Effectiveness and safety of high-dose oral phenobarbital in children with recurrent and treatment-refractory seizures

Abstract

In this study, we applied high-dose oral phenobarbital (PB) to children with recurrent and treatment-refractory seizures or recurrent status epilepticus and evaluated the effectiveness and safety of this treatment. We retrospectively reviewed patients' medical records who received oral high-dose PB treatment between January 2019 and July 2024. In this study, recurrent and treatment-refractory seizures was defined as the persistence of daily epileptic seizures or recurrent attacks of status epilepticus despite treatment with oral antiepileptic drugs or continuous intravenous midazolam therapy. High-dose oral PB therapy was performed on 11 patients (7 females and 4 males). The median age at the onset of epilepsy was 2 months (range: 0.06-132 months). The underlying disorders or comorbidity were genetic disorders (1q14 del, compound heterozygous for the PNKP gene, Wolf-Hirschhorn syndrome, ring chromosome 14 syndrome) in 4 patients, cerebral palsy in 2 patients, metabolic disorders (Zellweger syndrome, pyridoxine-dependent epilepsy) in 2 patients, traumatic brain injury and hypoxia, hemimegalencephaly, and ataxia and intellectual disability in 1 patient. The median age at initiation of high-dose PB therapy was 11 months (range: 2-203 months). The maximal dose of PB ranged from 6 to 14.7 mg/kg/d (median: 10 mg/kg/day). The maximal serum PB levels ranged from 33 to 56 mu g/mL (median: 44 mu g/mL). We evaluated the effectiveness of this treatment as follows: "effective" represented more than 50% seizure reduction, "ineffective" represented less than 50% seizure reduction, and "exacerbation" represented an increase in seizure frequency. In 7 of the 11 patients (63.6%), oral high-dose PB therapy was effective and was transiently effective in the other 4 patients. Adverse effects were noted in 6 patients (54.5%) during high-dose oral PB therapy: drowsiness in 5 patients and mild elevations in transaminases in 2 patients.