Midazolam nasal spray (MDZ-NS) is a new emerging rescue medication that suppresses epileptic seizures. Until now, few studies, pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and clinical trials have shown that midazolam nasal spray could become an effective and promising alternative to conventional routes (intravenous {IV}/rectal). Therefore, we thought of conducting a systematic review and meta-analysis of midazolam (MDZ) to assess its potential outcomes. The analysis was also evaluated based on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of midazolam nasal spray. A systematic literature search was carried out through various databases to identify studies of accounted outcomes of midazolam nasal spray (MDZ-NS). Randomized and other studies of patients (12 years or older) with seizure clusters (SCs) were included. A total of three full-text articles were considered for systematic review and meta-analysis as per the inclusion and exclusion criteria. The 5 mg MDZ-NS was observed to be equally safe as a placebo, and the risk ratio (RR) was 1.01 (95% confidence interval (CI): 0.67-1.53). After the administration of MDZ-NS, either the patients remained seizure-free for six hours or more or the seizure was terminated within 10 minutes and had no recurrence between 10 minutes and six hours. The risk ratio (RR) obtained was 1.54 (95% CI: 1.25-1.91). The result was statistically significant as a higher success rate was observed with the use of 5 mg midazolam nasal spray compared to placebo (p < 0.0001). Heterogeneity was not observed in the results of the included studies (inconsistency index {I2}: 0%). The present systematic review and meta-analysis demonstrated that 5 mg midazolam nasal spray was efficacious in treating patients with seizure clusters and is well-tolerated. Also, its use is relatively safe.

Although the treatment of epilepsy primarily focuses on prevention, recurrent seizures are unfortunately an ongoing reality, particularly in people with epilepsy who live with chronic refractory seizures. Rescue medications are agents which can be administered in urgent/emergent seizure episodes such as seizure clusters or prolonged seizures with the goal of terminating seizure activity, preventing morbidity, and decreasing the risk of further seizures.
This review first discusses clinical opportunities for rescue medications, with particular attention focused on seizure clusters and prolonged seizures, including their epidemiology, risk factors, and associated morbidity. Current rescue medications, their indications, efficacy, and adverse effects are discussed. We then discuss rescue medications and formulations which are currently under development, concentrating on practical aspects relevant for clinical care.
Rescue medications should be considered for all people with epilepsy with ongoing seizures. Recent rescue medications including intranasal formulations provide considerable advantages. New rescue medications are being developed which may expand opportunities for effective treatment. In the future, combining rescue medications with seizure detection and seizure prediction technologies should further expand opportunities for use and should reduce the morbidity of seizures and provide increased comfort, control, and quality of life for people living with epilepsy.