The Impact of Levetiracetam versus Phenytoin as Second-Line Therapy for Status Epilepticus in the Emergency Department: A Systematic Review

Background: After benzodiazepine failure, status epilepticus (SE), a neurological emergency, necessitates immediate second-line treatment. Levetiracetam and phenytoin are commonly used, However, there is ongoing discussion over their relative safety and effectiveness in the emergency department (ED). Objective: to thoroughly examine the safety and efficacy of intravenous levetiracetam against phenytoin as a second-line treatment for SE in the ED that is benzodiazepine-refractory. Methods: The PRISMA 2020 standards were followed in conducting a systematic review. We looked for papers (within the previous five years) comparing the two medicines in ED patients with SE in PubMed/MEDLINE, Scopus, and Web of Science. Efficacy outcomes were seizure cessation rate, time to cessation, and 24-hour recurrence. Safety outcomes included adverse events. The Cochrane RoB 2 and ROBINS-I tools were used to evaluate the risk of bias. Results: Five studies (three RCTs, one quasi-experimental, one retrospective cohort; total n=523), all in pediatric populations, were included. Results indicated comparable efficacy for initial seizure cessation, with rates ranging from 78.8% to 94% for levetiracetam and 74.3% to 90.5% for phenytoin. According to two trials, levetiracetam considerably shortened the time it took for seizures to stop. Recurrence rates within 24 hours showed no significant difference. Safety data were insufficiently reported, but qualitative findings favored levetiracetam's tolerability. considerable variability, open-label designs, and a considerable risk of bias in non-randomized trials reduced the overall strength of the evidence. Conclusion: Levetiracetam and phenytoin demonstrate similar efficacy for aborting benzodiazepine-refractory SE in the ED. The choice between them may be guided by levetiracetam's potential for faster administration, more favorable pharmacokinetics, and superior safety profile, consistent with findings from larger pragmatic trials. Higher-quality, standardized research is needed to strengthen these conclusions.