Although rectal diazepam has been used on an outpatient basis in Europe for the treatment of severe, repetitive seizures for more than 20 years, such a formulation has only recently been labeled by the U.S. Food and Drug Administration for this purpose. Diazepam rectal gel is indicated for use in intermittent epilepsy to control bouts of increased seizure activity. Doses of diazepam rectal gel are individually packaged in pre-measured applicators for rectal insertion, ideal for use by care-givers in institutions or home settings. Cereghino and colleagues performed a multi-center, randomized, parallel, double-blind study to determine the safety and efficacy of the diazepam rectal formulation in patients with acute repetitive seizures.
In this study, caregivers were shown how to administer and monitor the medication by use of a video and illustrated written materials. Caregivers received close support and follow-up and had access to medical advice at all times. Response to the medication was measured by time until next seizure and seizure count, and through a global assessment completed by the caregivers and study investigators.
For study purposes, the epileptic seizure type included primary-generalized, complex-partial and simple-partial seizures with a motor component. These seizure types are believed to be the ones recognized more accurately by caregivers. Acute repetitive seizures were distinct from unpredictable seizures or those provoked by a specific cause in that they had a predictable pattern such as an aura or prodrome that distinguished them from other seizures in type, frequency, severity or duration. Most of the 114 patients included in the study were taking other seizure medications as well.
Analysis of seizure count showed that the median number of seizures in patients receiving diazepam was zero, whereas patients receiving placebo had a median of two seizures. In the 12-hour observation period following the administration of diazepam, 55 percent of patients were seizure free compared with 34 percent of those given placebo. The overall assessment by caregivers was also significantly higher in the diazepam group. Although no statistically significant difference in adverse events was found, there was an increased rate of somnolence in the patients receiving diazepam. No episodes of respiratory depression or withdrawal from the study because of adverse events occurred.
The authors conclude that it is possible for well-informed caregivers to predict and prevent acute repetitive seizures at home. The convenience and ease of use of diazepam gel treatment offers families more flexibility and control and may prevent costly emergency room visits and hospital stays.