Midazolam is a benzodiazepine that is given to children before a medical procedure to relieve anxiety. It also is used as the first-line treatment of status epilepticus in children. Status epilepticus is when seizures last longer than five minutes, or multiple seizures occur close together without the patient recovering between them.

Children with Dravet syndrome often experience status epilepticus, which can be life-threatening. Midazolam is a so-called rescue medicine that can be used to stop a seizure before it progresses to a medical emergency.

How midazolam works

Midazolam acts on the brain by binding to GABA-A receptors and enhancing the effect of the inhibitory cell-signaling molecule GABA. This causes brain cells to become less excitable, stopping the seizure.

Midazolam is highly lipid-soluble, which allows it to cross the blood-brain barrier, so therapeutic effects occur rapidly. However, the medicine has a short half-life and follow up treatment usually is required.

Midazolam in clinical trials

The effectiveness of midazolam has not been tested in controlled clinical trials in Dravet Syndrome specifically. However, it has been studied for status epilepticus and seizures in general.

A double-blind, randomized, Phase 3 clinical trial (NCT00809146) called RAMPART investigated the effectiveness of midazolam injected into the muscle (intramuscular) compared to Ativan (lorazepam) injected into the bloodstream for the treatment of status epilepticus. The study found that patients treated with intramuscular midazolam were more likely to have a cessation of symptoms before arrival at the hospital and that they were less likely to be hospitalized following the seizure.

A systematic review of data on the effectiveness of midazolam given by mouth or through the nose in epileptic seizures was published in 2012. The review analyzed more than 10 clinical studies, which in total enrolled 1,112 patients, ages one month to 72 years. The review concluded that midazolam given through the mouth or nose was safe and effective in controlling seizures.

An active Phase 3 open-label clinical trial (NCT03336450) is looking at whether oromucosal midazolam is safe and effective in children with status epilepticus in the community setting. Oromucosal administration is when the medicine is placed against the sides of the gums and cheek so that it is absorbed directly into the bloodstream. The primary goal of this trial is a cessation of seizures within 10 minutes of treatment that lasts for at least 30 minutes. The study is recruiting up to six participants in multiple locations in Japan.

Other information

The most common side effects of midazolam are sedation, euphoria, irritability, trouble breathing, and losing control of bodily functions. Follow-up doses are best applied at the hospital in case of respiratory depression, a condition characterized by slow and ineffective breathing.

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