Neurology
Choice of first antiseizure drug may influence survival in dementia-related epilepsy
Clinical Takeaway: Consider lamotrigine or levetiracetam over valproate when initiating ASM therapy in patients with dementia and epilepsy, given observed associations with lower mortality risk.
Seizures are increasingly recognized in dementia, but evidence guiding antiseizure medication (ASM) selection is limited—raising concern that drug choice could inadvertently affect survival.
A large Swedish cohort study of 5,764 adults with both dementia and epilepsy found that the choice of first ASM was associated with significant differences in survival.
Over a follow-up spanning 2006 to 2023, valproate use (n=746) was associated with a 34% higher adjusted risk of death compared with other treatments (adjusted hazard ratio [aHR] 1.34; 95% confidence interval [CI], 1.20–1.48). Meanwhile, lamotrigine (n=922) was associated with a 16% lower mortality risk (aHR, 0.84; 95% CI, 0.75–0.93), and levetiracetam (n=2,098) showed no significant increase (aHR, 0.93; 95% CI, 0.85–1.03). Carbamazepine (n=1,578) served as a common historical comparator.
Cardiovascular mortality appeared to drive some of these differences: valproate was associated with increased risk of cardiovascular death vs. carbamazepine (aHR, 1.30; 95% CI, 1.11–1.52), whereas lamotrigine was associated with reduced risk (aHR, 0.79; 95% CI, 0.66–0.94).
Results were consistent across multiple sensitivity analyses, including propensity matching and restricted survival models.
“Use of valproate was associated with the highest risk of death in persons with epilepsy and dementia,” the authors noted, highlighting the potential clinical importance of first-line drug selection.
These findings support prioritizing newer ASMs in this vulnerable population, though randomized trials are needed to establish causality.
Source: Zelano J, et al. (2026, April 17). Neurology. Differences in Survival Associated With the First Antiseizure Medication in People With Dementia and Epilepsy