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Levetiracetam versus Phenytoin for the Pharmacotherapy of Benzodiazepine-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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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, = 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, = 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, = 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, = 0.02).

Conclusion

Pharmacotherapy for BZD-refractory SE by LEV is superior to PHT in efficacy and safety outcomes.

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Acknowledgements

The authors acknowledge and thank Dr. Laxman Pujari for English proofreading.

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Correspondence to Zhouqing Chen or Zhong Wang.

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Funding

This work was supported by the Suzhou Health Talents Training Project (GSWS2019002).

Conflicts of interest

Tao Xue, Luxin Wei, Xiaotian Shen, Zilan Wang, Zhouqing Chen, and Zhong Wang declare they have no competing interests.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Author contributions

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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