A COMPARISON OF RECTAL DIAZEPAM GEL AND PLACEBO FOR ACUTE REPETITIVE SEIZURES

Background Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often requ ired. Rectal diazepam gel is a promising therapy. Methods We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were r andomly assigned to receive either rectal diazepam gel, at doses rangi ng from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetiti ve seizures and a second dose four hours later. Adults received three doses - one dose at onset, and two more doses 4 and 12 hours after ons et. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. Results Of 125 study patients (64 assigned to diazepam and 61 to place bo) with a history of acute repetitive seizures, 91 (47 children and 4 4 adults) were treated for an exacerbation of seizures during the stud y period. Diazepam treatment was superior to placebo with regard to th e outcome variables related to efficacy: reduced seizure frequency (P< 0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P<0.001 ). Post hoc analysis showed diazepam to be superior to placebo in redu cing seizure frequency in both children (P<0.001) and adults (P=0.02), but only in children was it superior with regard to improvement in gl obal outcome (P<0.001). The time to the first recurrence of seizures a fter initial treatment was longer for the patients receiving diazepam (P<0.001). Thirty-five patients reported at least one adverse effect o f treatment; somnolence was the most frequent. Respiratory depression was not reported. Conclusions Rectal diazepam gel, administered at hom e by trained care givers, is an effective and well-tolerated treatment for acute repetitive seizures. (N Engl J Med 1998;338:1869-75.) (C) 1 998, Massachusetts Medical Society.