Comparative efficacy and safety of second-line medications for status epilepticus: A network meta-analysis

Background: To systematically review the efficacy and safety of second-line medications for status epilepticus (SE).

Methods: Electronic searches were conducted in PubMed, Embase, and The Cochrane Library for randomized controlled trials of second-line medications for SE from inception to January 2024. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Network meta-analysis was performed using R 4.2.2 software.

Results: A total of 23 randomized controlled trials were analyzed, examining the efficacy of 5 different treatment regimens: levetiracetam (LEV), phenytoin (PHT), fosphenytoin (FPHT), valproate (VPA), and phenobarbital (PHB). The results of the network meta-analysis indicated that the seizure control rate ranking was as follows: PHB (98.1%) > LEV (60.7%) > FPHT (40.3%) > PHT (33.0%) > VPA (17.8%). The surface under the cumulative ranking (SUCRA) values revealed that PHB had the highest ranking (SUCRA, 91.8%), followed by VPA (SUCRA, 69.3%), PHT (SUCRA, 56.1%), and FPHT (SUCRA, 5.9%) for the recurrence of seizures within 24 hours. Subgroup analysis revealed that PHB was most effective for seizure control in both pediatric and adult populations, VPA demonstrated superior efficacy in children across various indicators, LEV was deemed the safest option for children and elderly individuals, and VPA was identified as the safest choice for adult patients.

Conclusions: PHB continues to be a prominent option for managing SE, although its safety profile warrants careful consideration. Meanwhile, both VPA and LEV offer distinctive advantages in the treatment of SE, with each demonstrating commendable safety profiles.