Felbamate: a double-blind controlled trial in patients undergoing presurgical evaluation of partial seizures. Felbamate for partial seizures: results of a controlled clinical trial. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). The Felbamate Study Group in Lennox-Gastaut Syndrome.
We studied the efficacy and safety of felbamate, an investigational antiepileptic drug, in a unique, double-blind, placebo-controlled trial. Sixty-four patients with refractory partial-onset seizures who completed a routine evaluation for epilepsy surgery met seizure frequency entry criteria. Each patient received felbamate or placebo in addition to the anticonvulsant regimen present at the conclusion of the presurgical evaluation. The treatment phase consisted of an 8-day inpatient period and a 21-day outpatient period. The efficacy variable was time to fourth seizure. The difference in time to fourth seizure was statistically significant (p = 0.028) in favor of felbamate. Eighty-eight percent of the patients in the placebo group had a fourth seizure during the treatment phase compared with 46% of the patients in the felbamate group (p = 0.001). Adverse experiences with felbamate were generally mild or moderate in severity. This trial demonstrated the ability of felbamate to quickly and safely reduce the occurrence of frequent partial-onset seizures and maintain effective seizure control following reductions in the dosages of standard antiepileptic drugs. Felbamate (2-phenyl-1,3-propanediol dicarbamate) has a favorable preclinical profile in animal models of epilepsy. We present the results of a double-blind, randomized, placebo-controlled clinical trial in patients with partial seizures. Criteria for entry included a requirement for four or more partial seizures per month despite concomitant therapeutic blood levels of phenytoin and carbamazepine. Fifty-six patients (mean age, 31.4 years; 32 men, 24 women) completed the trial. The mean seizure frequencies for the 8-week periods analyzed were felbamate = 34.9, placebo = 40.2. Felbamate was statistically superior to placebo in seizure reduction, percent seizure reduction, and truncated percent seizure reduction. The mean felbamate dosage was 2,300 mg/d. Plasma felbamate concentrations ranged from 18.4 to 51.9 mg/l, mean = 32.5 mg/l. Adverse experiences during felbamate therapy were minor and consisted primarily of nausea and CNS effects. This trial indicates that felbamate is safe and effective in the treatment of comedicated patients with severely refractory epilepsy. The Lennox-Gastaut syndrome is a childhood disorder characterized by multiple types of seizures, mental retardation, characteristic electroencephalographic abnormalities, and resistance to standard antiepileptic drugs. Felbamate is an investigational antiepileptic drug with a preclinical profile that suggests it would be effective in patients with multiple types of seizures. In controlled clinical trials, felbamate was superior to placebo in reducing the frequency of refractory partial-onset seizures.
                We studied the efficacy of felbamate in 73 patients ranging in age from 4 to 36 years who had the Lennox-Gastaut syndrome. During a 28-day base-line phase, the patients received their usual antiepileptic therapies. At the end of this phase, felbamate or placebo was administered for 70 days in addition to the current antiepileptic medications. The dosage of felbamate was titrated during the first 14 days of the treatment phase to a maximum of 45 mg per kilogram of body weight per day or 3600 mg per day, whichever was less. The primary efficacy variables were the total number of seizures counted during a four-hour period of video recording, parents' or guardians' global evaluations of the patients' quality of life, and the total number of atonic seizures, as reported by parents or guardians.
                The patients treated with felbamate had a 34 percent decrease in the frequency of atonic seizures, as compared with a 9 percent decrease in the patients who received placebo (P = 0.01). The felbamate-treated patients had a 19 percent decrease in the total frequency of seizures, as compared with a 4 percent increase in the placebo group (P = 0.002). The global-evaluation scores were significantly higher in the felbamate group than in the placebo group from day 49 to the end of the study. There were no significant differences in the frequency of seizures occurring during video monitoring, but there was a significant reduction (P = 0.017) in the number of tonic-clonic seizures during the maintenance period in the felbamate group. The types and frequency of side effects were similar in the two treatment groups.
                Felbamate is beneficial in patients with the Lennox-Gastaut syndrome.
In view of the methodological deficiencies, limited number of individual studies and differences in outcome measure, we have found no reliable evidence to support the use of felbamate as an add-on therapy in patients with refractory partial-onset epilepsy. A large scale, randomized controlled trial conducted over a greater period of time is required to inform clinical practice.