Pregabalin for the management of partial epilepsy

Philippe Ryvlin¹, Emilio Perucca², Sylvain Rheims¹

¹Service de Neurologie et d’Epileptologie, Hôpital Neurologique, Hospices Civils de Lyon, Université Lyon 1, INSERM U821 and CTRSIDÉE, Lyon, France; ²Clinical Trial Centre, Institute of Neurology IRCCS C Mondino Foundation, and Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

Abstract: Pregabalin is one of the latest antiepileptic drugs introduced for the treatment of partial epilepsy. Its efficacy and safety as adjunctive therapy in refractory partial epilepsy have been established in four double-blind placebo-controlled trials (n = 1396) and 4 long-term open-label studies (n = 1480). In 3 fixed-dose trials, the proportion of patients with a ≥50% reduction in seizure frequency across the effective dose-range (150–600 mg/day) ranged between 14% and 51%, with a clear dose-response relationship. Suppression of seizure activity could be demonstrated as early as day 2. The most frequently reported CNS-related adverse events included dizziness, somnolence, ataxia and fatigue, were usually mild or moderate, and tended to be dose related. In long-term studies, weight gain was reported as an adverse event by 24% of patients. When pregabalin dose was individualized to according to response within the 150 to 600 mg/day dose range, tolerability was considerably improved compared with use of a high-dose, fixed-dose regimen (600 mg/day) without titration. In long-term studies up to 4 years, no evidence of loss efficacy was identified. During the last year on pregabalin, 3.7% of patients were seizure-free. Pregabalin appears to be a useful addition to the therapeutic armamentariun for the management of refractory partial epilepsy.

Keywords: pregabalin, antiepileptic drugs, adjunctive therapy, partial seizures, efficacy, tolerability, clinical trials