Clobazam as Add-on Therapy in Children with Epileptic Encephalopathy

Abstract

ABSTRACT:Rationale:Clobazam has been used successfully in adults and children with partial epilepsy. The purpose of this study was to evaluate the safety and efficacy of clobazam as add-on therapy in children with epileptic encephalopathy.Methods:This was a retrospective study conducted at the pediatric epilepsy clinic of our university hospital. Children less than 18-years of age with epileptic encephalopathy were included in the study. Clobazam was introduced as add-on therapy, starting with 5 mg/Kg/day and increased in minimally effective doses, up to the maximum tolerated dose. Data were obtained from clinical files and follow-up visits.Results:Ninety-seven patients were included in the study (39 girls), aged between 1 and 17-years-old (mean = 9.9). Twenty-six patients had Lennox-Gastaut syndrome, seven had myoclonic astatic epilepsy, nine had West syndrome and, in 57 patients, the type of epileptic encephalopathy could not be determined. Clobazam dosage ranged from 5 to 60 mg/day (mean = 37.5 mg/day). Forty (41%) patients presented with adverse events, most of which were mild and transitory, and clobazam needed to be withdrawn in only 11 patients. Nine (9.2%) patients were seizure-free after clobazam adjunctive therapy. In 11 (11.3%) patients seizure improvement was >75%, in 16 (16.5%) it was >50%, in 17 (17.5%) improvement was <50% and in 44 (45.5%) there was no change in seizure frequency. Three patients were lost to follow-up. In 85% of the patients with seizure improvement, the results lasted for more than one year.Conclusion:Clobazam is safe and effective in the treatment of epileptic encephalopathies of childhood.

Clobazam for the Treatment of Intractable Epilepsy in Children

“…Many studies have demonstrated that when a response to clobazam is present, the majority of patients experience significant (i.e., >90%) reduction in seizure frequency. 2,7,11 We found that 60% to 84% of responders reported reduction in seizure frequency >90%. In our cohort of medically intractable patients, such a remarkable reduction in seizure frequency is impressive.…”

“…Seizure freedom on clobazam therapy has been reported in 12% to 26% of patients with localization-related epilepsy and 9% to 40% of patients with generalized epilepsy, similar to our seizure-free rate of 11%. [6][7][8][11][12][13] Age at epilepsy onset, epilepsy duration, patient age, gender, and etiology of epilepsy had no impact on outcome. These are important findings, given clobazam is approved in the United States to treat seizures associated with Lennox-Gastaut syndrome in children aged >2 years.…”

“…Several other studies have demonstrated the efficacy of clobazam for a variety of epilepsy syndromes and etiologies beyond Lennox-Gastaut syndrome. [6][7][8]11,[14][15][16] Eighty-five percent of the patients included in this study had a diagnosis other than Lennox-Gastaut syndrome and 9.3% were younger than 2 years of age.…”

Clobazam as an adjunctive therapy in treating seizures associated with Lennox–Gastaut syndrome

“…Two retrospective studies on the efficacy of clobazam as addon therapy for pediatric patients also reported significant reductions in seizure frequency84,85 (Table 1). Da Silveira et al84 evaluated 100 patients who received clobazam as addon therapy for refractory focal epilepsy, and 33% of these patients had a 75% or greater decrease in seizure frequency.…”

“…Da Silveira et al84 evaluated 100 patients who received clobazam as addon therapy for refractory focal epilepsy, and 33% of these patients had a 75% or greater decrease in seizure frequency. Silva et al85 reviewed the efficacy of clobazam as addon therapy for 97 pediatric patients with epileptic encephalopathies. Of the patients in this study, 28 had LGS.…”