• Karla Hemming, Melissa J Maguire, Jane L Hutton, and Anthony G Marson.
• Department of Statistics, University of Warwick, Coventry, UK, CV4 7AL. karla@stats.warwick.ac.uk
• Cochrane Db Syst Rev. 2008 Jan 1(3):CD007302.

BackgroundEpilepsy is a common neurological condition which affects between 0.5% and 1% of the population. Approximately 30% of people with epilepsy do not respond to treatment with currently available drugs, and the majority of these people have partial epilepsy. Vigabatrin is an antiepileptic drug licensed for use in the treatment of refractory epilepsy. No major side effects associated with the use of vigabatrin were detected by initial randomised controlled trials of the drug. However, longer term observational studies have subsequently identified that its use is associated with asymptomatic visual field constriction.ObjectivesThe objective of this review is to synthesise evidence from short-term, randomised, placebo-controlled trials of vigabatrin. We summarise the effects of vigabatrin on seizures and short-term side effects when used as an add-on treatment for people with drug-resistant partial epilepsy. A review of longer term observational studies and estimates of proportions of patients developing visual field constrictions is currently being undertaken and results will be cited here in due course.Search StrategyWe searched the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1950-March 2008), and reference lists of articles. We also contacted the manufacturers of vigabatrin (Hoechst Marion Roussel).Selection CriteriaWe included randomised, double-blind, placebo-controlled, fully published trials of vigabatrin, in people with drug-resistant partial epilepsy.Data Collection And AnalysisTwo review authors assessed trials for inclusion and extracted data. Primary analysis was by intention-to-treat (ITT). Outcomes evaluated included 50% or greater reduction in seizure frequency, treatment withdrawal and side effects observable in the short term. Results are presented on the relative risk (RR) scale with 95 or 99% confidence intervals (CI).Main ResultsEleven suitable trials, testing doses between 1000 mg and 6000 mg, were identified and included in the analysis. There were 982 observations on 747 patients in the primary ITT analysis of treatment efficacy. Patients treated with vigabatrin were significantly more likely to obtain a 50% or greater reduction in seizure frequency compared with those treated with placebo (RR 2.58 (95% CI 1.87 to 3.57)). Those treated with vigabatrin were also significantly more likely to have treatment withdrawn (RR 2.49 (95% CI 1.05 to 5.88)), and more likely to experience a number of side effects, significantly so for fatigue or drowsiness. There was some evidence of small study effect bias, with smaller studies tending to report greater estimates of RR than larger studies. It is possible that the actual relative risk of obtaining 50% reduction in seizure frequency may therefore be less than that obtained by a meta-analysis of fully published studies.Authors' ConclusionsThis review of randomised controlled trials shows that vigabatrin can reduce seizure frequency in people with drug-resistant partial epilepsy. Short-term follow up of patients shows some side effects are associated with its use. Further analysis of longer term observational studies is required to evaluate how likely patients are to develop visual field defects, and whether such side effects are associated with dose and duration of drug use.

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