsy than are the same-aged general population.22

Head Trauma
Approximately 20% of late-onset epilepsy is due to head trauma, which may occur as a result of a fall or other injury.23 Falls can also occur as a consequence of seizures. These concerns highlight the need for increased fall precautions in all older adults, with or without a history of seizures.

Brain Tumors
Brain tumors account for nearly 10% to 30% of all causes of geriatric epilepsy, second only to cerebrovascular disease and stroke.12

Focal Onset Seizures With Impairment of Awareness
Focal onset seizures with impairment of awareness (also called focal impaired awareness seizures) are the most common type of seizure in older adults who present with new-onset epilepsy.24 These begin in one side of the brain and are associated with impaired consciousness. Any decrease in awareness of self or environment at any time during the seizure makes it a focal impaired awareness seizure. Persons having the seizure may seem awake and stare into space but cannot respond to their environment. Repetitive movements such as hand rubbing, mouth movements, repeating words, or walking in circles may be observed. However, these individuals will be unable to remember or know that the seizure occurred.

Challenges in Diagnosis
Making a diagnosis of new-onset epilepsy in older adults can be difficult, and the condition is easily misdiagnosed as the diagnosing physician may not have witnessed the seizure first-hand. Factors complicating the diagnosis include an atypical clinical presentation in older patients compared with young adults, vague seizure symptoms, the presence of comorbidities, and concomitant cognitive impairment.13

Atypical Clinical Manifestations
In contrast to young adults, older adults who experience focal seizures are less likely to experience auras (feeling or sensation that a seizure is about to occur) and instead report nonspecific symptoms, such as dizziness. Automatisms (repetitive motor activities associated with impaired awareness) are less common, and postictal confusion may be prolonged (lasting hours to days). Focal onset seizures in older adults are also less likely to progress to secondary generalized tonic-clonic seizures (convulsive seizures that involve the whole body) than in younger adults.

Vague Symptoms
Symptoms used to describe seizures in older adults are often vague and hard to recognize as those of seizures. Nonspecific symptoms such as confusion, memory problems, altered mental status, sleepiness, falls, dizziness, clumsiness, and sensory changes may be reported and attributed to getting old rather than to seizures.

Symptoms that indicate an older adult may be having a seizure include the following25:

• repetitive lip smacking, hand movements, or sudden, brief jerking movements;
• episodic (occurring more than once) confusion, memory loss, or lost wordfinding ability;
• being “off” behaviorally—they may seem withdrawn, disinterested, or depressed;
• frequent, unexplained falls or “blanking out spells”; and
• convulsions.

Comorbid Conditions
Comorbid conditions commonly seen in older adults, including dementia, can lead to the misdiagnosis of seizures. The difficulty in making a correct diagnosis was demonstrated by a large VA study in which, on initial evaluation by a primary care physician or internist, epilepsy was not considered in 26% of patients who were ultimately diagnosed with new-onset epilepsy.6 Alternative diagnoses (patients could have been given more than one initial diagnosis) were altered mental status (41.8%), confusion (37.5%), blackout spells (29.3%), memory disturbance (17.2%), syncope (16.8%), dizziness (10.3%), and dementia (6.9%).6 In a case study, transient ischemic attack, depression, and metabolic or psychiatric disorders were among the initial misdiagnoses.26

Status Epilepticus
Status epilepticus is defined as a seizure with five or more minutes of continuous clinical and electrographic seizure activity or recurrent seizure activity without recovery between seizures. The incidence of status epilepticus is higher among older patients than other age groups.27 The mortality rate associated with status epilepticus varies with age and is approximately 50% among individuals older than 80 years of age.28

Seizure Triggers
Seizure triggers make it more likely for a seizure to occur in people with epilepsy. Common triggers include tiredness and lack of sleep, stress, alcohol, fever, acute medical illness, hormonal changes, substance abuse, certain medications, bright and flashing lights, and medication noncompliance.29

Specialists Make the Diagnosis
Due to the challenges in making an epilepsy diagnosis, a specialist—most commonly a neurologist or epileptologist—will need to diagnose epilepsy using a combination of observations obtained from friends, family, and caregivers; medical history; and medical tests, including blood tests, electroencephalogram, CT scan, and MRI.

Pharmacological Treatments
Medications used to treat seizures, called antiepileptic drugs (AEDs), are categorized based on the “generation” in which they were developed and introduced.

First-generation AEDs include carbamazepine (Tegretol), ethosuximide (Zarontin), phenobarbital, phenytoin (Dilantin), primidone (Mysoline), and valproate (Depakote).

Second-generation AEDs include felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), tiagabine (Gabitril), topiramate (Topamax), vigabatrin (Sabril), and zonisamide (Zonegran).

Third-generation AEDs include eslicarbazepine acetate (Aptiom), lacosamide (Vimpat), perampanel (Fycompa), brivaracetam (Briviact), rufinamide (Banzel), and stiripentol (Diacomit).

