A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures

Purpose: This study assessed the comparative efficacy of pregabalin for refractory partial seizures. Methods: Four-hundred and thirty-four patients with partial seizures were randomized to pregabalin, lamotrigine, or placebo as adjunctive therapy for 17 weeks of double-blind treatment. In phase I (11 weeks), pregabalin was titrated over 1 week and lamotrigine over 5 weeks to fixed dosages of 300 mg/day for both. In phase II (6 weeks), patients not yet seizure-free were increased to pregabalin 600 mg/day or lamotrigine 400 mg/day. Results: During phase I, there was a nonsignificant trend toward a greater reduction in seizures with pregabalin versus placebo and lamotrigine. Across the 17 weeks of treatment, pregabalin showed a median percentage reduction from baseline in seizure frequency of -20.0% (p = .001) versus placebo, and -9.7% (p = .080) versus lamotrigine. The responder rate (>= 50% reduction in seizure frequency) for pregabalin exceeded that of placebo (36% vs 21%; p = .007) and lamotrigine (36% vs 24%; p = .04). Adverse events were consistent with the known safety profiles of pregabalin and lamotrigine. Discussion: Pregabalin was demonstrated to be noninferior to lamotrigine in the treatment of refractory partial seizures. Overall conclusions were complicated by an unusually large and heterogeneous placebo response. (C) 2010 Published by Elsevier B.V.