Older adults in the United States who were diagnosed with new-onset epilepsy were frequently prescribed older, outdated antiepileptic drugs (AEDs), and about half experienced delays in treatment beyond 30 days, according to an analysis of a large, racially diverse database of US Medicare beneficiaries published in the February 7 online edition of Epilepsia.
“Our findings highlight two points of concern: Many older people do not receive medication after a diagnosis of epilepsy, and many older people receive outmoded drugs which may produce more side effects and may have dangerous interactions with non-epilepsy drugs,” Maria Pisu, PhD, associate professor of preventive medicine at the University of Alabama at Birmingham, said in an interview with Neurology Today.
“Physicians should be alert to the possibility of seizures in older persons. These seizures may present as subtle staring spells and be misdiagnosed as TIAs [transient ischemic attacks] or inattention,” Dr. Pisu said. “Physicians should also be aware that seizures in this age group are likely to recur, and should be properly treated.”
Dr. Pisu pointed out, however, that most adults were prescribed monotherapy in accordance with consensus guidelines [see “Quality Indicators of Epilepsy Treatment”], and treatment patterns were broadly similar across racial and ethnic groups — a finding that differs from earlier studies suggesting racial and ethnic disparities in treatment.
“We think the findings that initial monotherapy selection is for the most part being done, is encouraging,” she said. “However, the initial prescribing physician and their team should focus more attention to issues of continuity of care, such as follow-up with patients and families, [to see] whether prescriptions are being filled and whether these patients are getting [the right] follow-up medical care.”
STUDY DESIGN, FINDINGS
The researchers conducted a retrospective analysis of administrative claims from the Centers for Medicare and Medicaid services filed by Medicare beneficiaries aged 67 and older between 2008 and 2010; the claims for a 5 percent random sample of beneficiaries were augmented to increase representation of minority groups with seizures or epilepsy, including African-Americans, Hispanics, Asians, and American Indians.
All beneficiaries included in the analysis had been diagnosed with epilepsy, had two seizures at least 30 days apart, and/or had at least a 60-day prescription for an AED. To ensure all cases of epilepsy were new-onset, the researchers included only patients who had a clean period of at least one year before the index event.
The researchers identified all brand name and generic AED prescriptions filled and examined AED utilization according to racial and ethnic groups. They also calculated time from the index event to the first AED prescription.
During the two-year period, nearly 95 percent of the 3,706 new epilepsy cases identified were given initial monotherapy AED treatment, and 79.6 percent of patients were prescribed one AED only over the follow-up period. Levetiracetam, a newer AED, was the most commonly prescribed in the two samples, given to 45.5 percent of patients. However, phenytoin, an older AED, was the second most commonly prescribed, given to 30.6 percent of patients. Only 50 percent of patients received prompt treatment within 30 days of the index event.
After factoring in potential confounders like race/ethnicity, gender, and age at index event, the researchers found that race/ethnicity was not significantly associated with AED patterns, monotherapy use, or prompt treatment. The analysis also revealed that women (OR 1.20, 95% CI 1.04-1.39), beneficiaries who had a neurologist visit close to the index event (OR 2.10, 95% CI 1.79-2.46), and patients whose index event occurred in the emergency department (OR 1.85, 95% CI 1.60-2.12) were more likely to start an AED within 30 days, while beneficiaries 85 or older were less likely to start an AED within 30 days compared to those between 67 and 74 years old.
A newer AED (levetiracetam) was most commonly prescribed, the researchers found, but phenytoin was nonetheless still prescribed over 30 percent of the time. And although there were no disparities in treatment among ethnic groups, half of patients experienced delayed treatment.
The authors attributed the use of phenytoin, in part, to physicians' reluctance to embrace an unfamiliar medication. “It may be that many physicians are comfortably using older line AEDs given their personal experience with the medication,” Dr. Pisu said.
Mary Jo Pugh, PhD, RN, professor of epidemiology and biostatistics at the University of Texas Health Science Center at San Antonio, agreed that a lack of familiarity with newer AEDs among non-specialists treating a first seizure, including emergency room and general-practice physicians, may be to blame for the continuing popularity of phenytoin.
