INCREASED SEIZURE FREQUENCY ASSOCIATED WITH FELBAMATE WITHDRAWAL IN ADULTS

Objective: To characterize changes in seizure frequency following felb amate withdrawal. Design: Nonrandomized, retrospective chart review of a case series. Setting: Epilepsy program specializing in adults with uncontrolled epilepsy. Patient Population: Forty-five ambulatory patie nts withdrawn from felbamate use. Patients were included if they had r eceived felbamate for at least 1 month, were 18 years or older, had ac curate seizure frequency documentation, had accurate documentation of all antiepileptic drugs, and received the same concomitant antiepilept ic drugs before and after felbamate therapy, except for the possible a ddition of gabapentin. Patients were excluded if they had hematologic or hepatic toxic effects with felbamate, were unable to withdraw from felbamate treatment, had a progressive neurologic disorder, or partici pated in another drug trial. Methods: When information became availabl e on aplastic anemia and hepatotoxicity associated with felbamate, all patients were advised to taper their felbamate dosage over approximat ely 2 weeks. They received written instructions for tapering felbamate and adjusting concomitant antiepileptic drugs and kept calendars to n ote the number of seizures. The charts of all patients who received fe lbamate were evaluated for adherence to inclusion and exclusion criter ia. Statistical analysis were performed using a log-linear model for c ount data. Main Outcome Measures: Seizure frequency during the 6 month s before initiating felbamate therapy served as the baseline. Changes in seizure frequency were evaluated by comparing the number of seizure s in the month felbamate was tapered and the 3 months after felbamate discontinuation with the baseline frequency. Comparisons were made bet ween patients who started gabapentin therapy and those who did not and between felbamate responders and nonresponders. Results: Felbamate wi thdrawal resulted in a significant (P=.02) increase in seizure frequen cy. Patients receiving gabapentin had a smaller increase in seizure fr equency, but the difference was not statistically significant. There w as no statistically significant difference in seizure frequency betwee n felbamate responders and nonresponders. Conclusions: Felbamate withd rawal caused a significant increase in seizure frequency over the subs equent 3 months. These findings are important for clinical trial desig n and clinical practice.