The New England Journal of MedicineRandomized Trial of Three Anticonvulsant Medications for Status Epilepticus

Navigating Efficacy and Safety: A Comparative Analysis of Anticonvulsants for Benzodiazepine-Refractory Status Epilepticus

In this in-depth randomized trial published in 2019, researchers scrutinized the effectiveness and safety profiles of three anticonvulsant medications—levetiracetam, fosphenytoin, and valproate—in treating patients with convulsive status epilepticus (SE) that remains unresponsive to benzodiazepines. This study provides critical insights for clinicians in selecting appropriate therapeutic interventions for this challenging and urgent medical condition, highlighting the comparative efficacy and safety outcomes associated with these medications.

Key Points:

• The trial focused on evaluating levetiracetam, fosphenytoin, and valproate in children and adults with convulsive SE resistant to benzodiazepines.
• Patients were assessed for the cessation of seizures and improvement in consciousness within 60 minutes post-drug infusion, without the need for additional anticonvulsant medication.
• A total of 384 patients participated, with levetiracetam (145 patients), fosphenytoin (118), and valproate (121) being the drugs under comparison.
• The trial was concluded early based on a prespecified futility rule, which indicated no significant superiority or inferiority among the drugs.
• Around 10% of the study cohort was found to have psychogenic seizures instead of true status epilepticus.
• Efficacy rates were close: levetiracetam showed a 47% success rate, fosphenytoin 45%, and valproate 46% in achieving the primary outcome.
• The safety profile was similar across the three medications, with no significant differences in severe adverse events like hypotension, intubation, seizure recurrence, or death.
• Notably, the fosphenytoin group experienced a higher, though not statistically significant, rate of hypotension and intubation, and more deaths were observed in the levetiracetam group.

From the Mayo Clinic:
SE is uncommon overall but is one of the most common brain-related medical emergencies. Experts estimate there are between 7 and 40 cases per 100,000 people each year. That means there are between 23,000 and 131,800 cases annually in the US. About 2% of seizures turn into SE and around 23% of new seizure cases involve status epilepticus.

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