Abstracts

Zonisamide (ZNS) is a broad-spectrum antiepileptic drug (AED) with multiple mechanisms of action. The drug has been available in Japan since 1989 and has been used to treat a variety of seizure types. In the USA, ZNS has been approved for add-on-therapy in adult patients with partial epilepsy since 2000. Few data are available regarding the effects of ZNS in pediatric patients with medically refractory epilepsy. This chart review study investigates the efficacy of ZNS in 50 pediatric patients of this category. This study includes pediatric patients with medically refractory epilepsy treated with ZNS between October 2001 and April 2004. Patients in whom adequate trials of two or more first-line AEDs had failed were defined as medically refractory. We included patients with generalized and partial epilepsy. The efficacy was assessed by caregiver reports and by seizure diaries. Safety and tolerability were assessed by reports of adverse effects. The charts of 50 patients (30 boys, 20 girls) were reviewed. Mean age by epilepsy debut was 2.2 years (range [lt] 1 month to 9 years). Forty-two patients had generalized epilepsy, 8 had partial seizures. Mean age when ZNS-therapy was started was 7.2 years (range 3 months to 17 years). Forty-nine patients received ZNS as add-on therapy, one as monotherapy. Mean dosage was 5.4 mg/kg/d (range 2-12 mg/kg/d). A reduction in seizure frequency of at least 50% was seen in 22 patients, but the efficacy diminished in 10 patients 2 to 6 months after onset of ZNS-therapy. Eight had a significant reduction of one seizure type (5 with myoclonic seizures, 3 with tonic-clonic seizures). Twelve of the patients had no effect of ZNS. Eight patients got a higher seizure frequency at a dosage of 2 mg/kg/d. After withdrawal of ZNS, the previous seizure frequency was restored. In most cases, the tolerability was good. Twenty-three patients had no negative adverse effects. Weight loss because of decreased appetite and vomiting was observed in 4 patients. Others had intermittent drowsiness (n=7), restlessness (n=4), decreased appetite without significant weight loss (n=2), rash (n=1). Data from this cohort suggest that ZNS can be useful in patients with medically refractory epilepsy, especially in patients with generalized epilepsy, in contrast to the approved medical use. Generally, the tolerability was good. Onset of adverse effects was seen already at low-dose-ZNS (2 mg/kg/d). About 25% had no reduction in seizure frequency on ZNS-therapy. Controlled studies of the use of ZNS in pediatric patients are needed.