Lamotrigine, levetiracetam effective first-line treatments in post-stroke epilepsy

Researchers observed differences in survival between antiseizure medications in post-stroke epilepsy, with lamotrigine and levetiracetam appearing to be reasonable first-line treatment options, according to a study in JAMA Neurology.

“The association of post-stroke epilepsy (PSE) with mortality varies between studies, but the hazard ratio (HR) of death seems increased on a population level,” David Larsson, MD, of the department of neurology at Sahlgrenska University Hospital in Sweden, and colleagues wrote. “The reason for the increased mortality with PSE is unknown. Potential explanations include detrimental effects from antiseizure medications (ASMs), especially enzyme inducers, which could increase cardiovascular risk and interact with drugs used for secondary stroke prevention.”

However, the researchers noted a lack of population-based real-world data on links between ASMs and mortality among patients with PSE. To address this research gap, analyzed individual-level data from linked registers on all adults in Sweden with acute stroke between July 1, 2005, and Dec. 31, 2010, and subsequent epilepsy onset prior to Dec. 31, 2014. They included 2,577 patients (54% men; median age, 78 years) who received continuous ASM monotherapy. They used Cox proportional hazards regression with carbamazepine as the reference to analyze all-cause death, which served as the primary outcome. Further, they used Fine-Gray competing risk regression models to examine cardiovascular death based on ICD-10 criteria.

Results showed lamotrigine, levetiracetam, valproic acid, phenytoin and oxcarbazepine had adjusted HRs of all-cause death compared with carbamazepine of 0.72 (95% CI, 0.6-0.86), 0.96 (95% CI, 0.8-1.15), 1.4 (95% CI, 1.23-1.59), 1.16 (95% CI, 0.88-1.51) and 1.16 (95% CI, 0.81-1.66), respectively. Larsson and colleagues noted adjusted HRs for cardiovascular death compared with carbamazepine of 0.76 (95% CI, 0.61-0.95) for lamotrigine, 0.77 (95% CI, 0.60-0.99) for levetiracetam, 1.4 (95% CI, 1.19-1.64) for valproic acid, 1.02 (95% CI, 0.71-1.47) for phenytoin and 0.71 (95% CI, 0.42-1.18) for oxcarbazepine.

“Patients treated with lamotrigine had significantly lower mortality than those treated with carbamazepine, whereas patients prescribed valproic acid had an increased risk of both cardiovascular and all-cause death,” the researchers wrote. “Levetiracetam was associated with a reduced risk of cardiovascular death compared with carbamazepine. Altogether, our findings suggest an association between ASM selection and mortality among patients with a history of cerebrovascular disease.”