Clinicians currently have one non-intravenous choice to control occasional bursts of increased seizure activity—rectal diazepam. Two studies, however, hold promise of a more pleasant non-invasive option—a midazolam nasal spray (abstracts 3.269, 3.271). The two studies, which will be presented at the 2017 American Epilepsy Society (AES) annual meeting in Washington, DC, outline the safety and efficacy of the nasal spray.

Nasal spray. (Source: Pixabay)

The U.S. Food and Drug Administration has approved midazolam for anesthesia, preoperative sedation, anxiolysis and amnesia, but not yet for seizure disorders.

The double-blind ARTEMIS-1 trial evaluated the efficacy of midazolam in patients who experienced seizure clusters and were already receiving antiepileptic drugs. The researchers randomized 262 participants 2:1 to receive midazolam or placebo from their caregiver when a seizure cluster occurred.

During the study, 201 patients experienced a seizure cluster. Of those, 134 received midazolam and 67 received placebo. Patients receiving midazolam were 50% more likely to achieve treatment success, defined as seizure cessation within 10 minutes and no recurrence from 10 minutes to six hours after treatment. A majority of the midazolam group were successfully treated (54.7%) compared to 34.4% of the placebo group. Patients in the midazolam group were also less likely to experience recurrence of a seizure cluster within four hours of treatment (38.1%) compared to those in the placebo group (59.7%).

Treatment emergent adverse events occurred in half the participants in the test dose phase of ARTEMIS-1. During the outpatient comparative phase, 28% of those who received midazolam and 22% of those receiving placebo reported adverse events, most of which were mild-to-moderate in intensity. Only 4.8% of AEs during the test dose phase and 1% during the comparative phase were serious and just 1% of those were considered related to the midazolam. The most common adverse events were nasal discomfort, somnolence, increased lacrimation, abnormal product taste and throat irritation. There were no reported deaths during or after the study.