| Epilepsy  

Premature mortality and epilepsy

Recent insights into premature mortality in epilepsy and potential mitigating factors

People with epilepsy are at increased risk of premature mortality[1] but the underlying reasons are not fully explored.  In a recent retrospective cohort study of 33,615,037 adults aged 65 years or older,[2]* 99,990 subjects who developed epilepsy had a mortality rate of 62.8% over five years.  Epilepsy was particularly associated with higher mortality when diagnosed following another neurological disorder, e.g. multiple sclerosis (adjusted hazards ratio (AHR) 2.13), traumatic brain injury (AHR 1.55) and Parkinson’s disease (AHR 1.29).

Sudden unexpected death in epilepsy (SUDEP) is an important cause of epilepsy-related death.  In a prospective open-label study of adults with drug-resistant focal-onset epilepsy, Nair et al.[3]** report on nine years of patient follow-up after implantation with brain-responsive neurostimulation.  On average, participants had epilepsy for 20 years, were prescribed 2.9 antiseizure medications (ASMs) and experienced 50.7 disabling seizures per month at baseline.  Among 256 patients, there were 16 deaths, six of which were probable or definite SUDEP.  The median seizure reduction was 75%, the responder rate was 73%, and the clinical response improved over time.  The SUDEP rate of 3.2 per 1,000 patient-implantation years was lower than two comparators (9.3 per 1,000 patient-years for epilepsy surgery candidates and 6.9 per 1,000 patient-years for DRE patients in a placebo arm of a randomised controlled ASM trial). 

Sveinsson and colleagues[4]* conducted a population-based case-control study to assess the association between various prescribed drugs and SUDEP among 255 SUDEP cases and 1,148 people with epilepsy as matched controls.  After adjusting for generalised tonic-clonic seizures, ASM polypharmacy was associated with a reduction in SUDEP risk by two-thirds.  This finding is difficult to interpret and may reflect confounders such as the involvement of specialist epilepsy services in more difficult-to-treat cases.  People with epilepsy and a history of ASM regimen non-concordance had an increased SUDEP risk.

*Blue/level 5 and **Green/level 4 in the EAN rainbow ranking system of evidence.


Key Points:

  • New-onset epilepsy in older adults may carry an increased risk of premature mortality, particularly with concomitant neurological conditions.
  • Brain-responsive neurostimulation could reduce the long-term risk of SUDEP in some people with drug-resistant focal-onset epilepsy.
  • Sveinsson et al. report ASM polypharmacy is associated with reduced SUDEP risk, whereas failure to take ASMs as prescribed is associated with increased SUDEP risk



Devinsky O, Spruill T, Thurman D, Friedman D. Recognizing and preventing epilepsy-related mortality. Neurology [online serial]. 2016;86:779–786. Accessed at: www.neurology.org/lookup/doi/10.1212/WNL.0000000000002253.

2.        Blank LJ, Acton EK, Willis AW. Predictors of Mortality in Older Adults With Epilepsy. Neurology [online serial]. 2021;96:e93–e101. Accessed at: www.neurology.org/lookup/doi/10.1212/WNL.0000000000011079.

3.        Nair DR, Laxer KD, Weber PB, et al. Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. Neurology [online serial]. 2020;95:e1244–e1256. Accessed at: www.neurology.org/lookup/doi/10.1212/WNL.0000000000010154.

4.        Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T. Pharmacologic treatment and SUDEP risk. Neurology [online serial]. 2020;95:e2509–e2518. Accessed at: www.neurology.org/lookup/doi/10.1212/WNL.0000000000010874.