Clobazam in pediatric drug-resistant epilepsy: from pharmacology to clinical practice.

OBJECTIVE: To systematically review the current research progress on clobazam in pediatric antiepileptic therapy, focusing on its pharmacological mechanisms, pharmacokinetic properties, clinical efficacy, safety profile, and approaches to individualized treatment, with particular emphasis on the influence of CYP2C19 genetic polymorphisms on pharmacokinetics and therapeutic outcomes, and to provide a comprehensive reference for the rational clinical use of clobazam. METHODS: This article comprehensively reviews the current research progress on clobazam in pediatric antiepileptic therapy, including evidence of efficacy across different epilepsy syndromes, strategies for managing drug-drug interactions, and individualized dosing regimens based on genotyping and therapeutic drug monitoring. RESULTS: Clobazam is a 1,5-benzodiazepine used as an antiseizure medication. Compared with classical 1,4-benzodiazepines, it demonstrates greater efficacy and fewer sedative adverse effects. Clobazam was approved by the U.S. Food and Drug Administration (FDA) in 2011 as an adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥2 years. Since then, it has been increasingly used as adjunctive therapy for several pediatric epilepsy syndromes, including Dravet syndrome (DS), epilepsy with myoclonic-atonic seizures (EMAS), and epileptic encephalopathy with spike-wave activation during sleep. CYP2C19 genetic polymorphisms significantly influence its pharmacokinetics and therapeutic outcomes. Across the reviewed studies, adjunctive clobazam achieved ≥50% seizure reduction in approximately 53% of children and seizure freedom in approximately 24%. Efficacy was highest in LGS, supported by randomized controlled trials, while evidence for other syndromes was largely observational. CYP2C19 poor metabolizer status significantly increased N-desmethylclobazam exposure, supporting genotype-guided dose initiation. CONCLUSION: Clobazam demonstrates consistent efficacy as adjunctive therapy in pediatric drug-resistant epilepsy, with the strongest evidence supporting its use in LGS. Individualized treatment informed by CYP2C19 genotyping and therapeutic drug monitoring can optimize clinical outcomes. This review provides a comprehensive reference for the rational clinical use of clobazam.