Abstracts

Pregabalin is an alpha-2-delta ligand with anticonvulsant, analgesic, and anxiolytic properties that in clinical trials has been shown to be efficacious as adjunct treatment for partial seizures with or without secondary generalizations. We investigated the efficacy, safety, and tolerability of pregabalin in a large patient cohort formed by combining data from the fixed-dose arms of 4 clinical trials. The efficacy of pregabalin to reduce partial seizures with or without secondary generalizations was studied using data from four similarly designed, 12-week, double-blind, randomized, multi-center, placebo-controlled trials involving 1174 patients with epilepsy highly refractory to treatment (185, 90, and 532 patients received fixed doses of pregabalin 150, 300, and 600mg/day, respectively, while 367 patients received placebo). All participating patients were refractory to treatment, which was defined as having a history of failing two or more AEDs and inadequately controlled seizures while receiving 1 to 3 concurrent marketed AEDs. The primary efficacy measure was the percent reduction in seizure frequency compared to baseline. Treatment efficacy was also assessed by measuring the proportion of patients who experienced seizure reductions [ge]50% (responders). In all the trials, patients treated with add-on pregabalin consistently reported reductions in seizure frequency that were significantly greater than the reductions reported by patients on placebo. Seizure frequency reductions were positively correlated with dose. Patients receiving adjunctive fixed doses of pregabalin 150, 300, and 600mg/day reported seizure-frequency reductions of 22%, 37%, and 44%, respectively, compared to only 2% by patients receiving placebo. Overall, 22%, 40%, and 46% of patients receiving add-on pregabalin 150, 300, and 600mg/day were responders compared to 10% of patients on placebo (P[le]0.001). Adverse events (AEs) associated with fixed doses of pregabalin treatment were generally dose-related, mild to moderate, and tended to resolve with treatment. Dizziness and somnolence were the two most common AEs. In most cases, AEs did not result in study discontinuation (6% of placebo and 19% of pregabalin patients discontinued). Pregabalin was found to be efficacious and well-tolerated as add-on treatment for partial seizures with or without secondary generalizations throughout the therapeutic dose range and with a clear dose-response relationship. Treatment with pregabalin at the highest dose yielded [ge]50% reductions in seizure frequency in up to 46% of the patients. (Supported by Pfizer Inc.)