https://www.medpagetoday.com/neurology/seizures/72217
People with epilepsy are three times more likely to die from unnatural causes than people without the disease, an observational study from England and Wales found.
Although the absolute risk of death was low at 0.3% to 0.5%, epilepsy patients were twice as likely to die by suicide, 3.5 times as likely to die by intentional self-poisoning with medication, and five times more likely to die of unintentional medication poisoning, reported Hayley Gorton, PhD, of the University of Manchester in the U.K., and colleagues in JAMA Neurology.
"It was already known that people with epilepsy are at a higher risk of death than those without epilepsy, but we didn't know much about the risks of different types of death, including unnatural death -- mainly accident and suicide," Gorton told MedPage Today.
Most previous research used secondary care data, which may have included mainly patients with severe disease, Gorton added: "In this study, we used primary care data to represent the whole spectrum of people with epilepsy."
While earlier analyses focused on sudden unexpected death in epilepsy (SUDEP), a recent call for action and epidemiological studies identified that mortality among epilepsy patients is not well understood.
For this study, the researchers studied two electronic primary care data sets linked to hospitalization and mortality records: the Clinical Practice Research Datalink (CPRD) in England from 1998 to 2014, and the Secure Anonymised Information Linkage (SAIL) Databank in Wales from 2001 to 2014. The epilepsy index date was defined as the latest date in which a person had received both an epilepsy diagnostic code and an antiepileptic drug prescription.
Gorton et al identified 44,678 epilepsy patients in the CPRD and 14,051 epilepsy patients in the SAIL Databank, matching them by age and sex to 891,429 (CPRD) and 279,365 (SAIL) comparators. In both groups, 51% of the epilepsy and comparison cohorts were male. The median age at entry was 40 in the CPRD groups and 43 in the SAIL groups.
Overall, people with epilepsy were significantly more likely to die of any unnatural cause (HR 2.77), unintentional injury or poisoning (HR 2.97), or suicide (HR 2.15) than people in the comparison groups.
Epilepsy patients had a particularly high risk of unintentional medication poisoning (HR 4.99) and intentional self-poisoning with medication (HR 3.55). Opioids (56.5%) and psychotropic medication (32.3%) were used more commonly than antiepileptic drugs (9.7%) in poisoning deaths.
Some of these causes present a tractable opportunity to reduce overall epilepsy mortality because, unlike SUDEP, they have proven public health, medical, or rehabilitation techniques to prevent them, observed Orrin Devinsky, MD, of New York University and co-authors in an accompanying editorial.
"Among the 11 comorbid neuropsychiatric diagnoses surveyed by Gorton and colleagues, patients with epilepsy exceeded population controls in all but comorbid neuropathic pain." Alcohol and other substance abuse and schizophrenia were more than three times more common among epilepsy patients; bipolar depression, personality disorder, and self-harm were more than twice as common. Depression and anxiety also were 1.5 times higher among people with epilepsy.
Clinical neurologists might identify some of these disorders, but often they are unrecognized and untreated, Devinsky and colleagues noted. And spotting other psychiatric problems that shorten lifespan, like substance abuse or schizophrenia, is more difficult because these patients often do not show up in outpatient clinics.
"These disorders often pull people down socially and away from their families as well as neurologic care," the editorial stated. "We may see them in emergency departments after a bad seizure, but they often fail to show for outpatient follow-up; they are lost from our view and our awareness. They often reappear in public clinics, where neurologists are strapped for time and resources and where access to psychiatric care is limited or nonexistent."
Mood disorder, poor judgment, impulsive behavior, and cognitive impairment may be part of the disease biology, just as brainstem cardiopulmonary dysfunction is thought to contribute to SUDEP, Devinsky et al noted: "Our basic science, epidemiologic, and clinical researchers need to explore the tangled thicket where neurology and psychiatry meet. The National Institutes of Mental Health and Neurological Disorders and Stroke should encourage researchers to explore this overlap and develop effective therapies."
Until then, neurologists can look for ways to reduce epilepsy mortality, Devinsky told MedPage Today. "Clinicians now have data that can empower them and their patients to reduce the risk of SUDEP by improving seizure control, especially control of tonic-clonic seizures.
"We can define high-risk patients -- those with poorly controlled convulsive seizures or nonadherence to antiseizure medicines -- and high-risk settings -- sleeping alone or unsupervised -- to help patients adopt preventive strategies, like phone apps to remind patients to take their medications or seizure-detection monitors to alarm others in their home," he added.
Gorton and colleagues noted several limitations to their research: The data sets used were not generated primarily for the purpose of conducting research, so residual confounding may be present. Coroners may have misclassified some suicides, although the researchers accounted for this by including unnatural deaths of undetermined intent in their suicide definition. And some estimates had low precision due to low event counts for the rarest cause-specific mortality outcomes.
This study was funded by a grant from the National Institute for Health Research.
The researchers reported having no conflicts of interest.
Devinsky reported financial relationships with GW Pharmaceuticals, Novartis, PTC Therapeutics, Zogenix, Pairnomix, Rettco, Tilray, Empatica, and Egg Rock.
- Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner
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Primary Source
JAMA Neurology
Source Reference: Gorton H, et al "Risk of unnatural mortality in people with epilepsy" JAMA Neurology 2018; DOI:10.1001/jamaneurol.2018.0333.Secondary Source
JAMA Neurology
Source Reference: Devinsky O, et al "Deaths in epilepsy: What we are missing" JAMA Neurology 2018; DOI:10.1001/jamaneurol.2018.0002.
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