Clobazam as an add-on in the management of refractory epilepsy

BACKGROUND: Epilepsy effects approximately 1% of the population, with up to 30% of patients continuing to have seizures despite antiepileptic drug treatment. OBJECTIVES: To assess the efficacy and tolerability of clobazam when used as an add-on therapy for patients with refractory partial onset or generalised onset seizures. SEARCH STRATEGY: We searched the following databases: (a) The Cochrane Epilepsy Group Specialised Register (February 2011); (b) The Cochrane Central Register of Controlled Trials (CENTRAL Issue 1, The Cochrane Library 2011); (c) MEDLINE (1948 to January 2011); (d) Database of Abstracts of Reviews of Effectiveness (DARE Issue 1, The Cochrane Library 2011); (e) BIOSIS Previews (February 2011). SELECTION CRITERIA: Randomised trials of add-on clobazam, with adequate methods of allocation concealment, recruiting patients with drug refractory partial or generalised onset seizures, with a minimum treatment period of eight weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: 50% or greater reduction in seizures; seizure freedom; treatment withdrawal and adverse effects. MAIN RESULTS: Four cross-over studies, representing 196 participants, were included. However, due to significant methodological heterogeneity and differences in outcome measures it was not possible to summarise data in a meta-analysis. Only two of the studies reported a 50% or greater seizure reduction compared to placebo; 57.7% and 52.4%. Side effects were only described in two of the studies, reportedly present in 36% and 85% of patients. AUTHORS' CONCLUSIONS: Clobazam as an add-on treatment may reduce seizure frequency and may be most effective in partial onset seizures. However, it is not clear who will best benefit and over what time-frame. A large scale, randomised controlled trial conducted over a greater period of time, incorporating subgroups with differing seizure types, is required to inform clinical practice.