Long-term use of zonisamide in refractory childhood-onset epilepsy.

This open label study examined the long-term efficacy and safety of zonisamide as adjunctive therapy in mentally retarded and multiple-handicapped patients with severe childhood-onset epilepsy. The study included 24 patients (mean age 12.5 years, range 2-40 years) which had different severe epilepsy syndromes (75% focal, 12.5% generalized, 12.5% refractory status epilepticus) refractory to at least 6 (median 10) anti-epileptic drugs. All patients were followed for at least 18 months after beginning of zonisamide treatment. Mean duration of zonisamide therapy was 55 weeks (range 5-168 weeks) and mean maintenance dosage was 7.7 mg/kg/day (range: 4-16 mg/kg/day). The patients received an average of 1.9 (range 1-3) concomitant antiepileptic drugs. The initial response rate defined as a > or =50% reduction of seizure frequency after 8 weeks was 58.3% (14 of 24 patients). Four of 14 initial responders developed loss of efficacy during long-term treatment. The retention rate after 18 months was 41.7% (10 of 24 patients). One patient (4.2%) became completely seizure-free after initiation of zonisamide treatment and remained seizure-free for the entire observation period of 18 months. Overall, zonisamide was well tolerated. Side effects were observed in 46% of patients and were mild to moderate. They mostly occurred during titration and subsided in maintenance dosing. Only in two patients (8.3%) zonisamide therapy was discontinued due to side effects (loss of appetite). No serious side effects were observed. These results are similar to the findings of Japanese studies suggesting that long-term use of adjunctive zonisamide therapy may be beneficial for treating mentally retarded, multiple handicapped patients with highly refractory childhood-onset epilepsy.