Investigators reported that children with epilepsy who were from homes in which the caregivers or parents had lower-status jobs (such as gardeners, welfare service aids, and production inspectors) were less likely to take their medications as directed.
In children with newly diagnosed epilepsy, the most significant factor that predicted adherence to a therapeutic regimen was socioeconomic status. Children from homes in which the caregivers or parents had lower-status jobs (such as gardeners, welfare service aides, and production inspectors) were less likely to take their medications as directed, according to a new study published in the April 27 Journal of the American Medical Association (JAMA).
Of particular concern, investigators noted, is that 58 percent of the 124 children, ages 2 to 12, who were seen at the New Onset Seizure Clinic at Cincinnati Children's Hospital Medical Center in Ohio, did not comply with their medication regimen in the first six months of treatment.
“This is the first study to examine patterns of adherence for children with newly-diagnosed epilepsy, and we were quite surprised by the level of non-adherence exhibited this early in the course of therapy,” said the lead study author, Avani C. Modi, MD, assistant professor in the Division of Behavioral Medicine and Clinical Psychology at Cincinnati Children's Hospital, in an e-mail to Neurology Today.
“We examined several other factors [besides socioeconomic status], including child sex, child age, caregiver marital status, who observed the first seizure, side effects, seizure type, and number of drugs prescribed — none of which differentiated the groups,” said Dr. Modi.
The findings suggest a need for intervention studies that aim to optimize adherence early in the course of the therapy, she and co-investigators wrote.
Dr. Modi said the investigators next plan to look at psychosocial factors, such as child behavior and mood, family functioning, epilepsy knowledge, and parenting stress, as potential factors that affect adherence. “Because our study is longitudinal, we plan to examine how these psychosocial variables change over time and how this influences adherence over time.”
The data on adherence were collected between April 2006 and 2009. The parents or primary caregivers of the children filled out a detailed demographics questionnaire including questions about the child's age, sex, race/ethnicity, as well as the caregivers' medical status, level of education, and occupation (status).
To track medication use, they were given a bottle and cap, which had an electronic monitoring system — a microchip — to track dates and times when the bottle was opened or closed. The microchip stored the data, which was then downloaded to a Windows-based computer for analysis. Daily adherence was measured on a 0 percent, 50 percent, or 100 percent scale, as drugs were taken twice daily. About one month after diagnosis, and every three months subsequently, patients returned to the clinic for follow-up.
Sixty percent of participants were initially prescribed the drug carbamazepine and 40 percent were prescribed valproic acid. No participants had prolonged seizures or experienced status epilepticus during the study period.
DR. ORRIN DEVINSKY said that further studies should now focus on compliance strategies for lower socioeconomic status families that incorporate greater education and awareness of the importance of regular medication use, as well as the risks of ongoing seizures to health, cognition, and behavior.
“Overall, approximately 60 percent of children with epilepsy and their families exhibited some level of non-adherence, and we found five distinct patterns of adherence over time,” said Dr. Modi — from those who had near-perfect adherence and rarely missed doses during the entire six-month period to children who missed doses regularly. For instance, patients in the lower adherence group (severe delayed nonadherence) were missing, on average, half their doses over the six month period, such that they only took 180 of the 360 doses they should have taken. (See “Patterns of Adherence,” for more information.)
The researchers found that patients and families who mostly took their drugs as scheduled — that is, they followed their regimen about 97 percent of the time — came from families with higher-status jobs than the families in the bottom three adherence groups. Families in the mild to moderate nonadherence groups adhered, on average, 67 to 85 percent of the time; occupations for caregivers in these two groups included engineering technicians, legal assistants, farmers, and inventory clerks. Caregivers of both the severe non–adherence groups — with adherence ranging from an average of 6 percent to 49 percent, held occupations such as gardeners, account collectors, and production inspectors.
DR. AVANI C. MODI: “This is the first study to examine patterns of adherence for children with newly-diagnosed epilepsy, and we were quite surprised by the level of non-adherence exhibited this early in the course of therapy.”
