There are three treatment options commonly used by physicians in the emergency room to treat patients with refractory status epilepticus, severe seizures that persist after benzodiazepine medications, which can be effective in controlling seizures in more than two-thirds of patients. New findings released in the New England Journal of Medicine show the 3 medications, levetiracetam, fosphenytoin, and valproate, are both safe and effective in treating patients with this illness. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
“Physicians can be assured that the specific treatment they choose for their patients with status epilepticus is safe and effective and may help them avoid the necessity to intubate the patient as well as remains in the intensive care unit,” said Robin Conwit, M.D., NINDS program director and an author of the study. “This was a really collaborative, multidisciplinary research that involved pediatricians, emergency medicine doctors, neurologists, pharmacologists, and biostatisticians all contributing their expertise.
“From the Established Status Epilepticus Treatment Trial (ESETT), headed by Robert Silbergleit, M.D., professor at the University of Michigan, Ann Arbor; Jordan Elm, Ph.D., professor in Medical University of South Carolina; James Chamberlain, M.D., professor at George Washington University; and Jaideep Kapur, M.B., B.S., Ph.D., professor at the University of Virginia, over 380 kids and adults were randomized to receive levetiracetam, fosphenytoin, or valproate when they arrived to the emergency area having a seizure.
The researchers were trying to determine which of the anticonvulsant medication was most effective in stopping seizures and enhancing a patient’s degree of responsiveness within 60 minutes of administering treatment.The results showed that the three medications ceased seizures and improved responsiveness in roughly half of the study participants. Specifically, these benefits were seen in 47% of subjects in the levetiracetam class, in 45% of participants in the fosphenytoin category and at 46% of subjects in the valproate group.
These differences weren’t statistically significant.There were no differences in severe side effects one of the medication.”Our analysis suggests that clinical outcomes are driven by factors other than drugs. Differences in how doctors decide to treat status epilepticus, like when they give more drugs or when compared to anesthetize patients and set them to a mechanical ventilator, may be more significant than the particular treatments used to control seizures in patients,” explained Dr. Silbergleit.The study was discontinued when a planned interim analysis revealed that the medications were equally safe and effective.ESETT researchers utilized a clinical trial design called response adaptive randomization to improve the study’s efficiency and optimize the chances of identifying the best treatment.
The study used an algorithm to determine which drugs patients could get based on collecting trial data.”Using an innovative design for this clinical trial, we were able to answer this important question in a timely and cost-effective fashion,” said Dr. Kapur. “In addition, this design lowered risk by lowering the chances that participants could have obtained what could have been ascertained to be the best treatment.”Status epilepticus is characterized by person seizures or a number of seizures close together lasting over five minutes, using a reduction of consciousness.
If not treated, it can lead to severe brain damage or death. Benzodiazepines are the first line of therapy for status epilepticus and are effective in two-thirds of patients. Refractory status epilepticus occurs in those patients in whom benzodiazepines don’t stop their seizures.Further research is needed to stop disease status epilepticus and also to find treatment options to the patients whose seizures don’t respond to the three drugs researched in this study.