To characterize the local adult drug-refractory epilepsy population and determine the efficacy and tolerability of clobazam in this group.

Drug-refractory epilepsy occurs in approximately 30% of epilepsy patients and is notoriously difficult to treat. After failure of two anti-epileptic drugs (AEDs), only 3% of patients will become seizure-free with additional seizures medications. Clobazam is a promising long-acting benzodiazepine which was FDA-approved for use in Lennox-Gastaut syndrome in 2011. 

1. This was a single center retrospective chart review performed at the Hospital of the University of Pennsylvania. Subjects were >18 years old with drug-refractory epilepsy who were prescribed clobazam between 2010 and 2017. Patients were followed by the Penn Epilepsy Center with outpatient clinic visits both prior to and at least 1 month after initiation of clobazam. Data was collected on baseline demographics and epilepsy severity, as well as seizure frequency after reaching maximum tolerable dose, time to discontinuation, and adverse side effects. Primary outcome measures were rate of >50% seizure reduction and seizure freedom rate. 

417 patients met study criteria. Prior to clobazam, patients were on an average of 2.4 active AEDs and 81.2% had seizures at least once a month. Post-intervention, 50.3% of patients experienced a >50% reduction in seizure frequency and 19.9% achieved seizure freedom, with no statistically significant difference between epilepsy types. 51% of patients experienced at least 1 side effect, most commonly lethargy/fatigue (30.7%) and mood changes (10.8%). A total of 143 (34.2%) patients discontinued clobazam, with the majority (55%) citing adverse effects as the reason for discontinuation.

Clobazam is effective as an adjunctive therapy for adult drug-refractory epilepsy. Rates of seizure reduction and seizure freedom were higher than what has been historically reported for other AEDs. Adverse side effects were common and limited tolerability in a minority of patients.