Effectiveness of topiramate in eleven patients with Dravet syndrome

Abstract Dravet syndrome is a rare, but highly refractory epilepsy syndrome. As conventional drugs are not effective, introduction of new effective drugs in clinical use will benefit patients with this disease. We assessed the effectiveness of topiramate (TPM) as adjunctive therapy in 11 patients with Dravet syndrome. TPM was started at doses ranging from 10 to 50 mg/day (0.57 to 2.0 mg/kg/day), and the dosage was increased gradually up to the maximum dose (9 mg/kg/day) depending on efficacy and tolerability. The frequencies of convulsive seizures (generalized tonic-clonic seizures, unilateral seizures, partial onset generalized tonic-clonic seizures) during two months before starting TPM, two months after starting TPM, and the fifth and sixth months after starting TPM were determined. The mean dose (mean +/- SD) of TPM at the second month was 2.7 +/- 1.5 mg/kg/day (1.0-5.7 mg/kg/day, n= 11), and that at the sixth month was 4.5 +/- 2.2 mg/kg/day (1.0-7.3 mg/kg/day, n=10). Evaluation at the second month revealed that one of 11 patients (9%) became seizure-free, six patients (54%) showed greater than 50% seizure reduction, three patients (27%) showed less than 50% seizure reduction, and one patient (9%) had aggravation of convulsive seizures resulting in discontinuation of TPM at the first month. Evaluation at the sixth month revealed that one of 10 patients (10%) was seizure-free, seven patients (70%) had greater than 50% seizure reduction, two patients (20%) had less than 50% seizure reduction, and no patient (0%) had aggravation. Adverse effects were observed in five patients; dizziness in three patients, sleepiness in three patients, and oligohidrosis in one patient. In the present study, TPM was useful as an adjunctive therapy to reduce the frequency of convulsive seizures in patients with Dravet syndrome. A large-scale efficacy study of TPM for Dravet syndrome is warranted.