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For Your Patients-Epilepsy

What Neurologists May Be Missing — The Higher Risk for Suicide, Drug Overdose, for People with Epilepsy

Fitzgerald, Susan

doi: 10.1097/01.NT.0000534161.51910.96
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The absolute risk of unnatural death is quite small — anywhere from 0.3 percent to 0.5 percent, according to new findings, but the study found that people with epilepsy are five times more likely to die because of accidental poisoning from medication and three times more likely to die from an intentional overdose of medication compared to people who don't have epilepsy.

A new study paints a troubling picture of the deadly side of epilepsy, indicating that people with epilepsy may have a higher risk for unnatural deaths compared to healthy people.

Much attention has been focused on sudden unexplained death in epilepsy, but this study underscores the risk that people with epilepsy face from death from suicide, drug overdose, and other unnatural causes.

The absolute risk of unnatural death is quite small — anywhere from 0.3 percent to 0.5 percent — according to the new findings, but the study found that people with epilepsy are five times more likely to die because of accidental poisoning from medication and three times more likely to die from an intentional overdose of medication compared to people who don't have epilepsy.

The findings are based on a large population-based cohort study conducted in the United Kingdom. The results, published in the April 9 online edition of JAMA Neurology, suggest that neurologists and other health care practitioners who treat epilepsy need to pay more attention to comorbid conditions, such as depression, anxiety, and substance abuse, and to better monitor for the various medications, including opioids and psychotropic drugs, that patients may be taking.

An editorial that accompanied the study said the findings “shed light on an enormous problem hiding in plain sight.” Better coordination between neurology and psychiatry is needed, the editorialists wrote, so that patients with epilepsy get the full range of treatment they need.



Hayley C. Gorton, PhD, the study's lead author and research associate at the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester in the UK, told Neurology Today that while it's been known that people with epilepsy are at higher risk of death, “we didn't know much about the risks of different types of death.”

Dr. Gorton said in an email that the results could help inform “prevention, education, and intervention” initiatives.

The study draws its numbers from two large primary-care data sets, the Clinical Practice Research Datalink (CPRD) in England and the Secure Anonymised Information Linkage (SAIL) Databank in Wales. The databases are linked to hospitalization and death records. The researchers matched 44,678 people with epilepsy in the CPRD database to 891,429 people without epilepsy (for the years 1998 to 2014), and 14,051 people with epilepsy in the SAIL database to 279,365 comparison controls (2001 to 2014).

The analysis found that, compared to healthy controls, people with epilepsy were overall 2.77 times more likely to die of an unnatural cause, 2.97 times more likely to die of unintentional injury or poisoning, and 2.15 times as likely to die of suicide.

There was a 4.99 times higher risk for unintentional poisoning with medication and 3.55 times higher risk for intentional medication poisoning. Opioids (56.5 percent) and psychotropic medication (32.3 percent) were more often involved in cases of medication poisoning deaths in people with epilepsy than antiepileptic drugs (9.7 percent).

The study concluded that patients “should be adequately advised about unintentional injury prevention and monitored for suicidal ideation, thoughts and behaviors.” In addition, the study authors wrote, “the suitability and toxicity of concomitant medication should be considered when prescribing for comorbid conditions.”

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Elizabeth Donner, MD, director of the Comprehensive Epilepsy Program at the Hospital for Sick Children in Toronto, said the new study provides important information.

The potential for “sudden unexplained death has gotten a lot more attention” from researchers and clinicians, she told Neurology Today, while “the other areas of increased mortality in people with epilepsy have not been properly addressed or been given proper attention.”

She said that having good seizure control does not mean that a patient with epilepsy is otherwise trouble free or experiencing a good quality of life.

“There is a risk with focusing only on seizure control because it may ignore other aspects of a chronic illness,” said Dr. Donner, associate professor in pediatrics at University of Toronto. She said neurologists and others who care for people with epilepsy should screen for psychiatric and behavioral health issues and strive to connect patients with the appropriate specialists and resources.

