Antiseizure Medications in Poststroke Seizures: A Systematic Review and Network Meta-Analysis

The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS.

We systematically searched electronic databases for studies on patients with PSS on ASMs. Our outcomes were seizure recurrence, adverse events, drug discontinuation rate, and mortality. We assessed the risk of bias using Cochrane Risk of Bias tool for randomized controlled trials and Risk Of Bias In Non-randomized Studies of Interventions tools. Using levetiracetam as the reference treatment, we conducted a frequentist network meta-analysis and determined the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation methodology.

Our search yielded 15 studies (3 randomized, 12 nonrandomized, N = 18,676 patients (121 early and 18,547 late seizures), 60% male, mean age 69 years) comparing 13 ASMs. Three studies had moderate and 12 had high risk of bias. Seizure recurrence was 24.8%. Compared with levetiracetam, very low-certainty evidence suggested that phenytoin was associated with higher seizure recurrences (odds ratio [OR] 7.3, 95% CI 3.7-14.5) and more adverse events (OR 5.2, 95% CI 1.2-22.9). Low-certainty evidence suggested that carbamazepine (OR 1.8, 95% CI 1.5-2.2) and phenytoin (OR 1.9, 95% CI 1.4-2.8) were associated with high drug discontinuation rates. Moderate to high-certainty evidence suggested that valproic acid (OR 4.7, 95% CI 3.6-6.3) and phenytoin (OR 8.3, 95% CI 5.7-11.9) were associated with higher mortality rates. Considering all treatments and using the GRADE approach for treatment ranking, very low-certainty evidence suggested that eslicarbazepine, lacosamide, and levetiracetam had the fewest seizure recurrences. Low to very low-certainty evidence suggested that lamotrigine had the fewest adverse events and drug discontinuations, whereas lamotrigine and levetiracetam exhibited low mortality rates with moderate-certainty evidence.

We found that levetiracetam and lamotrigine may be safe and tolerable ASMs for PSS. Despite ASM use, the seizure recurrence rate remains high in the PSS population. Owing to bias and confounding risks, these findings should be interpreted cautiously.

PROSPERO: CRD42022363844.