Effectiveness and Safety of High-Dose Oral Phenobarbital in Children With Recurrent and Treatment-Refractory Seizures
Muhittin Bodur1, Rabia Tutuncu Toker1
1Bursa Uludag University, Pediatric Neurology, Bursa, Turkey.
Insights
High-dose oral phenobarbital (PB) effectively reduced seizures in 63.6% of children with refractory epilepsy. While generally safe, adverse effects like drowsiness were observed in over half of the patients.
Area of Science:
- Pediatric Neurology
- Epileptology
- Pharmacology
Background:
- Recurrent and treatment-refractory seizures pose significant challenges in pediatric epilepsy management.
- Established antiepileptic drugs and therapies often fail to control severe or persistent seizure activity.
- Exploring alternative or high-dose therapeutic options is crucial for improving outcomes in difficult-to-treat epilepsy cases.
Purpose of the Study:
- To evaluate the effectiveness of high-dose oral phenobarbital (PB) in children experiencing recurrent, treatment-refractory seizures or status epilepticus.
- To assess the safety profile and adverse effects associated with high-dose oral PB therapy in this pediatric population.
Main Methods:
- Retrospective review of medical records for 11 pediatric patients treated with high-dose oral PB between January 2019 and July 2024.
- Definition of treatment-refractory seizures: persistence despite standard oral antiepileptic drugs or intravenous midazolam.
- Dosage and serum levels of PB were recorded; effectiveness categorized by seizure reduction (>50% effective, <50% ineffective, seizure increase exacerbation).
Main Results:
- High-dose oral PB therapy was effective in 7 out of 11 patients (63.6%), achieving over 50% seizure reduction.
- Transient effectiveness was observed in the remaining 4 patients.
- Adverse effects occurred in 6 patients (54.5%), primarily drowsiness (5 patients) and mild transaminase elevations (2 patients).
Conclusions:
- High-dose oral phenobarbital demonstrates significant efficacy in a majority of pediatric patients with treatment-refractory epilepsy.
- The treatment is generally well-tolerated, with drowsiness being the most common adverse effect.
- High-dose oral PB represents a viable therapeutic option for severe, refractory pediatric seizure disorders.
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 µg/mL (median: 44 µg/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.
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