Exploring proposed recommendations for immediate-use seizure medication: Treating both cluster and prolonged seizures with diazepam nasal spray.

Abstract

The Seizure Termination Project developed expert consensus recommendations for outpatient management of seizure clusters and prolonged seizures to prevent progression to a higher-level emergency. The consensus recommendations described therapeutic scenarios for seizure clusters (acute cluster treatment [ACT]) to prevent further seizures in a cluster and treatment to stop ongoing seizures that were expected to be prolonged (rapid and early seizure termination [REST]). Here, we review ACT and REST as categories and explore their practical application by examining patient-level data for diazepam nasal spray. ACT and REST criteria were examined using data from the long-term safety study that evaluated diazepam nasal spray for seizure clusters. To explore the effectiveness and duration of treatment for ACT, the proportion of seizure clusters for which second doses were administered within 24 h was used as a proxy. REST was investigated using the time from administration to seizure cluster termination; timing for the termination of prolonged seizures (5-15 min for the purposes of this analysis) in clusters also was examined. In the long-term safety study of diazepam nasal spray, a single dose demonstrated effectiveness at terminating a substantial majority of seizure clusters (3368/3853 [87.4%]) across 24 h, demonstrating its use as ACT. The majority of seizure clusters (2169/3225 [67.3%]) were recognized and treated quickly, within 5 min from onset, demonstrating its utility as REST. Notably, effectiveness was maintained in seizures treated after they had become prolonged. These findings from the large dataset of the long-term safety study of diazepam nasal spray demonstrate that it is of benefit in immediate use for both termination of an acute seizure and prolonged seizures within seizure clusters, thus supporting the recent expert consensus recommendations. Early use of a single rescue treatment can meet the need for ACT and REST, simplifying patient care. PLAIN LANGUAGE SUMMARY: An expert group defined 2 groups of seizure medicines for patients and caregivers to use. "ACT" medicines are for acute cluster treatment to prevent more seizures in a cluster. "REST" medicines for rapid and early seizure treatment stop prolonged seizures. Diazepam nasal spray for seizure clusters was looked at to see if it could fit in both categories. Study data showed that for most seizure clusters only 1 dose of diazepam nasal spray was used over 24 h (fitting ACT), and seizures were treated and ended quickly (fitting REST). One medicine for REST and ACT may make treatment simpler.