Intermittent Use of Midazolam Favorable for Seizure Cluster Episodes

Most patients who experience seizure cluster episodes and are treated with intranasal midazolam experience return to full baseline functionality (RTFBF) within 24 hours of administration, according to study findings published in Epilepsy & Behavior. 

Rescue treatment for seizure clusters, or acute repetitive seizures, is underused. A prompt RTFBF is important in maintaining or improving the quality of life of patients with seizure disorders. In the United States, intranasal midazolam is approved to treat acute intermittent, stereotypic episodes of frequent seizure activity that are distinct from an individual’s usual seizure pattern in patients age 12 and older.

Researchers conducted a post hoc analysis to analyze RTFBF in seizure cluster episodes treated with midazolam among patients with repeated intermittent seizure clusters.

Data was analyzed from ARTEMIS-2 (ClinicalTrials.gov Identifier: NCT01529034), an open-label extension international trial conducted between August 2012 and April 2017. 

The study population included patients aged 12 and older diagnosed with epilepsy who had an adult caregiver able to recognize and administer treatment for seizure cluster. Some exclusion criteria were if a patient’s seizure cluster developed into status epilepticus, psychosis, major depressive episode, active suicidality, or pregnancy.

Each patient received a treatment kit with 2 5-mg doses of midazolam, which was enough to treat 1 seizure cluster episode, and was instructed to return to the trial center to receive additional kits. The researchers required an interval of at least 72 hours for midazolam-treated seizure cluster episodes. 

Caregivers administered 1 5-mg dose of midazolam when the participant experienced a seizure cluster and could administer an additional dose if the episode did not terminate within 10 minutes or if another seizure occurred within 10 minutes to 6 hours after administration of the initial dose.

A total of 161 patients (average age, 32.9) were administered midazolam for 1998 seizure cluster episodes. The average duration of a seizure cluster was 1.0 hour and the median number of seizures was 6.0 within a seizure cluster episode. 

Of these patients, 1201 (60.2%) required 1 dose and 795 (39.8%) required 2 doses. The RTFBF within 24 hours in patients treated with 1 dose was 97.2% and with 2 doses was 94.2%. 

Among patients who were treated with 2 doses of midazolam, the second dose was administered more than 6 hours after the initial dose in 3.4% of the seizure cluster episodes.

The RTFBF was similar in seizure cluster episodes treated with 1 or 2 doses of midazolam, with approximately 30% of patients reporting an RTFBF within 30 minutes and 50% within 1 hour. However, there was a slightly higher proportion of participants with RTFBF between 2 to 6 hours among patients receiving 1 dose compared to 2 doses.  

“Further investigation is needed to identify the factors that can contribute to RTFBF after MDZ-NS [midazolam nasal spray] use, which may include the number and type of seizures in the treated SCE [seizure cluster episodes], as well as the SCE’s duration, concomitant medications, comorbidities, age, and body weight,” the researchers concluded. “Additionally, further studies are needed to assess the impact of RTFBF on patients’ quality of life and treatment adherence in real-world use.”

Study limitations include a lack of a comparator group, a lack of information regarding seizure types, and reliance on caregiver assessment for RTFBF.