Key Points
Question What is the
risk and medication contribution to cause-specific unnatural mortality in
people with epilepsy?
Findings In this
population-based cohort study, more than 50 000 people with epilepsy and 1
million matched individuals without epilepsy were identified in 2 data sets
from the general populations of England and Wales. People with epilepsy had a
3-fold increased risk of any unnatural mortality and a 5-fold increased risk of
unintentional medication poisoning; psychotropic and opioid, but not
antiepileptic, drugs were most commonly used in poisoning.
Meaning Clinicians
should provide advice on unintentional injury and poisoning and suicide
prevention and consider the toxicity of concomitant medication when prescribing
drugs for people with epilepsy.
Abstract
Importance People
with epilepsy are at increased risk of mortality, but, to date, the cause-specific
risks of all unnatural causes have not been reported.
Objective To estimate
cause-specific unnatural mortality risks in people with epilepsy and to
identify the medication types involved in poisoning deaths.
Design, Setting, and Participants This population-based cohort study used 2
electronic primary care data sets linked to hospitalization and mortality
records, the Clinical Practice Research Datalink (CPRD) in England (from
January 1, 1998, to March 31, 2014) and the Secure Anonymised Information
Linkage (SAIL) Databank in Wales (from January 1, 2001, to December 31, 2014).
Each person with epilepsy was matched on age (within 2 years), sex, and general
practice with up to 20 individuals without epilepsy. Unnatural mortality was
determined using International Statistical Classification of Diseases and
Related Health Problems, Tenth Revision codes V01 through Y98 in the Office for
National Statistics mortality records. Hazard ratios (HRs) were estimated in each
data set using a stratified Cox proportional hazards model, and meta-analyses
were conducted using DerSimonian and Laird random-effects models. The analysis
was performed from January 5, 2016, to November 16, 2017.
Exposures People with
epilepsy were identified using primary care epilepsy diagnoses and associated
antiepileptic drug prescriptions.
Main Outcomes and Measures
Hazard ratios (HRs) for unnatural mortality and the frequency of each
involved medication type estimated as a percentage of all medication poisoning
deaths.
Results In total,
44 678 individuals in the CPRD and 14 051 individuals in the SAIL Databank were
identified in the prevalent epilepsy cohorts, and 891 429 (CPRD) and 279 365
(SAIL) individuals were identified in the comparison cohorts. In both data
sets, 51% of the epilepsy and comparison cohorts were male, and the median age
at entry was 40 years (interquartile range, 25-60 years) in the CPRD cohorts
and 43 years (interquartile range, 24-64 years) in the SAIL cohorts. People with
epilepsy were significantly more likely to die of any unnatural cause (HR,
2.77; 95% CI, 2.43-3.16), unintentional injury or poisoning (HR, 2.97; 95% CI,
2.54-3.48) or suicide (HR, 2.15; 95% CI, 1.51-3.07) than people in the
comparison cohort. Particularly large risk increases were observed in the
epilepsy cohorts for unintentional medication poisoning (HR, 4.99; 95% CI,
3.22-7.74) and intentional self-poisoning with medication (HR, 3.55; 95% CI,
1.01-12.53). Opioids (56.5% [95% CI, 43.3%-69.0%]) and psychotropic medication
(32.3% [95% CI, 20.9%-45.3%)] were more commonly involved than antiepileptic
drugs (9.7% [95% CI, 3.6%-19.9%]) in poisoning deaths in people with epilepsy.
Conclusions and Relevance
Compared with people without epilepsy, people with epilepsy are at
increased risk of unnatural death and thus should be adequately advised about
unintentional injury prevention and monitored for suicidal ideation, thoughts,
and behaviors. The suitability and toxicity of concomitant medication should be
considered when prescribing for comorbid conditions.
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