Three most common anti-seizure drugs are all equally effective
Researchers from Michigan Medicine (MI, USA) have investigated the comparative effectiveness of the three most commonly prescribed anti-seizure drugs for the treatment of severe epilepsy. The results suggest that the three medications are equally effective and safe.
Researchers from Michigan Medicine (MI, USA) have investigated the comparative effectiveness of the three most commonly prescribed anti-seizure drugs for the treatment of refractory status epilepticus – a severe form of epilepsy. The results of the novel trial suggest that the three medications – levetiracetam, fosphenytoin and valproate – are all equally clinically effective and have similar risks of adverse events associated with them.
Status epilepticus is characterized by frequent seizures that collectively result in individuals loss of consciousness for more than 5 minutes; if untreated, severe brain damage or death can occur.
First-line treatment for status epilepticus involves the administration of benzodiazepines – central nervous system sedatives. Benzodiazepines are effective in two-thirds of patients experiencing status epilepticus; however, refractory status epilepticus can occur in patients for whom benzodiazepines are clinically ineffective.
Robert Silbergleit, senior study author and Professor of emergency medicine at Michigan Medicine, explained: “Optimizing emergency treatment with benzodiazepines has previously proven to reduce intensive care unit stays, hospitalization and other complications, but we have not had clinical trial data to tell us what works in those patients who continue to seize despite benzodiazepines.”
Silbergleit continued: “Although levetiracetam, fosphenytoin and valproate are three of the most commonly used intravenous drugs to treat refractory status epilepticus in both children and adults, before this study, we didn't know if one of these drugs worked better, or if any of them worked well at all.”
In this novel study, researchers carried out a response adaptive randomization clinical trial, entitled the Established Status Epilepticus Treatment Trial (ESETT). 384 pediatric and adult patients, who presented at emergency departments with refractory status epilepticus, were randomized to receive either levetiracetam, fosphenytoin or valproate treatment.
The primary study outcomes were improvements in patients’ responsiveness and halting of continued seizures within 1 hour of drug administration.
Investigators observed that patients who received levetiracetam, fosphenytoin or valproate met the primary study outcomes in 47%, 45% and 46% of instances respectively; this between-group variation, as well as the proportions of patients who received each of three drugs and experienced adverse events, was determined not to be statistically significant.
Contributing study author Jaideep Kapur (University of Virginia; VA, USA) concluded: “Using an innovative design for this clinical trial, we were able to answer this important question in a timely and cost-effective manner. In addition, this design lowered risk by reducing the chances that participants could have received what might have been determined to be the least effective treatment.”
Kapur J, Elm J, Chamberlain JM et al. Randomized trial of three anticonvulsant medications for status epilepticus. N Engl J Med. 381;2103–2113; (2019);