Monotherapy trials with gabapentin for partial epilepsy.

The efficacy and safety of gabapentin as monotherapy for treatment of partial onset seizures were evaluated in three large multicenter, double-blind, parallel-group, dose-controlled trials. In the first trial, 275 outpatients with refractory partial epilepsy maintained on stable doses of one or two antiepileptic drugs (AEDs) were switched to gabapentin (GBP) monotherapy at 600 mg, 1200 mg, or 2400 mg daily. Patients were required to exit the 26-week double-blind phase of the study if they experienced worsening of seizure frequency. With respect to time to exit, there was no statistically significant difference among the three groups; only 3% of patients withdrew from the trial because of adverse events. In the second study, 82 hospitalized patients with medically refractory epilepsy were tapered off baseline AEDs and randomly assigned to GBP monotherapy at 300 mg/day or 3600 mg/day. Patients remained in the trial for a maximum of 8 days but had to exit the trial if they experienced one or more exit events. Time to exit was significantly longer in patients in the 3600-mg group (151 h) compared with those in the 300-mg group (85 h) (p = 0.0001). None of the patients withdrew from the trial because of side effects. In the third study, 292 patients with newly diagnosed partial seizures were randomized to GBP 300, 900, or 1800 mg/day or to carbamazepine (CBZ) 600 mg/day. Patients remained in the trial for up to 6 months or until they experienced an exit event. Mean time to exit was significantly longer for patients who received GBP 900 mg/day (p = 0.02) or 1800 mg/day (p = 0.04) compared with those who received 300 mg/day. The completion rate for the CBZ group (37%) was similar to that of the GBP 900-mg (39%) and 1800-mg (38%) groups. Patients receiving CBZ had a higher withdrawal rate because of adverse events compared with the GBP 900-mg and 1800-mg groups. The results of these trials provide good evidence of the efficacy and safety of GBP as monotherapy for the treatment of partial-onset seizures.