Epilepsy Linked to Increased Death From Accidents, Suicide

April 16, 2018

People with epilepsy are twice as likely to die by suicide and three times more likely to die accidentally compared with the general population, a new large-scale cohort study shows.

The study also found that people with epilepsy were five times more likely to die specifically by accidental medication poisoning and three and a half times more likely to die by intentional medication poisoning.

Opioid painkillers and medicines for psychiatric illness were most commonly taken in fatal poisonings among people with and without epilepsy, whereas fatal overdoses involving antiepileptic drugs were comparatively rare.

"Although the risks of dying unnaturally for people with epilepsy are low in absolute terms (0.3% to 0.5%), they are higher than in people without epilepsy," lead author, Hayley Gorton, PhD, University of Manchester, United Kingdom, commented to Medscape Medical News.

"Physicians need to be more aware of the risks, especially when prescribing medication for comorbid mental health conditions in these patients," she added. "And patients should be warned about the increased risk of unintentional injury, advised on prevention strategies and monitored for suicidal ideation, thoughts, and behaviors."   

The study was published online in JAMA Neurology on April 9.

The researchers, from the University of Manchester and the University of Swansea, United Kingdom, say that to their knowledge, this is the first study to comprehensively examine cause-specific unnatural mortality risks, including both unintentional and intentional medication poisoning separately, in people with epilepsy.

Focus on Psychiatric Comorbidities

Lead author of an accompanying editorial, Orrin Devinsky, MD,  NYU Langone Medical Center, New York City, told Medscape Medical News that it is known that people with epilepsy have an increased risk for sudden death compared with the general population, including sudden unexpected death in epilepsy (SUDEP), but this paper highlights that individuals with epilepsy are also at much greater risk for unnatural deaths.   

"Undoubtedly some of the deaths in this study would have been due to SUDEP, but we can't tell how many from this data," Devinsky said. "But it does show that the combination of psychiatric disease and psychiatric medication makes a significant contribution to deaths in people with epilepsy."  

"This study reinforces that patients who have a psychiatric condition as well as epilepsy — which is not uncommon — have a dramatically increased risk of dying, and it suggests that accidental overdose with opiates is a more frequent cause of death in this population than has been recognized before," he added. "We therefore need to be careful with prescribing such medication and make sure we counsel patients thoroughly about the risks."

For the study, Gorton and colleagues analyzed data from two UK primary care datasets linked to hospitalization and mortality records from 1998 to 2014.

Each person with epilepsy was matched on age, sex, and general practice with up to 20 individuals without epilepsy.  Mortality and cause of death were determined from the UK Office for National Statistics records.

In total, 58,729 individuals in the two datasets were identified as having epilepsy, and they were matched with 1,170,794 controls. The median age at entry in the epilepsy cohort was 40 years in one dataset and 43 in the other.

Results showed that people with epilepsy were significantly more likely to die of any unnatural cause (hazard ratio [HR], 2.77), unintentional injury or poisoning (HR, 2.97), or suicide (HR, 2.15) than people in the comparison cohort.

Risk increases were particularly large in the epilepsy cohorts for unintentional medication poisoning (HR, 4.99) and intentional self-poisoning with medication (HR, 3.55).

Opioids (56.5%) and psychotropic medication (32.3%) were more commonly involved than antiepileptic drugs (9.7%) in poisoning deaths in people with epilepsy.

The researchers note that the reasons for the increased risk for unintended death may include the direct consequences of seizures or may be unassociated with epilepsy. They point out that the mental illness comorbidities associated with epilepsy are also associated with increased risk for unintentional injury, poisoning, and suicide, and mental health diagnoses were more common in the epilepsy cohort than controls in this study.

"Clinicians should explore any symptoms of mental illness in people with epilepsy and ask about suicidal thoughts," they write.

The psychosocial impact and stigma surrounding epilepsy may also contribute to the increased risk for unnatural death, they add.

Gaps in Care  

In the editorial, Devinsky and colleagues say that the deaths reported in this analysis present "a more tractable opportunity to reduce overall epilepsy mortality in the near future because, unlike SUDEP, there are proven public health, medical, or rehabilitative techniques available for prevention."

They point out that psychiatric disorders were much more common in the individuals with epilepsy than controls: Alcohol/substance abuse and schizophrenia were more than 3-fold more common; bipolar depression, personality disorder, and self-harm were more than 2-fold more common; and depression and anxiety were about 1.5-fold higher.

They suggest this likely contributed to the increased risk for unnatural death and call for more efforts to identify these patients and ensure they get the treatment they need. But they note that patients with psychiatric disorders are far less likely to access medical care; rather, they " sink in social class and disappear from the sight of most physicians."

"Mood disorders, poor judgment, impulsive behavior, and cognitive impairment that contribute to…premature death" in people with epilepsy "are part of the disease biology as much as brain stem cardiopulmonary dysfunction is thought to contribute to SUDEP," the editorialists conclude. "Our basic science, epidemiologic, and clinical researchers need to explore the tangled thicket where neurology and psychiatry meet….  We need to recognize the gaps in our health care and research and work diligently to close them. "

This study was funded by the UK National Institute for Health Research and Health and Care Research Wales.

JAMA Neurol. Published online April 9, 2018. Full text, Editorial

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