Benzodiazepine rescue medication administration for seizure clusters: Real-world retrospective outcomes

Benzodiazepine rescue medications are established as therapy for acute termination of seizure clusters. A post-hoc analysis of a clinical trial of seizure cluster treatment with diazepam nasal spray found a potential longer-term impact over a year of treatment. In this retrospective analysis, we tested the hypothesis that benzodiazepine-treated seizure clusters are associated with prolonged time to the next seizure cluster compared with untreated seizure clusters in a patient-reported real-world database.

We analyzed data on self-reported seizures and benzodiazepine rescue medication administration in the Seizure Tracker™ database between 2007 and 2022. Kaplan-Meier analysis was used to compare treated vs untreated seizure clusters with respect to time to start of the next seizure cluster or immediate-use medication administration. Mixed-effects analysis was used to compare the number of seizures per cluster for treated and untreated seizure clusters. Robustness of findings was evaluated across three operational seizure-cluster definitions: ≥2 seizures in 4 hours as primary analysis and in 6 and 24 hours as sensitivity analyses.

A total of 10 889 benzodiazepine immediate-use medication administrations (n = 220 patients) met inclusion criteria. Benzodiazepine rescue administrations were followed by longer time to the next seizure cluster or rescue administration, compared with untreated seizure clusters, corresponding to a median of 4.9 days following treated seizure clusters and a median of 0.8 days following untreated seizure clusters. This prolongation was driven by a minority of patients (accounting for 45.9% of seizure clusters in the sample) and patients were more likely to be women. The number of seizures per cluster was lower when treatment was administered earlier in the seizure cluster.

These retrospective real-world data suggest that the effect of benzodiazepines on termination of seizure clusters may be more pronounced when administration occurs earlier after onset, and support a hypothesis of a possible longer-term effect of benzodiazepines beyond immediate-use acute seizure termination.