Patient education is key, too. While it may be uncomfortable for doctors to talk with patients and families about the elevated risk for mental health problems, “we should not underestimate or disregard that many people with epilepsy have comorbidities that may result in unnatural mortality and life challenges,” Dr. Donner said.

Dr. Donner said she tries to be balanced in what she tells patients. “I don't want it to be either scary or hopeful. I want it to be informing,” she said.

Dr. Donner said the full extent of epilepsy-related mortality may not be realized because a death certificate may not list epilepsy as a contributing cause of death if a person dies, for instance, from suicide or drug overdose. She recently coauthored a position paper for the National Association of Medication Examiners with recommendations aimed to improve reporting on epilepsy-related deaths. The paper was published in the March issue of Epilepsia.

Hamada Hamid Altalib, DO, MPH, FAES, co-director of the Epilepsy Center of Excellence at the Connecticut VA Healthcare System, said that although previous studies have shown a link between epilepsy and unnatural death, the new study is impressive because it involves very large datasets that reflect the general public, not just a select sampling of patients, such as the elderly or veterans.

He said the fact that people with epilepsy are much more likely to die from unnatural causes such as suicide or drug overdose speaks in large part to shortcomings in the health care system, which often makes it hard for patients to get ready access to mental health services, in some cases because insurance won't pay for it.

“A fundamental problem is how do we (neurologists) integrate and collaborate with mental health?” said Dr. Altalib, assistant professor at Yale School of Medicine who is board certified in both neurology and psychiatry.

He said he trains residents to routinely ask people with epilepsy about depression and other mental health concerns even if they seem perfectly fine, asking questions such as “Have you ever thought about killing yourself?'”

“We should be warning patients that people with epilepsy are at higher risk from dying from suicide, from dying of sudden death,” he said. He said patients should not only be connected with mental health professionals but also be given information on emergency services like crisis hotlines and prevention centers. “We should be very cautious about suicidality,” he added.

Dr. Altalib also stressed that while getting good seizure control is important for optimizing mental health, it isn't the end-all. He said he was involved in a study of people who had undergone epilepsy surgery that found that even those with a positive outcome had an elevated risk for suicide.

Why epilepsy puts people at higher risk for suicide isn't fully understood, he said.

The accompanying editorial in JAMA Neurology, coauthored by Orrin Devinsky, MD, FAAN, and others at NYU Langone Medical Center, said there may be more sympathy for a person who dies from sudden, unexplained death as opposed to “a middle-aged man with epilepsy who does not adhere to the prescribed treatment, experiences depression and alcohol and opioid use disorders, and dies of an overdose.” But they said that needs to change.

“Our basic science, epidemiologic, and clinical researchers need to explore the tangled thicket where neurology and psychiatry meet,” the editorialists wrote. “We need to recognize the gaps in our health care and research and work diligently to close them.”

Dr. Devinsky told Neurology Today in an email that the issue of unnatural premature deaths in epilepsy is “an urgent and under-recognized problem.” He said doctors can help reduce risks by prescribing “the most effective medications with a schedule that patients can adhere to and that maximizes seizure control and minimizes side effects.” In addition, monitoring patients for other drugs they are using and “educating them about lifestyle factors such as sleep hygiene, avoiding alcohol, etc.” is important, as is connecting patients with psychiatric care if warranted.

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•. Gorton HC, Webb RT, Carr MJ, et al Risk of unnatural mortality in people with epilepsy JAMA Neurol 2018; Epub 2018 Apr 9.
    •. Devinsky O, Singh A, Friedman D. Editorial: Deaths in epilepsy, what we are missing JAMA Neurol 2018; Epub 2018 Apr 9.
      •. Middleton O, Atherton D, Bundock E, et al National Association of Medical Examiners position paper: Recommendations for the investigation and certification of deaths in people with epilepsy Epilepsia 2018; 59(3):530–543.
      © 2018 American Academy of Neurology