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Topiramate
1Department of Neurology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Insights
Topiramate (TPM) shows promise for treating pediatric epilepsies, with preliminary studies indicating effectiveness across various seizure types. Further controlled trials are needed to confirm these findings for children with epilepsy.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Epileptology
Background:
- Emerging clinical evidence suggests topiramate (TPM) efficacy in pediatric epilepsies.
- Pharmacokinetic studies indicate linear pharmacokinetics in children up to 9 mg/kg/d.
- Children exhibit higher oral clearance and lower steady-state plasma TPM concentrations compared to adults.
Purpose of the Study:
- To evaluate the effectiveness of topiramate as adjunctive therapy in pediatric epilepsy syndromes.
- To assess TPM's efficacy in Lennox-Gastaut syndrome, primary generalized tonic-clonic seizures, and refractory partial-onset seizures.
- To explore the potential of TPM monotherapy as a substitute for other antiepileptic drugs in children.
Main Methods:
- Ongoing double-blind, placebo-controlled trials for adjunctive TPM therapy.
- Analysis of preliminary results from pilot studies and open-label extension phases.
- Evaluation of TPM monotherapy substitution in select pediatric epilepsy cases.
Main Results:
- Preliminary data suggest TPM is effective as adjunctive therapy for a wide range of seizure disorders in children.
- In open-label extensions, 47% of Lennox-Gastaut syndrome patients, 64% with partial-onset seizures, and 67% with primary generalized tonic-clonic seizures showed ≥50% seizure reduction.
- Initial findings indicate successful substitution of TPM monotherapy for other antiepileptic drugs in some pediatric cases.
Conclusions:
- Topiramate demonstrates potential as an effective treatment for various pediatric epilepsy types.
- Adjunctive topiramate therapy shows significant seizure reduction in children with Lennox-Gastaut syndrome, partial-onset seizures, and primary generalized tonic-clonic seizures.
- Further well-controlled trials are essential to confirm the efficacy of topiramate in pediatric epilepsies.
Abstract:
Clinical evidence is emerging that topiramate (TPM) may be effective in pediatric epilepsies. Topiramate pharmacokinetics appear to be linear in children when administered in dosages up to 9 mg/kg/d. Mean oral clearance is 44% to 54% higher in children when compared with historical data from adults; steady-state plasma TPM concentrations for the same mg/kg dose are expected to be 33% lower in children. While double-blind, placebo-controlled trials of adjunctive TPM therapy in Lennox-Gastaut syndrome, primary generalized tonic-clonic seizures, and refractory partial-onset seizures in children are ongoing, preliminary results of pilot studies and the open-label extension phases of these double-blind studies suggest TPM may be effective as adjunctive therapy in a broad range of seizure disorders. In the open-label extension phase of a double-blind trial, the proportion of patients with Lennox-Gastaut syndrome experiencing 50% or greater reduction in seizures was 47%. Likewise, seizures were reduced 50% or more with TPM adjunctive therapy in 64% of children with partial-onset seizures and in 67% of patients with primary generalized tonic-clonic seizures treated with open-label during the extension phase of two separate double-blind studies. Preliminary experience suggests that TPM monotherapy can be successfully substituted for another antiepileptic drug in some children. The results of the well-controlled trials are needed to confirm these preliminary observations of TPM effectiveness in pediatric epilepsies.