What is the role of midazolam in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Midazolam intranasal is a very short-acting, water-soluble imidazobenzodiazepine. Solubility of midazolam is accomplished by the presence of an imidazole ring fused at positions 1 and 2 of the benzodiazepine nucleus, which replaces the ketone at position 2 of the nucleus. The imidazole ring allows midazolam to readily form salts, which have increased aqueous solubility and stability compared with other benzodiazepines. The exact mechanism of action for midazolam is not fully understood, but it is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABA-A receptor. Midazolam is primarily metabolized by the liver and intestinal CYP3A4 to its pharmacologic active metabolite, 1-hydroxy midazolam (also termed alpha-hydroxymidazolam), which is at least as potent as the parent compound. Midazolam intranasal is indicated for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in adults and children aged 12 years or older with epilepsy.

Approval was based on the ARTEMIS-1 clinical trial (n=262), Patients randomized to treatment, 201 treated a seizure cluster with double-blind study drug (n=134 midazolam intranasal; n=67 placebo) and were included in the modified intent-to-treat population. [40] The proportion of subjects with treatment success was significantly greater in those treated with midazolam intranasal (53.7%) compared with placebo (34.4%; P=.0109). The proportion of subjects with recurrence of seizure(s) from 10 minutes to 4 hours after study drug administration was significantly lower with midazolam intranasal (38.1%) compared with placebo (59.7%; P=.0043).

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