Abstract
Background
Recent studies have shown conflicting results regarding the effectiveness of levetiracetam for treating benzodiazepine-refractory status epilepticus (SE) compared with phenytoin. Therefore, a meta-analysis was carried out to assess the value of levetiracetam versus phenytoin in the pharmacotherapy of benzodiazepine-refractory SE.
Objective
The aim of this systematic review and meta-analysis was to compare the efficacy and safety of levetiracetam and phenytoin in the treatment of benzodiazepine-refractory SE.
Methods
The MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) that had been conducted to evaluate levetiracetam versus phenytoin for benzodiazepine-refractory SE, to April 2020. The data were assessed using Review Manager 5.3 software. The risk ratio (RR) was analyzed using dichotomous outcomes, and calculated using a random-effect model.
Results
We pooled 1850 patients from 12 RCTs. Patients in the levetiracetam group had a significantly higher rate of clinical seizure cessation than in the phenytoin group (75.2% vs. 67.8%; RR 1.14, 95% confidence interval [CI] 1.05–1.25, p = 0.003). Moreover, less adverse events were observed in the levetiracetam group than in the phenytoin group (17.8% vs. 21.4%; RR 0.82, 95% CI 0.70–0.97, p = 0.02). In subgroup analysis, clinical seizure cessation was achieved more frequently with a higher dose of levetiracetam (> 30 mg/kg) [RR 1.15, 95% CI 1.00–1.32, p = 0.05]. Furthermore, in the subgroup of children, levetiracetam showed a higher rate of clinical seizure cessation than phenytoin (RR 1.13, 95% CI 1.02–1.25, p = 0.02).
Conclusion
Pharmacotherapy for BZD-refractory SE by LEV is superior to PHT in efficacy and safety outcomes.
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The authors acknowledge and thank Dr. Laxman Pujari for English proofreading.
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This work was supported by the Suzhou Health Talents Training Project (GSWS2019002).
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Tao Xue, Luxin Wei, Xiaotian Shen, Zilan Wang, Zhouqing Chen, and Zhong Wang declare they have no competing interests.
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ZW and ZC were the principal investigators. TX and LW designed the study and developed the analysis plan; analyzed the data and performed the meta-analysis; and contributed to the writing of the article. XS and ZW revised the manuscript and polished the language. All authors read and approved the final submitted paper.
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Xue, T., Wei, L., Shen, X. et al. Levetiracetam versus Phenytoin for the Pharmacotherapy of Benzodiazepine-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. CNS Drugs 34, 1205–1215 (2020). https://doi.org/10.1007/s40263-020-00770-0
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DOI: https://doi.org/10.1007/s40263-020-00770-0