Side Effects and Drug Interactions
The decision to use AEDs should be weighed carefully due to possible drug interactions and the potential for unwanted side effects. The second- and third-generation AEDs generally provide improved tolerability and safety compared with first-generation AEDs. An estimated 60% of persons receiving AEDs will experience at least one side effect.29 AED-related side effects can range from mild to severe; common side effects include tiredness, dizziness, nausea, rash, blurred vision, nervousness, agitation, bleeding gums, chest pain, chills, confusion, depression, fever, headaches, and weight gain. AEDs can also significantly increase fall risk.

Suicide Risk
In 2008, the FDA issued a warning that all AEDs increase the risk of suicide. Despite the low risk, it’s serious. Because the benefits of AEDs likely exceed the risks, patients undergoing treatment with these medications should be made aware of the risks and advised to contact their doctors if they experience suicidal thoughts.

Additional Considerations in Older Adults
The treatment of epilepsy in older adults is more complex than in younger patients due to age-related physiological changes (eg, reduced renal function), polypharmacy, and a higher incidence of comorbid conditions. Selection of an AED in older adults takes into consideration the type of seizure experienced, the potential for adverse drug events and drug-drug interactions, comorbid medical conditions, mode of administration required (eg, oral vs crushed vs gastrostomy tube), and cost.

Older adults are more sensitive to the adverse effects of medication, even at lower doses. They also are at greater risk of drug-drug interactions due to polypharmacy. When initiating AEDS in older adults, it’s imperative to use the lowest possible dose and increase the dose slowly to minimize the risk of adverse drug effects.

Prescribers must consider declining renal and hepatic function in older adults due to age-related pharmacokinetic and pharmacodynamic changes. Creatinine clearance should be used to dose AEDs renally eliminated. Similarly, medications metabolized by the liver may require reduced dosages.

The potential for drug-drug interactions is more likely in those using first-generation AEDs. Carbamazepine, phenobarbital, phenytoin, and primidone can induce hepatic enzymes, decreasing the effects of other AEDs and other medications metabolized by the liver. Valproic acid can inhibit hepatic enzymes, thereby increasing the effects of other AEDs and medications metabolized by the liver. Conversely, other drugs, which may be hepatic enzyme inhibitors or inducers, can also cause an increase or decrease in blood levels of these AEDs.

Low albumin levels are common in older adults, leading to increased free fraction of phenytoin (the active fraction) and other highly protein-bound drugs. This can increase the risk of phenytoin toxicity despite drug levels that may appear to be within the normal therapeutic range.

Physicians who treat epilepsy in older adults must be intimately familiar with the AEDs they prescribe to help minimize medication- related problems. Pharmacists are a valuable resource in helping to monitor epilepsy patients’ drug therapies, including the potential for drug-drug interactions.

When Is Pharmacological Treatment Recommended?
Treatment with an AED may not be indicated in some persons with a single unprovoked seizure. Recommendations about whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the adverse effects of AED therapy, consider educated patient preferences, and advise patients that immediate treatment does not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent two years.30

However, patients who experience recurrent seizures are at a substantially increased risk for future seizures.9 For this reason, it’s most often recommended to begin treatment with an AED if a person has experienced two or more well-documented (eg, high certainty of diagnosis, witnessed) unprovoked seizures.31 Evidence-based guidelines from the American Academy of Neurology and the American Epilepsy Society recommend that for patients with new-onset focal epilepsy or unclassified generalized tonic-clonic seizures, lamotrigine use should be considered (Level B) and gabapentin use may be considered (Level C) to decrease seizure frequency in patients aged 60 years or older.

These recommendations are based on the analysis of evidence from two studies demonstrating that lamotrigine was probably more effective and better tolerated than immediate-release carbamazepine but not controlled-release carbamazepine, and one study indicating that gabapentin is possibly as effective and better tolerated than immediate-release carbamazepine in patients 60 years of age or older with new-onset focal epilepsy or unclassified tonic-clonic seizures.

A Multidisciplinary Approach Is Needed
A multidisciplinary approach is required to provide the best care to older patients with epilepsy and goes beyond focusing solely on seizure control. All team members should emphasize seizure precautions, including avoiding heights, fall safety, driving, unsupervised bathing or swimming, and use of heavy machinery. The Epilepsy Foundation’s website includes a section titled “Staying Safe” (www.epilepsy.com/preparedness-safety/staying-safe) that highlights risks and tips to help keep people with seizures safe. Older patients with seizures frequently have comorbid conditions that may require treatment and take medications that may require coordination between attending physicians, neurologists, and psychiatrists. Pharmacists should monitor for drug-drug interactions, possible dosage adjustments due to older adults’ decline in renal and hepatic function, medications that decrease the seizure threshold, and medication adherence, and report any concerns to prescribers. Nurses, therapists, social workers, and other team members who may interact with older adults with seizures should look for and report potential AED adverse effects, including gait instability, excessive sedation, worsening cognitive performance, and others that indicate the need to lower medication doses.

— Mark D. Coggins, PharmD, BCGP, FASCP, is a long term care expert and corporate pharmacy consultant for Touchstone-Communities, a leading provider of senior care that include skilled nursing care, memory care, and rehabilitation for older adults throughout Texas. He’s a past director of the American Society of Consultant Pharmacists and was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the Excellence in Geriatric Pharmacy Practice Award.