Personalizing Treatment May Improve Outcomes for Patients With Epilepsy

In one study, people with prolonged seizures were randomized to intramuscular midazolam or IV lorazepam for prehospital treatment. The percentage of patients arriving at the emergency room without seizures and without a need for rescue therapy was higher among patients receiving intramuscular midazolam than among those receiving IV lorezapam. The reason for the difference may be that it takes a longer time to prepare and inject a drug IV than to administer it intramuscularly, said Dr. Perucca.

Rectal administration has the advantage of enabling rapid absorption of certain drugs, most notably diazepam. Researchers observed that effective serum concentrations are achieved within three to five minutes of rectal administration of a suitable formulation of diazepam. In two pivotal studies of rectal diazepam for the prevention of recurrence of acute repetitive seizures, the drug approximately doubled the proportion of patients who remained without seizures over 12 hours, compared with placebo. Many other drugs could be formulated for rectal delivery, noted Dr. Perucca.

Buccal administration has gained popularity since the introduction of buccal midazolam, which is available in Europe for stopping prolonged convulsive seizures. In two studies, the percentage of children whose seizures ceased within 10 minutes without recurrence in one hour was larger among participants receiving buccal midazolam than among participants receiving rectal diazepam. In another trial, the time to clinical effect after decision to treat was shorter with buccal midazolam than with IV diazepam, likely because of the time it takes to prepare the syringe and inject the drug, said Dr. Perucca.

Intranasal drug delivery bypasses the blood–brain barrier and is easily applicable in convulsive, noncooperative patients. This route is only feasible, however, for potent drugs that do not require doses larger than 20 mg, said Dr. Perucca. It also raises concerns about intersubject variability. Nevertheless, one study found that time to effect after arrival to the emergency room was shorter with intranasal midazolam than with IV diazepam.

Several innovative techniques, such as imaging-guided drug delivery, eventually may expand neurologists’ options and enable AEDs to be delivered directly to the brain, said Dr. Perucca. Researchers also are developing responsive devices that can be implanted over the epileptic focus in the brain and deliver an AED automatically when they detect seizure activity. “Innovative ways of delivering drugs could lead to therapeutic breakthroughs in the future,” concluded Dr. Perucca.

—Erik Greb