Rapid and Sustained Seizure Termination With Midazolam in Open-Label Extension Study

Post hoc analysis of an open-label extension study (NCT01529034) showed treatment with midazolam nasal spray (Nayzilam; UCB Pharma, Smyrna, GA) terminated 92% of seizure cluster episodes. There was no seizure recurrence from 10 minutes of treatment to 24 hours for 85% of treated seizure cluster episodes. Of 1,996 seizure cluster episodes in 161 participants, 60.1% were treated with 1 dose of midazolam nasal spray and 39.9% were treated with 2 doses. 

The median time of administration of midazolam was 3 minutes with 18.5% treated immediately, 35.9% within 1 to 3 minutes, 28.3% within 4 to 10 minutes, and 17.3% treated after more than 10 minutes. 

The amount of time that passed between recognition of the seizure event and treatment did not affect the proportion of events terminated with 10 minutes of administering a first or second dose. Sustained seizure control, however, was more likely if midazolam nasal spray was administered sooner after a seizure began.

This was the first clinical trial to assess the effects of time from seizure onset to treatment with a nasal spray rescue medication. The effect of time to treatment on seizure recurrence emphasizes the importance of early, effective treatment and the need for education on use of rescue medications.

Participants in the study were administered a dose of midazolam nasal spray by caregivers when they experienced a seizure cluster episode. If seizures did not terminate within 10 minutes or recurred within 10 minutes to 6 hours, a second dose could be administered. Caregivers recorded the time from seizure onset to administration of midazolam nasal spray, time to seizure termination, and time to seizure recurrence. Of 1,998 cluster seizure episodes, 2 were excluded from this post-hoc analysis because the time from onset to first dose was not recorded. For episodes treated with 2 doses, seizure termination and recurrence were measured after the second dose.