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.