Zonisamide in children and young adults with refractory epilepsy: An open label, multicenter Italian study
Introduction
The novel antiepileptic drug zonisamide (ZNS) is characterised by a broad range of pharmacological effects associated with multiple mechanisms of action. These include a voltage-sensitive sodium and T-type calcium channel blockade, a reduction in glutamate-mediated synaptic excitation and enhanced inhibitory effects mediated by gamma-aminobutyrric acid (Biton, 2004).
Zonisamide has recently been approved in Europe for the adjunctive treatment of refractory partial seizures in adults. It has been available in Japan since, 1989, with studies there having established that ZNS is effective and safe for use in children (Ohtahara, 2006). Information from other countries concerning its use in pediatric patients is still somewhat limited. There are, however, a growing number of studies reporting the clinical efficacy of ZNS, both as add-on therapy (Kim et al., 2005, Mandelbaum et al., 2005; Santos and Brotherton, 2005; Ohtahara, 2006, Kluger et al., 2008) and as monotherapy (Miura, 2004, Seki et al., 2004, Kim et al., 2005, Kothare et al., 2006) in pediatric generalised and partial seizures.
The aim of this paper is to report on the first multicentre Italian experience with ZNS as an add-on drug for the treatment of refractory generalised and partial epilepsy in children, adolescents and young adults.
Section snippets
Methods
Patients were recruited in a prospective add-on, open-label treatment study from eight Italian centres for pediatric and adolescent epilepsy care. The patients were selected according to the following criteria: (1) age one year and over; (2) partial or generalised epileptic seizures refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination; (3) more than 1 seizure per month in the last 6 months; (4) use of at least one other AED, but no more than two, at
Results
Eighty-two young patients (45 males, 37 females), aged between 3 and 34 years (<6 years: 20.7%; 7–12 years: 35.4%; 13–18 years: 23.2%; >19 years: 20.7%: mean age 13.1 years), all affected by refractory epilepsy, were enrolled in the study. Patient diagnoses were as follows: symptomatic (28) and cryptogenic (19) partial epilepsy; symptomatic (19) and cryptogenic (16) generalized epilepsy (including 2 with Lennox–Gastaut syndrome, 3 with myoclonic–astatic syndrome, 6 with severe myoclonic
Discussion
In this study, ZNS as add-on therapy significantly reduced seizure frequency in approximately half of our patients who had partial or generalised epilepsy that had proved resistant to at least three previous antiepileptic drugs.
Few patients (10.9%), all of whom were in the cryptogenic group, became seizure-free. In addition, ZNS proved to be somewhat more effective in the treatment of partial seizures.
The overall response to ZNS observed in our study is in keeping with that reported in Japanese
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Cited by (28)
Short-term efficacy and safety of zonisamide as adjunctive treatment for refractory partial seizures: A multicenter open-label single-arm trial in Korean patients
2012, SeizureCitation Excerpt :The efficacy and safety of ZNS in partial epilepsy have been demonstrated in several pre-registration, randomized, double-blind, placebo-controlled studies in which this drug was administered as adjunctive therapy in drug-resistant epileptic patients with partial epilepsy.6–9 Long-term open studies as well as double-blind, placebo-controlled studies have demonstrated that ZNS has a good efficacy and tolerability profile, supporting its use as an adjunctive therapy for adult epileptic patients.10–15 A long-term open-label study13 in 317 patients with refractory partial epilepsy who completed a fixed-dose, randomized, double-blind, add-on trial4 showed that patient retention rates at 1, 2, and 3 years were 65.3%, 44.5% and 28.8%, respectively, comparable to those reported for other AEDs.
Antiepileptic drugs
2011, Side Effects of Drugs AnnualCitation Excerpt :There were adverse effects in 45, which led to drug withdrawal in 24. In a prospective, add-on, open study in 82 patients, aged 3–34 years, with partial (n = 47) or generalized (n = 35) refractory epilepsy, zonisamide was started in a dosage of 1 mg/kg/day and increased by 2 mg/kg every 1–2 weeks over a period of 3 months up to a maximum dose of 12 mg/kg/day [439c]. After 12 months the mean dosage was 5.7 mg/kg/day and nine patients were seizure-free.
Effectiveness and tolerability of zonisamide in children with epilepsy: A retrospective review
2010, SeizureCitation Excerpt :There are no published randomised clinical trials (RCT) of zonisamide use in children. There are several open-label adjunctive or ‘add-on’ studies reporting on children with mostly refractory seizures.10,11,16–21 The responder rates, defined as a reduction in seizure frequency of at least 50%, range from 15% to 48.7%10,16–20 but the time that these responses have been evaluated has not been standardised.
Bioequivalence of Different Formulations of Zonisamide Oral Suspensions: A Short Review
2023, Patient Preference and AdherenceEffectiveness of zonisamide in childhood refractory epilepsy
2022, Child's Nervous SystemLong-term effects of zonisamide in adult patients with intellectual disability
2021, Acta Neurologica Scandinavica