Randomized controlled trials of antiepileptic drugs for the treatment of post-stroke seizures: A systematic review with network meta-analysis

Objective: To determine the best available evidence on the efficacy and tolerability of antiepileptic drugs (AEDs) used to treat poststroke seizures and epilepsy. Methods: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and Opengrey.eu were searched for RCTs of AEDs used to treat post-stroke epilepsy. The following outcomes were considered: seizure freedom; occurrence of adverse effects (AEs); withdrawal for AEs. The methodological quality was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Adjusted indirect comparisons were made between each AED using controlled-release carbamazepine (CR-CBZ) as common comparator. Results: Only 2 RCTs were included, one comparing levetiracetam (LEV) with CR-CBZ and the other comparing lamotrigine (LTG) with CR-CBZ. No significant difference was found in seizure freedom between either LEV or LTG and CR-CBZ. Occurrence of AEs were lower for LEV and LTG than for CR-CBZ. Indirect comparisons showed no difference between LEV and LTG for seizure freedom (OR 0.86; 95%CI: 0.15-4.89). Occurrence of AEs was higher for LEV than for LTG (OR 6.87; 95%CI: 1.15-41.1). For withdrawal rates due to AEs, we found a large width and asymmetrical distribution of confidence intervals around the obtained OR of 10.8 (95% CI: 0.78-149.71). Conclusions: Direct and indirect comparisons did not find a difference in seizure freedom between the various AEDs, probably because of the small number of patients included. LEV and LTG appears better tolerated than CR-CBZ and LEV seems associated with more AEs than LTG. Further studies are required to provide robust evidence on efficacy and tolerability of AEDs for treating poststroke epilepsy.