Pregabalin add-on for drug-resistant partial epilepsy

Abstract

Epilepsy is a common chronic neurological disease with an estimated prevalence of 1% in the United Kingdom. Approximately a third of these people continue to have seizures despite drug treatment. In order to try to improve outcomes a number of new antiepileptic drugs have been developed and pregabalin is one of these. To summarize evidence from randomized, controlled trials regarding the efficacy and tolerability of pregabalin when used as an add-on antiepileptic drug in treatment-resistant partial epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (July 2007), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2007), Medline (1966 to March 2007) and contacted Pfizer Inc (the manufacturers of pregabalin) to identify published, unpublished, and ongoing trials. We included randomized controlled double-blind trials comparing pregabalin with placebo for people with drug-refractory partial epilepsy. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal for any reason, treatment withdrawal for adverse events, and nature of adverse events. Two review authors (DL and AGM) independently selected and assessed suitable trials and extracted data. Primary analyses were by intention-to-treat (ITT). Results are presented as relative risks (RR) with 95% confidence intervals (CI). Four suitable trials (1397 participants) were identified and included in the analysis. Trials tested doses of pregabalin ranging from 50 mg to 600 mg per day. For the primary outcome, 50% or higher seizure reduction was significantly more likely in patients randomized to pregabalin than to placebo (RR 3.56, 95% CI 2.60 to 4.87). A dose response analysis suggested increasing effect with increasing dose. Pregabalin was not significantly associated with seizure freedom (RR 2.73, 95% CI 0.72 to 10.33). Patients were significantly more likely to have pregabalin withdrawn for any reason (RR 1.43, 95% CI 1.11 to 1.85) or for adverse effects (RR 2.47, 95% CI 1.80 to 4.17). Ataxia, dizziness, somnolence and weight gain were significantly associated with pregabalin. Pregabalin, when used as an add-on drug for treatment-resistant partial epilepsy, is significantly more effective than placebo at achieving a 50% or greater seizure reduction. Results demonstrate efficacy for doses from 150 mg to 600 mg per day, with no evidence for plateauing of effect at the doses tested. The trials included in this review were of short duration and longer term trials are needed to better inform clinical decision making.