Several epileptologists who were not involved with the study praised the work of the investigators. “I believe issues like this have been neglected for far too long, and I applaud Dr. Modi, and colleagues, for bringing this to national attention,” Douglas R. Nordli Jr., MD, division head of the Epilepsy Center at Children's Memorial Hospital in Chicago, said.
But some experts raised questions about the study design, noting that there were other data that might be helpful to glean from such an analysis. Orrin Devinsky, MD, professor of neurology and director of the Comprehensive Epilepsy Center at New York University Langone Medical Center, speculated, for example, that how neurologists communicate to patients of different socioeconomic sectors might affect their compliance to therapy. And James W. Wheless, MD, professor and chief of the department of pediatric neurology at the University of Tennessee Health Science Center, thought the emotional state and cognitive status of the caregivers might influence the results.
“What if the mom's depressed?” Dr. Wheless asked. “They didn't look at any scale of maternal or parent anxiety or depression — and we know that has a huge influence on whether they are going to give their kids medicine, their understanding of the disease, or even just their caring of the kids.”
Dr. Wheless added: “It may just be that the poor SES [socioeconomic status] means these folks could be reading at a fourth to sixth grade level and maybe didn't even understand what the doctors were telling them.”
Dr. Nordli suggested a social work review might be useful for those families at greatest risk. “Funding for social work resources and mental health issues is critically low and these services are essential for optimal patient care. It does no good to spend thousands of dollars accurately diagnosing epilepsy, doing state-of-the-art clinical neurophysiological studies, performing imaging and providing the most sophisticated and well-trained epileptologists and nurse practitioners if patients are not able to adhere to the treatment,” Dr. Nordli said.
Dr. Devinsky said that further studies should now focus on compliance strategies for lower socioeconomic status families that incorporate greater education and awareness of the importance of regular medication use, as well as the risks of ongoing seizures to health, cognition, and behavior. “Yes, adherence can be improved,” he said, “but the challenge is what are the most effective and efficient strategies?”
Dr. Wheless said it is important to make sure patients and caregivers understand the long-term nature of the illness. “It's very different to take a medicine chronically rather than, say, taking the Z-Pak for a couple of days.” That distinction is not always clear, he said, as sometimes patients will stop taking medication when their prescription runs out, instead of getting a refill.
No adherence interventions have been tested in children with epilepsy yet, Dr. Modi said, and so another important follow-up step would be to assess strategies that have worked in other pediatric chronic conditions.
“We need to identify the level of adherence that is necessary to achieve seizure control,” Dr. Modi said, “and the role non-adherence may play in the course of the disease [in children].”Dr. Modi noted that interventions that focus on problem solving around barriers to adherence are promising, and the investigators have begun testing such interventions for children with newly diagnosed epilepsy.
DR. DOUGAS R. NORDLI JR.: “Funding for social work resources and mental health issues is critically low and these services are essential for optimal patient care. It does no good to spend thousands of dollars accurately diagnosing epilepsy, doing state-of-the-art clinical neurophysiological studies, performing imaging and providing the most sophisticated and well-trained epileptologists and nurse practitioners if patients are not able to adhere to the treatment. “
Meanwhile, clinicians should establish an open dialogue with patients and families about potential barriers to adherence, she said. Dr. Modi suggested working with families to set medication schedules around daily routines and identifying best times of day to take medication, such as during meals or when brushing teeth.
How do you get patients back on track with their medication when they miss their dose? In the past, we used to ask people whether they missed any doses of their medicine, said James Wheless, MD, professor and chief of the department of pediatric neurology at the University of Tennessee Health Science Center. “This is sort of like asking your kids, ‘Did you lie to me yesterday?’ … Every patient is going to say no because they don't want their doctor to think badly of them.”
He and his colleagues have since stopped asking that question. Instead, with new patients, he said he and his nurse now “document what the plan is, based on their medicine, for what they should do when they do miss a dose. Because, as this article nicely addressed, it's only a small subset that was in the group that was adherent nearly all the time.”
Dr. Wheless suggested that having a plan to give sustained-release preparations for seizure medications can be helpful. Unfortunately, this is not always practical for children, he acknowledged, as long-acting preparations often come in the form of pills. Regardless, he said there needs to be a (preferably written) back-up plan in place.