Rescue therapies for seizure emergencies: current and future landscape

Abstract

Seizure emergencies—status epilepticus and seizure clusters—require rapid evaluation and treatment. Several consensus-based guidelines support a prompt use of intravenous benzodiazepines as the first-line therapy in seizure emergencies. However, most seizure emergencies start outside the hospital settings. Until recently, approved prehospital rescue therapies were limited to rectal diazepam and buccal midazolam (Europe only). The author provides a narrative review of rescue therapies for seizure emergencies based on a comprehensive literature review (PubMed and OvidSP vendors with appropriate keywords to incorporate recent evidence) to highlight the changing landscape of seizure recue therapies. A commercial version of intranasal midazolam was approved by the FDA in 2019 for 12\u2009≥\u2009years old with seizure clusters. In 2020, the FDA also approved a proprietary vitamin E solution–based diazepam nose spray to abort seizure clusters in\u2009≥\u20096 years old subjects. Other than these two new options, the author discussed two previously approved therapies: rectal diazepam and buccal midazolam. The review also includes the use of intramuscular diazepam and midazolam, clonazepam wafer, sublingual and intranasal lorazepam in seizure emergencies. Besides the availability of new therapies from successful trials in controlled settings, the real-world challenges of using rescue medicines in community settings are slowly emerging. With multiple options, a more robust and updated cost-effective analysis of different rescue medicines needs to be performed using effectiveness data from the literature and cost data from publicly available market prices. Further research is also ongoing to develop alternative non-intravenous treatment options for outpatient settings. Lastly, several other non-benzodiazepine drugs, such as allopregnanolone, propofol, and brivaracetam, are also currently under development for seizure emergencies.