Novel medications for neonatal seizures: Bumetanide and topiramate

Abstract

Novel medications to treat neonatal seizures have been the subject of numerous recent basic science research and clinical papers describing the potential and need for more effective and safe antiepileptic drugs (AEDs) for this unique population. This interest has been fueled in part by the notion that seizures, particularly when refractory, likely contribute to brain injury, later epilepsy and neurodevelopmental impairments. The population of newborns with seizures presents unique challenges, because of the often significant differences in the pharmacokinetics, safety and efficacy of medications when compared with older children and adults. Bumetanide and topiramate are two novel AEDs that have mechanisms of action uniquely suited to suppressing seizures in the newborn brain, with promising basic science data supporting their use in human newborns. Furthermore, these novel medications offer the potential of neuroprotective effects when used to treat refractory seizures caused by acute insults to the neonatal brain. The available data regarding the mechanism of action, pharmacokinetics, and safety of these two AEDs will be described, as well as the data needed to bring these two agents into routine use in the human newborn with seizures.

Keywords

Neonatal seizures - bumetanide - topiramate - hypoxic-ischemic encephalopathy - brain injury - pharmacokinetics - safety - neuroprotection - neurologic outcome