Felbamate Monotherapy: Implications for Antiepileptic Drug Development

Abstract

We studied the effect of felbamate (FBM) monotherapy on seizure rate in patients with partial and secondarily generalized seizures undergoing presurgical monitoring at a single site. The study design was a double-blind placebo-controlled parallel monotherapy trial. Forty patients whose seizures had not been controlled by standard antiepileptic drugs (AEDs) were randomized. Seizure type was confirmed by video-EEG monitoring. All baseline AEDs were discontinued, and patients were drug-free for 5.3 +/- 2.4 days before randomization to FBM or placebo. After a 4-day titration, seizures were counted for 14 days. Patients receiving FBM had significantly lower seizure rates, whether all randomized patients, patients who survived titration, or study completers were compared. Eight of 19 placebo patients randomized to placebo, as compared with 13 of 21 receiving FBM, completed the 18-day study. Two FBM patients dropped out due to seizures, and 6 dropped out due to side effects, including anxiety, difficulty sleeping, abdominal discomfort, acute psychosis, and orobuccal dyskinesias. Ten placebo patients met the criteria for premature discontinuation owing to seizures, and 1 hd an episode of panic. There was no evidence of hepatic or hematologic toxicity. FBM reduces seizure frequency in patients with localization-related epilepsy.

A Workshop on Antiepileptic Drug Monotherapy Indications

“…6 (70). Two FBM patients dropped out because of meeting seizure exit criteria, and six, because of side effects, whereas in the placebo group, 10 patients dropped out because of meeting seizure exit criteria, and one, for side effects (Fig.…”

“…Proportion of felbamate (FBM) versus placebo (PBO) patients remaining in the NIH presurgical monotherapy trial(70).…”

Epilepsy: Mechanisms of Drug Action and Clinical Treatment

“…One strategy to achieve approval for ''monotherapy'' involves inpatient drug withdrawal (standard during video-EEG monitoring to identify seizure foci in patients being considered for surgery) followed by addition of experimental drug or placebo [123]. This process is expensive, may have relatively higher risks of increased seizures, and does not necessarily mirror conventional clinical treatment due to the effects of baseline AED withdrawal.…”

Treatment of epilepsy: existing therapies and future developments

“…In recent years, some monotherapy trials have been conducted, in restricted circumstances (264). For example, felbamate was studied in placebo-controlled monotherapy trials in patients following pre-surgical electroencephalographic and video monitoring (295)(296)(297). In these trials, the patients underwent intensive neurodiagnostic monitoring after partial or complete withdrawal from their prior AEDs.…”