Zonisamide for absence seizures
Introduction
Zonisamide (Zonegran®) was approved in the United States in 2000 for the adjunctive treatment of partial seizures in adults with epilepsy. Its efficacy and safety in the treatment of partial seizures was established in three pivotal clinical trials in the United States and Europe (Sackellares et al., 2004, Schmidt et al., 1993, Faught et al., 2001). However, the drug displays multiple mechanisms of action, suggesting that it may be useful in treating a variety of seizure types, including absence seizures. Specifically, zonisamide's blockage of T-type calcium channels (Suzuki et al., 1992) may confer efficacy in absence seizures, as research has implicated T-type calcium channel activation as a key component in the genesis of absence seizures (Futatsugi and Riviello, 1998, Kim et al., 2001).
There are few published reports regarding zonisamide therapy in patients with absence seizures. Reports from Japan, where zonisamide has been available since 1989, describe clinical success in the treatment of absence seizures in small case series (Yagi and Seino, 1992, Kotani et al., 1994). Additionally, small open-label and case studies in the United States have suggested efficacy of zonisamide in patients with absence seizures (Reigle et al., 2001, Andriola et al., 2002, Hershkowitz, 2002). To further extend the present body of knowledge surrounding zonisamide and absence seizures, the present chart review study examines the response of young patients with absence seizures to zonisamide therapy.
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Methods
Patients with typical and atypical absence seizures associated with various epilepsy syndromes from the Blue Bird Circle Clinic for Pediatric Neurology at Texas Children's Hospital, a comprehensive epilepsy center, who were treated with zonisamide between November 2001 and November 2003 were identified. Patient charts were reviewed for demographic characteristics, previous and concomitant antiepilepsy drug (AED) therapy, zonisamide dosage, duration of zonisamide therapy, subjective patient and
Demographic and treatment characteristics
The chart review identified 45 patients (24 female, 21 male) aged 18 years or younger who were treated with zonisamide for absence seizures. Mean patient age was 11.4 years (range, 2.8–17.9 years). Forty patients (88.9%) had received previous therapy with 1 or more other AEDs before starting zonisamide therapy. The mean zonisamide dosage was 343.0 mg/d or 9.0 mg/kg/d (range, 100–600 mg/d or 2–24 mg/kg per day, n = 43), and the mean duration of zonisamide therapy was 64.8 weeks (range, 6–154 weeks; n =
Discussion
There is a paucity of information regarding the use of zonisamide in patients with absence seizures. One analysis of open-label and controlled clinical trials from Japan included 13 patients with absence seizures treated with zonisamide (Yagi and Seino, 1992). Responder rates (i.e., the percentages of patients experiencing a ≥50% reduction in seizure frequency from baseline) were 67% (6/9) for patients with atypical absence seizures and 50% (2/4) for patients with typical absence seizures.
Acknowledgments
This study was funded, in part, by a grant from Eisai Inc. We wish to acknowledge Tammy Christensen, MBA, RHIA, of Texas Children's Hospital for her assistance with this project. We also wish to acknowledge MedLogix Communications, LLC, for providing editorial support.
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2012, Handbook of Clinical NeurologyCitation Excerpt :However, ethosuximide is not appropriate in the presence of any other seizure types, because of its very selective efficacy against absence. Although there are case reports and case series supporting topiramate, zonisamide, and levetiracetam as initial therapy for absence (Cross, 2002; Wilfong and Schultz, 2005; Verrotti et al., 2008), their efficacy still needs to be demonstrated in a prospective trial. No new AED has class I trial data supporting its use as adjunctive therapy for generalized absence seizures.