Dr. Pugh, who led the 10-member panel of epilepsy experts that created epilepsy measures in 2007, said: “Our qualitative data from interviews with geriatricians, primary care providers and neurologists found that [compared to neurologists], primary care providers and geriatricians are not comfortable starting an AED or switching an AED that is already started elsewhere unless it is something they are familiar with. Most are familiar with phenytoin.”
Gregory K. Bergey, MD, FAAN, professor of neurology at Johns Hopkins University and director of the Johns Hopkins Epilepsy Center, noted that given its unfavorable side-effects profile, the continued use of phenytoin is a particularly troubling for this patient subpopulation.
“Phenytoin has many drug interactions – it contributes to mineral density loss and can have toxicity which lead to unsteadiness and may go unappreciated in, say, a 75-year-old who may be unsteady already. If you're taking cholesterol medications, your cholesterol may go up. It's not one of my first five drugs.”
In addition to levetiracetam, which is “easy to use,” Dr. Bergey said, “a number of other newer agents have very favorable side effect profiles that are not being used that much, like lacosamide.”
“This is a very important subgroup of patients because they have symptomatic seizures, they always need long-term therapy, and in many instances, they have comorbidities like high cholesterol and high blood pressure. They may be on an average of six or seven other medications,” Dr. Bergey said. “For them, the choice of medicine is more important than for an eight-year-old who may only take medication for two or three years.”
So why do physicians continue to prescribe phenytoin? Cost is likely an important factor, Dr. Pisu noted. “The lower cost of older drugs may also play a role, especially within lower socioeconomic groups.”
Dr. Bergey agreed, adding that the persistence of phenytoin prescriptions may be due to drug pricing – in particular to Medicare's so-called “donut hole” of coverage.
“In Medicare part D, if you have high but not super-high costs, you can get caught in this donut where you have to pay a high percentage of medical costs,” Dr. Bergey noted. “Patients in that donut may be less likely to want to pay for seizure medicines like levetiracetam or lamotrigine.”
Dr. Pugh agreed, noting that even after the researchers controlled for neurology care close to the index event, “individuals without insurance or in the ‘donut hole’ were still significantly less likely to receive medications within 30 days. This suggests that the biggest factor for timely medication treatment is insurance and financial issues.”
“I would say, we as treating physicians need to be sensitive of the donut and choose appropriate generics,” Dr. Bergey said. “Levetiracetam is available generically. Lamotrigine is very easy to make generically. So I'm disappointed that lamotrigine was used only occasionally. It's a very good drug for the elderly: It's well tolerated, and it's a long-term agent. What would I like to see in five years? More lamotrigine.”
As for the researchers' methodology, “This was a rigorous and appropriate study,” Dr. Bergey said. “It's retrospective, but that's the nature [of a Medicare claims study]. There was a good assessment of male and female differences and racial differences.”
“Many patients will be controlled on monotherapy, so it was very reassuring to see that [so many patients started on just one AED],” Dr. Bergey commented. “There was a little bit of concern about the promptness of AED treatment. But it can be tough to establish a diagnosis sometimes. If they're complex partial seizures, they may be challenging to diagnose, particularly if the patient is over 85, is intellectually compromised due to dementia, or has another condition. Latency to onset of medication may not compromise quality of life. Some of that delay is not all that concerning.”
However, Dr. Bergey noted, “What they didn't ferret out was, were neurologists or primary care prescribing phenytoin? Many older patients have an established primary care relationship that many 20-year-olds [with epilepsy] do not. I would have liked to see whether phenytoin was being used by primary care doctors or neurologists. Then you can address that group as far as education goes.”
Dr. Pugh agreed, adding that improved education about seizure medication among non-epilepsy specialists — who may see older patients with a first seizure far more often than specialists — may be crucial. “Increasing understanding of the differential presentation of seizures in the elderly among geriatricians and primary care providers may be needed to get a more rapid diagnosis and treatment,” she said.