AUTHOR=Yi Zhan-Miao , Zhong Xu-Li , Wang Ming-Lu , Zhang Yuan , Zhai Suo-Di 

TITLE=Efficacy, Safety, and Economics of Intravenous Levetiracetam for Status Epilepticus: A Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00751

DOI=10.3389/fphar.2020.00751

ISSN=1663-9812

ABSTRACT=Objective: To evaluate efficacy, safety and economics profiles of intravenous levetiracetam (LEV) for status epilepticus (SE).
Methods: We searched PubMed, Embase, the Cochrane Library, Clinicaltrials.gov and OpenGrey.eu for eligible studies published from inception to June 12th 2019. Meta-analyses were conducted to quantitatively synthesize included studies.
Results: A total of 478 studies were obtained. Five systematic reviews (SRs)/meta-analyses, 9 randomized controlled trials (RCTs), 1 non randomized trial and 27 case series/reports and 1 economic study met the inclusion criteria. The included SRs enrolled patients with convulsive SE, non-convulsive SE and refractory SE. Five SRs evaluated rates of seizure cessation, and indicated no statistically significant difference when LEV was compared with lorazepam (LOR), phenytoin (PHT) or valproate (VPA). Pooled results of included RCTs indicated no statistically significant difference in seizure cessation when LEV was compared with LOR (OR=1.04, 95% CI 0.37 to 2.92), PHT (OR=0.90, 95% CI 0.64 to 1.27), and VPA (OR=1.47, 95% CI 0.81 to 2.67); and no statistically significant difference in seizure freedom within 24 hours when LEV was compared with LOR (OR=1.83, 95% CI 0.57 to 5.90) and PHT (OR=1.08, 95% CI 0.63 to 1.87). Pooled results of included RCTs also showed that LEV did not increase the risk of mortality during hospitalization compared with LOR (OR=1.03, 95% CI 0.31 to 3.39), PHT (OR=0.89, 95% CI 0.37 to 2.10), VPA (OR=1.28, 95% CI 0.32 to 5.07), and placebo (plus clonazepam, OR=0.73, 95% CI 0.16 to 3.38). LEV had lower need for artificial ventilation (OR=0.23, 95% CI 0.06 to 0.92) and a lower risk of hypotension (OR=0.15, 95% CI 0.03 to 0.84) compared to LOR. A trend of lower risk of hypotention and higher risk of agitation was found when LEV was compared with PHT. Case series and case report studies indicated psychiatric and behavioral adverse events of LEV. Cost-effectiveness evaluations for benzodiazepines-resistant convulsive SE with decision analysis model indicated LEV as the most cost-effective non-benzodiazepines AED. 
Conclusions: LEV has a similar efficacy as LOR, PHT and VPA for SE, but a lower need for ventilator assistance and risk of hypotension.