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Status Epilepticus – Three Anticonvulsants Head-to-Head – ESETT RCT

January 17, 2020

Written by Sam Parnell

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For status epilepticus refractory to benzodiazepines, the anticonvulsant medications levetiracetam, fosphenytoin, and valproate had similar rates of seizure cessation (all roughly half of patients), with similar incidence of serious adverse events.

Why does this matter?
The initial management of status epilepticus focuses on securing the ABCs (airway, breathing, circulation) and prompt administration of benzodiazepines. Early seizure cessation is crucial to reduce the morbidity and mortality associated with status epilepticus. However, up to a third of patients with seizures do not respond to benzodiazepine therapy, and further anticonvulsant medication is needed. Unfortunately, there is limited evidence comparing the efficacy and safety of commonly used anticonvulsant medications for status epilepticus.

Is there an optimal anticonvulsant for status epilepticus?
This was a prospective, randomized, multicenter, double-blind trial of 384 patients with benzodiazepine-refractory convulsive status epilepticus comparing the safety and efficacy of levetiracetam (60 mg/kg over 10 minutes, max dose 4500 mg), fosphenytoin (20 mgPE/kg over 10 minutes, max dose 1500 mgPE), and valproate (40 mg/kg over 10 minutes, max dose 3000 mg).

The primary outcome of cessation of status epilepticus and improvement in level of consciousness at 60 minutes occurred in roughly half of all patients (47% in levetiracetam group, 45% in the fosphenytoin group, and 46% in the valproate group) and results did not differ significantly between the three groups. The study was stopped early due to an interim analysis that found futility in continuing. In addition, there was no statistically significant difference in the incidence of adverse events. There was a trend toward more hypotension, respiratory depression, and intubation in the fosphenytoin group as well as more deaths in the levetiracetam group, but these differences weren’t significant.

It should be noted that approximately 10% of patients in this study had psychogenic nonepileptic seizures, unblinding occurred in a significant number of cases, and clinical criteria instead of EEG were used to determine the primary outcome. However, this study suggests that fosphenytoin, valproate, and levetiracetam have similar efficacy and are all valid options for treatment of benzodiazepine-refractory status epilepticus.


Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795.

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