Andrew N. Wilner, MD

Disclosures

January 11, 2013

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Welcome. I am Dr. Andrew Wilner, reporting for Medscape from the American Epilepsy Society 66th Annual Meeting in San Diego, California. I would like to give you a brief introduction to some of the posters presented yesterday regarding new treatments for epilepsy that are both approved by the US Food and Drug Administration (FDA) and in development.

There has been a lot of research activity recently in the use of new formulations of benzodiazepines for the treatment of acute repetitive seizures and status epilepticus. Key goals in this research are to provide more rapid and convenient drug delivery. A study[1] published earlier this year in the New England Journal of Medicine demonstrated that intramuscular midazolam administered by autoinjector was at least as effective as intravenous lorazepam for the initial treatment of status epilepticus by emergency medical responders in the field.

Yesterday, I spoke with my old friend, Dr. Bassel Abou-Khalil, who is the lead investigator in a randomized, double-blind, placebo-controlled study of treatment for acute repetitive seizures with diazepam, also administered by autoinjector.[2] The study included 163 patients in 68 centers. Patients received 5, 10, 15, or 20 mg diazepam, depending upon their age and weight, which was administered by their caregiver or placebo. The primary endpoint was the time to a subsequent seizure in the next 12 hours. In the placebo group, 55% of patients had a subsequent seizure in the next 12 hours vs 35% of patients in the diazepam group, which was statistically significant in favor of diazepam. Injection site pain occurred in 17% and bleeding in 5% of the treatment group. No subjects had significant respiratory depression.

There were several posters regarding a new formulation of intranasal midazolam, currently known as USL261, which is also intended for use as outpatient rescue therapy. A safety study[3] explored 3 doses (2.5 mg, 5 mg, and 7.5 mg) in 90 subjects with epilepsy (60 adults with a mean age of 39 years and 30 adolescents with a mean age of 15 years). Maximal sedation occurred at 30 minutes and resolved by 4 hours. Sedation was higher with the higher doses of 5 mg and 7.5 mg compared with 2.5 mg. Psychomotor performance decreased with a maximal effect at 20 minutes and resolved by 3 hours.

Adverse effects were a little different from what we are used to because of the unique route of administration. The most common complaints were dysgeusia, oral pharyngeal pain, and rhinalgia. No significant respiratory depression or oxygen desaturation below 90% occurred. Three patients had increased blood pressure, 1 had decreased blood pressure, and 1 had increased heart rate.

Currently, the only FDA-approved treatment for acute repetitive seizures is diazepam rectal gel. Current research suggests that there may be new intramuscular or intranasal options for outpatient rescue therapy. I would be remiss if I didn't mention that there is a new [antiseizure] drug, perampanel, that has recently been FDA-approved as adjunctive therapy for partial seizures and should be available in 2013. Perampanel, which has a brand name of Fycompa®, is a noncompetitive AMPA glutamate receptor antagonist that represents a novel mechanism for [antiseizure] drugs. Consequently, perampanel is a welcome option for those who believe that rational polytherapy is the logical approach for the treatment of people with refractory epilepsy. Where exactly perampanel fits in the treatment algorithm will become more clear as experience is gained with this new drug.

I think that is all we have time for today. With the FDA approval of perampanel, we now have another drug with a new mechanism of action for patients with partial-onset seizures. In addition, late-stage research promises one if not more new treatment options for acute repetitive seizures and status epilepticus. I am Dr. Andrew Wilner. Thank you for joining me for this brief review of highlights of new therapies from the American Epilepsy Society meeting in San Diego, California.

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