Lamotrigine and levetiracetam reasonable first-line treatment options for patients with poststroke epilepsy: JAMA

Sweden: Recent research found disparities in survival among individuals treated with various antiseizure medications (ASM) for poststroke epilepsy. The findings of this study were published in the Journal of American Medical Association - Neurology.

The study further showed that the patients who received lamotrigine monotherapy had lower mortality compared to those receiving carbamazepine. However, prescribed who were prescribed valproic acid had a higher risk of cardiovascular and all-cause death. Levetiracetam was tied to a lower risk of cardiovascular death compared with carbamazepine, but there was no significant difference in overall mortality. 

There is little information to advise the selection of antiseizure medicine for people suffering from poststroke epilepsy. There are theoretical concerns about the negative effects of ASMs on survival. Secondary stroke prophylaxis may be hampered by enzyme-inducing medications. The US Food and Drug Administration has published a safety alert regarding lamotrigine's suspected proarrhythmic characteristics. As a result, David Larsson and his colleagues did this research. To see if mortality differs with certain ASMs in individuals with poststroke epilepsy.

Cohort research was carried out utilizing individual-level data from linked registries on all persons in Sweden who suffered an ischemic stroke between July 1, 2005, and December 31, 2010, and then developed epilepsy before December 31, 2014. The trial included 2577 individuals who were undergoing continuous ASM monotherapy. Between May 27, 2019, and April 8, 2021, data was evaluated. The exposure status was established by the dispensed ASM, and the initial dispensing date signified the commencement of therapy. Cox proportional hazards regression was used to examine the primary outcome, all-cause mortality, with carbamazepine as the reference. Fine-Gray competing risk regression models were used to assess cardiovascular mortality.

The key findings of this study were as follow:

1. A total of 2577 patients were enrolled in the study.

2. When compared to carbamazepine, the adjusted hazard ratio for all-cause mortality was 0.96 for levetiracetam, 0.72 for lamotrigine, 1.40 for valproic acid, 1.16 for oxcarbazepine, and 1.16 for phenytoin. 

3. When compared to carbamazepine, the adjusted hazard ratio for cardiovascular mortality was 0.77 for levetiracetam, 0.76 for lamotrigine, 1.40 for valproic acid, 0.71 for oxcarbazepine, and 1.02 for phenytoin. 

In conclusion, Patients who received lamotrigine alone had a considerably lower death rate than those who received carbamazepine. The converse was true for valproic acid patients, who had a greater risk of cardiovascular and all-cause mortality. When compared to carbamazepine, levetiracetam was linked with a lower risk of cardiovascular death, but there was no meaningful difference in total mortality.

Reference:

Larsson D, Baftiu A, Johannessen Landmark C, et al. Association Between Antiseizure Drug Monotherapy and Mortality for Patients With Poststroke Epilepsy. JAMA Neurol. 2022;79(2):169–175. doi:10.1001/jamaneurol.2021.4584

Keywords: Stroke, epilepsy, antiseizure, lamotrigine, carbamazepine, valproic acid, cardiovascular, levetiracetam, survival, death, JAMA