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

Only four randomised controlled trials have been undertaken assessing add-on clobazam for refractory epilepsy. All are cross-over studies of short duration; they used differing designs and were of poor methodological quality. Results suggest that clobazam reduces seizure frequency for drug refractory partial epilepsy. There are limited and inconclusive data for generalized epilepsy. Cloabazam was also associated with adverse events.

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.

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Epilepsy effects approximately 1% of the population, with up to 30% of patients continuing to have seizures despite antiepileptic drug treatment.


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.