Abstract: Provided are compositions and methods for treating and/or preventing seizure-induced death in subjects in need thereof. In some embodiments, the methods include methods for inducing an audiogenic seizure and/or seizure-induced death, treating and/or preventing death associated with seizures in subjects, preventing sudden unexpected death in epilepsy (SUDEP) in subjects, preventing and/or reducing the risk of death in subjects having SCN8A gain-of-function mutations, preventing or reducing the risk of death associated with tonic seizures in subjects, and preventing or reducing the risk of death associated with epileptic seizures in subjects. Also provided are animals that have been modified to carry gain-of-function SCN8A mutations and methods for using the same to identify compounds that have activity in treating and/or preventing seizures and/or seizure-induced death in subjects.