Levetiracetam Versus Phenytoin for Seizure Prophylaxis Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Yong Yang, Fangshuo Zheng, Xin Xu, Xuefeng Wang

Seizure following traumatic brain injury (TBI) constitutes a common complication that requires effective prevention to improve the outcome of TBI. Phenytoin has been the only recommended antiepileptic drug (AED) for seizure prophylaxis; however, several shortcomings have affected its use. Intravenous levetiracetam has been available since 2006 and has been increasingly accepted as a seizure prophylaxis for brain injury, mainly due to its favorable pharmacokinetic features and minimal adverse events profile. However, the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI are not well clarified. The aim of this study was to assess the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI. We conducted a search of the MEDLINE, EMBASE, and Cochrane library databases to March 2016, and screened original research that included patients with TBI who received levetiracetam. We included randomized controlled trials (RCTs) or controlled observational cohort studies that compared levetiracetam and phenytoin, as well as uncontrolled case series regarding prophylactic levetiracetam following TBI. The outcomes included early or late seizure prophylaxis and safety. The estimates of seizure prophylaxis were pooled using a meta-analysis, and the estimates for the case series were pooled using descriptive statistics. A total of 1614 patients from 11 studies were included in this review, of whom 1285 patients from eight controlled studies (one RCT and seven cohort studies) were included in the meta-analysis. Levetiracetam was not superior to phenytoin with regard to early seizure prophylaxis (risk ratio [RR] 1.10, 95 % confidence interval [CI] 0.64-1.88); the estimate of early seizure incidence was 0.05 (95 % CI 0.02-0.08). Three studies that assessed late seizure did not indicate the superiority of levetiracetam to phenytoin. There were no differences in mortality during hospitalization or after 6 months, or in the number of patients with adverse reactions between levetiracetam and phenytoin. Levetiracetam does not appear to be superior to phenytoin in efficacy or safety with regard to early or late seizure prophylaxis following TBI; however, no class I evidence was identified. Additional evidence from high-quality studies is required.