Clobazam is an effective, well-tolerated agent with a high seizure-free rate and a significant seizure reduction rate in the pediatric population, according to a retrospective, multicenter cohort study published in the journal Epilepsy Research.
The researchers sought to evaluate the efficacy and tolerability of clobazam, a benzodiazepine, among pediatric patients with respect to seizure semiology, epileptic seizure, and etiology-specific epileptic seizures. The present study, which was conducted between 2015 and 2021 in 8 centers located in 7 geographic regions in Turkey, included patients 0 to 17 years of age. Clobazam treatment needed to be maintained for 12 months or longer among those patients reported to have experienced benefits from the therapy. The availability of an initial electroencephalogram (EEG) recording, as well as follow-up recordings, was required among all participants. The initial efficacy of the agent was assessed after 3 months of treatment.
Patients were classified as follows: (1) those with a >50% decrease in seizure frequency were defined as “>50% responders”; (2) individuals with a <50% decrease in seizure frequency were defined as “<50% responders”; (3) those with no change in the number of seizures were defined as “nonresponders”; (4) individuals with an increase in the number of seizures were defined as “negative responders”; and (5) those who reported experiencing no seizures for >6 months were defined as “seizure-free.”
A total of 1710 patients were included in the study. The most common type of seizure reported was generalized tonic clonic in 27% (462 of 1710) of patients; the most common type of epileptic syndrome was West syndrome in 17.5% (300 of 1710) of the participants.
When the initial efficacy was analyzed after the first 3 months of clobazam therapy, seizures had ceased entirely in 18.7% of patients. Further, a decrease in seizures of >50% was reported in 39.9% of participants, a decrease in seizures of <50% in 17.4% of patients, no response in 21.5% of participants, and an increase in seizures among 2.5% of patients. EEG improvement was established in 55.7% of participants, and full recovery was determined in 7.5% of patients based on their initial EEG recordings.
Seizure-control rates were classified as follows: (1) positive response (ie, seizure-free and >50% response); (2) partial positive response; and (3) and negative response (ie, no change or worse). No significant differences in seizure response were observed with respect to gender or age. Regarding the etiology of specific epilepsy syndromes, “the highest negative response rate was observed in the genetic and metabolic causes group.” The group who experienced generalized onset seizures exhibited a significantly higher partial positive response rate compared with the group who experienced epileptic spasms (P <.010).
The highest positive response rate among the epileptic syndromes was in those with self-limited epilepsy with centrotemporal spikes. Further, the highest negative response rate was for developmental and/or epileptic encephalopathies.
Regarding magnetic resonance imaging (MRI) results, patients with normal MRIs and those with acquired lesions exhibited more positive responses than those with congenital anomalies. Additionally, the negative response rate in patients with congenital lesions was significantly higher than that in participants with normal MRIs (P =.001). MRI revealed a structural etiological diagnosis in 25.8% of the patients.
The positive response rate in those who used 1 or 2 antiseizure medications was higher than the rate in the group that used 3 or more antiseizure medications, whereas the negative response rate also was significantly higher in the group that used 3 or more antiseizure medications (P <.001). The most common EEG change in the positive response group was an improvement of more than 50%. Further, the highest negative response rate was in the group with no EEG change (P <.001).
The current study has several limitations. The number of patients who received monotherapy was very small because of the selection characteristics for clobazam in the pediatric population. Further, no clear single protocol for dosage adjustment or standardization of starting doses was specified. Another major limitation was the lack of a full spectrum of well-defined epileptic syndromes with a definitive etiological diagnosis that was supported by next-generation genetic testing.
According to the researchers, “Future prospective studies, including genetically well-defined etiological subgroup analysis, will yield more accurate data concerning the effectiveness and tolerability of clobazam monotherapy and add-on therapy in pediatric age groups.”
Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.
Kamaşak T, Serdaroğlu E, Yılmaz Ö, et al. The effectiveness and tolerability of clobazam in the pediatric population: adjunctive therapy and monotherapy in a large-cohort multicenter study. Epilepsy Res. Published online June 6, 2022. doi:10.1016/j.eplepsyres.2022.106963