Midazolam Nasal Spray May Reduce Seizures

A nasal spray formulation of midazolam may diminish repeated seizures and lower the risk of generalized tonic-clonic seizures in hospitalized epilepsy patients, researchers found.

In a retrospective analysis of data from a German university epilepsy center, those given intranasal midazolam during or right after a seizure remained free of seizures longer than those not given the drug (5.83 hours versus 2.37 hours), according to Lara Kay, a doctoral candidate at Philipps University in Marburg in Germany, and colleagues.

Those who didn’t get the drug also had a higher risk of generalized tonic-clonic seizures over the next 24 hours (odds ratio 4.67, 95% CI 1.06 to 2.12), they reported online in Epilepsia.

The researchers noted that it’s important to give anticonvulsants quickly, easily, and safely when managing repetitive and prolonged seizures, both in the hospital and in the community setting.

The gold standard treatment in such cases is intravenous lorazepam, but getting venous access may be a challenge during a seizure, and it may not be possible for a caregiver to do so outside of a hospital in an emergency situation.

Other formulations for home use have included rectal diazepam, which hasn’t had good uptake for a number of reasons, including stigma and shame, the researchers said. There’s also buccal midazolam, which has been approved in Europe.

Intranasal midazolam is an emerging technique for periprocedural sedation and for acute seizure control. The idea is to have a formulation that allows for rapid and easy administration. It’s been studied in home use, with no differences in efficacy or complications when compared with intravenous diazepam.

Kay and colleagues reviewed the records of 75 patients, mean age 35, who were treated with intranasal midazolam at their center, during or right after an epileptic seizure from 2008 to 2014.

The nasal spray was manufactured by the hospital’s pharmacy, and it delivered a dose of 2.5 mg midazolam per puff. The average dose per patient was 5 mg, or two sprays. It took a median time of 2.17 minutes to give intranasal midazolam.

They found that over the next 12 hours, the number of seizures was significantly lower for those who took intranasal midazolam. The median seizure-free interval was significantly longer for those who had the nasal spray than for those who didn’t (P=0.015).

They noted that the likelihood of a patient developing a subsequent seizure was four higher in first hour and fell gradually after 12 hours (OR 4.33, 95% CI 1.30-14.47 and OR 1.5, 95% CI 1.06-2.12, respectively).

Only four patients (5.3%) had an adverse event. Three patients had nasal irritation, while in the fourth, administration was delayed by the patient’s ictal automatisms and head turning.

There were no serious adverse events and the treatment was generally well-tolerated, the researchers said.

“This study provides evidence that ictal and immediate postictal administration of intranasal midazolam is a well-tolerated procedure and prevents subsequent seizures for a 12-hour period and especially generalized tonic-clonic seizures for a 24-hour period,” they concluded.

They added that intranasal midazolam is “easy to employ, and it can be delivered from any position. Even during a seizure, it takes little time to administer the dose, and patients do not need to be restrained.”

Another challenge is that there’s no commercial preparation available, but it still may be an inexpensive way to reduce the costs of morbidity and mortality associated with seizure activity, they concluded.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco