Efficacy and Tolerability of Clobazam in Adults With Drug-Refractory Epilepsy

Abstract

ObjectivesTo evaluate the effectiveness and tolerability of clobazam as an adjunctive treatment for adults with drug-resistant epilepsy.MethodsWe performed a single-center, retrospective chart review of patients ≥18 years of age with drug-resistant epilepsy who started clobazam between 2010 and 2018. Included patients had outpatient visits both before and ≥1 month after clobazam initiation. Epilepsy classification, seizure frequency before and after clobazam, duration of clobazam treatment, and adverse effects were analyzed.ResultsA total of 417 patients met inclusion criteria. Mean age was 37.5 years, and 54% of patients were female. Patients were on a mean of 2.4 antiepileptic drugs at time of initiation of clobazam. Epilepsy types were focal (56.8%), Lennox-Gastaut syndrome (LGS) (21.1%), generalized (15.1%), and unclassified (7.0%). At the first follow-up visit ≥1 month after clobazam initiation, 50.3% of patients had >50% reduction in seizure frequency, and 20.5% were seizure-free. Of the initial cohort, 17.1% were followed >1 year and were seizure-free at last follow-up. Response rates did not differ between different epilepsy classifications. Fifty-one percent of patients experienced ≥1 side effect, most commonly lethargy/fatigue (30.7%) or mood changes (10.8%). A total of 178 (42.6%) patients discontinued clobazam, most commonly due to adverse effects (55%).ConclusionsClobazam is effective and safe as a long-term adjunctive therapy for adults with drug-resistant epilepsy; efficacy in off-label use is similar to that in LGS.Classification of evidenceThis study provides Class IV evidence that clobazam is an effective treatment for adults with drug-resistant epilepsy, independent of epilepsy classification.

A comprehensive systematic literature review of the burden of illness of Lennox–Gastaut syndrome on patients, caregivers, and society

“…Seizure frequency ranged widely within and across studies, which may be partly owing to interindividual heterogeneity; in one study, baseline seizure frequency was 15–3000 seizures per month 46,51 . These findings aligned with those from studies in which individuals were categorized by seizure frequency; 50%–100% of individuals were reported to have daily seizures, and those without daily seizures were usually reported to have seizures at least once per week 18,20,23,26,28,34–36,52–58 …”

“…These four studies covered relatively small samples of children from Italy, Nepal, South Korea, or the USA, but did suggest pharmacoresistance in LGS is not limited to a particular pediatric age group or geographical location. Polytherapy is usually required, 26,30,60,97,105 with concurrent use of 2–4 ASMs per individual with LGS reported across approximately 40 studies 18,28,34,36–39,42,44,48–51,53–55,58,66,68,72,73,78,80,81,83,88,90,95,96,98–100,102,104,108–111 . Exceptions to the finding that 2–4 ASMs are used concurrently by individuals with LGS were reported in some studies.…”

“…46,51 These findings aligned with those from studies in which individuals were categorized by seizure frequency; 50%-100% of individuals were reported to have daily seizures, and those without daily seizures were usually reported to have seizures at least once per week. 18,20,23,26,28,[34][35][36][52][53][54][55][56][57][58] Several prospective and retrospective studies showed decreases in seizure frequency over time, reporting similar ranges of seizure freedom prevalence at last visit (9%-28% and 4%-28%, respectively). 17,20,34,38,43,47,[59][60][61][62][63][64][65][66][67] Although the duration of data collection varied considerably between studies (3-20 years), no correlation between the change in seizure frequency and the duration of data collection was observed.…”

Update on Antiseizure Medications 2022

“…Class IV evidence of efficacy in adjunctive treatment of drug-resistant focal epilepsy and idiopathic generalized epilepsy has been reported. 52…”

“…The clobazam FDA indication is for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients 2 years of age or older. Class IV evidence of efficacy in adjunctive treatment of drug-resistant focal epilepsy and idiopathic generalized epilepsy has been reported 52 …”