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Neurology Today:
doi: 10.1097/01.NT.0000434607.33929.60
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Epilepsy Patients at High Risk for Death, Psychiatric Disorders

Fitzgerald, Susan

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ARTICLE IN BRIEF

Investigators reported that people with epilepsy are overall 11.1 times more likely to die prematurely than unaffected persons, 5.5 times more likely to die from non-vehicle accidents, and 3.7 times more likely to die from suicide. Among persons with epilepsy who die from an external cause, three-quarters of the cases involve a psychiatric diagnosis.

People with epilepsy are far more likely to die prematurely than people without the disease, and psychiatric comorbidity is a major factor in those early deaths, according to a large population-based study from Sweden.

The study found high rates of psychiatric comorbidity, particularly depression, before and after diagnosis of epilepsy, as well as a high incidence of substance misuse among persons with epilepsy; both of those factors contributed to an increased risk of death due to suicide or non-vehicle accident.

The study, published ahead of print in the July 19 online edition of The Lancet, found that people with epilepsy are overall 11.1 times more likely to die prematurely than unaffected persons, 5.5 times more likely to die from non-vehicle accidents, and 3.7 times more likely to die from suicide. Among persons with epilepsy who die from an external cause, three-quarters of the cases involve a psychiatric diagnosis, the investigators found.

“The findings underscore the importance of identifying psychiatric disorders in patients at the time of epilepsy diagnosis and during follow-up, and having services in place to effectively treat any comorbid conditions,” the lead study author Seena Fazel, MD, a Wellcome Trust senior research fellow in clinical medicine at Oxford University in England, told Neurology Today in an e-mail message. “There may also be a role for increased monitoring of high-risk subgroups, such as individuals in the first six months after diagnosis of epilepsy.”

Andres Kanner, MD — director of the International Comprehensive Epilepsy Center and chief of the Epilepsy Division at the University of Miami Miller School of Medicine — said that while it's been known that people with epilepsy are at elevated risk for depression and suicide, as well as sudden unexplained death, the new study provided additional data that helped estimate the magnitude of the risks.

“In addition, this study provided new epidemiologic data on the increased risk of substance abuse in people with epilepsy that may also contribute to an increased mortality risk,” said Dr. Kanner, who was not involved with the study. “Sadly, psychiatric problems often go unrecognized in persons with epilepsy. This is an important study because it highlights the role that comorbid psychiatric conditions play in the risk for premature mortality.”

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SWEDISH REGISTRIES USED

The study drew on the extensive health records-databases that exist in Sweden, which has a single-payer health care system. The research team linked data from several longitudinal nationwide population registers, including the National Patient Registry and the Cause-of-Death registry, to identify 69,995 persons who were born between 1954 and 2009 and who had an inpatient or outpatient diagnosis of epilepsy. They were then compared with 660,869 age-matched and sex-matched people in the general population and 81,396 unaffected siblings.

The study did not include older people because its focus was premature death. The inclusion of unaffected siblings as controls helped researchers sort out whether epilepsy patients' premature deaths and comorbidities might be due to familial factors — genetic or environmental — rather than the disease itself. Study participants were tracked for an average of nine years. [See “Study Data: Premature Morbidity and Epilepsy.”]

The researchers noted that while the study involved only Sweden, the findings are likely applicable to other high-income countries as well.

Rates of psychiatric illness and substance misuse were higher for epilepsy patients both before and after diagnosis compared with controls — a finding that supports the belief that people with epilepsy don't suffer from depression or other psychiatric conditions merely because they feel depressed or anxious because they have been diagnosed with epilepsy.

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ATTENTION MUST BE PAID

Gregory Holmes, MD, professor of neurological sciences and pediatrics and chair of the department of neurological sciences at the University of Vermont, told Neurology Today that the study's findings should be a reminder to physicians that controlling seizures is just part of the equation for optimizing the well-being of epilepsy patients.

“Epilepsy is a brain disorder so it is not surprising that along with epilepsy you have other brain disorders,” Dr. Holmes said. Neurologists and others caring for epilepsy patients need to connect them with psychiatric services in the community because a single clinician usually can't meet every single need of a patient, he said. “We have to guide patients and their families to the treatments they need,” he added.

Selim Benbadis, MD, professor of neurology and director of the Comprehensive Epilepsy Program at the University of South Florida and Tampa General Hospital, said there is a growing consensus that epilepsy and other psychiatric conditions often “travel together.”

“We don't want to be alarmist to patients,” Dr. Benbadis said. “Still, the message here is that we can't be complacent.” He said patients need to know that while epilepsy is medically controllable in the majority of cases, “epilepsy is not a benign disease.”

Clinicians should pay particular attention to quality-of-life issues in patients whose seizures are not well controlled by medications, he added.

Lawrence Brown, MD, an epileptologist and director of the pediatric neuropsychiatry program at The Children's Hospital of Philadelphia, said researchers have focused a lot on the issue of sudden unexplained death in epilepsy, “but this study goes beyond that and says ‘it’s also the accidents and also the suicides that are a concern,'” he said. At the same time, he added, “clinicians face the challenge of deciding how much potentially alarming information to give patients and their families and when.”

“We don't generally start out when someone first develops seizures by saying 'Your child has an increased risk of doing poorly in school, having social disabilities, being depressed, having suicidal thoughts, and having sudden unexplained death,'” Dr. Brown said. “However, we are at increased surveillance and we try to address those issues before they become problems,” said Dr. Brown, associate professor of neurology and pediatrics at the Perelman School of Medicine at the University of Pennsylvania.

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It is especially important to educate teenagers who are soon off to college and on their own that not only do they need to take their medicine every day, but they also need to make good choices and pay attention to their mental health, he said.

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STUDY DATA: PREMATURE MORBIDITY AND EPILEPSY

Among the study findings:

* 8.8 percent of people with epilepsy died by the end of the follow-up period, compared with 0.7 percent of the controls.

* 40.7 percent of those with epilepsy had a psychiatric diagnosis at any point during their lifetime, compared with 10.3 percent of controls.

* 8.9 percent of those with epilepsy had a lifetime diagnosis of depression, compared with 3.3 percent of controls.

* 11.5 percent of epilepsy patients had a lifetime diagnosis of substance misuse (drugs, alcohol), compared with 2.9 percent of controls.

* 15.8 percent of all epilepsy deaths were from external causes, including non-vehicle accident and suicide. Of those who died from an external cause, 75.2 percent had comorbid psychiatric conditions, in particular depression or substance misuse.

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LINK UP FOR MORE INFORMATION:

•. Fazel S, Wolf A, Långström N, et al. Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study. Lancet 2013; E-pub 2013 Jul 19.
•. Neligan A, Bell GS, Johnson AL, et al. The long-term risk of premature mortality in people with epilepsy. Brain 2011;134 (2): 388–395.

•. Neurology archive of epilepsy and its comorbidities: http://bit.ly/1ctFyzp.

© 2013 American Academy of Neurology

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