Zonisamide for absence seizures

doi:10.1016/j.eplepsyres.2005.02.006

Epilepsy Research

Volume 64, Issues 1–2, March–April 2005, Pages 31-34

https://doi.org/10.1016/j.eplepsyres.2005.02.006 Get rights and content

Abstract

This chart review investigated the efficacy and safety of zonisamide in 45 patients aged ≤18 years with absence seizures. Of these patients, 23 (51.1%) achieved freedom from absence seizures. Two patients discontinued zonisamide, 1 for increased seizures and 1 for sleepiness and inefficacy. These data support the efficacy of zonisamide in treating 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.

Section snippets

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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Cited by (56)

Care of pharmaco-resistant absence seizures in childhood
2024, Revue Neurologique
In childhood absence epilepsy, pharmaco-resistance occurs in 20–30% of patients. In that situation, glucose transporter type 1 deficiency has to be ruled out, especially if absences started before the age of four years and if neurological signs are present. If ethosuximide, valproate and lamotrigine have failed in monotherapy or in association, there are currently no valuable therapeutic options. The same rules apply for epilepsy with myoclonic absences. Importantly, arguments supporting that making the patient seizure-free will improve eventual associated cognitive deficits such as attention deficit are very weak. Therefore, limiting the cognitive side effects of the anti-epileptic drugs has always to be a priority when faced with typical refractory absences in childhood. In epilepsy with eyelid myoclonia, the majority of patients are pharmaco-resistant. However, absence seizures, if present, tend to be very brief, and seizures are limited in many patients to eyelid myoclonia that eventually do not affect their quality of life and are well attenuated by wearing blue lenses. Atypical absences occurring in the course a developmental and/or epileptic encephalopathy are often pharmaco-resistant. In that situation, characterizing the type of epilepsy syndrome and searching for a specific genetic or structural etiology are needed to offer the best therapeutic options to the patient.
Childhood absence epilepsy: An update
2016, Archives de Pediatrie
L’épilepsie absence de l’enfant (EAE) fait partie des syndromes épileptiques les plus fréquents, représentant 10 % des épilepsies pédiatriques. Cette mise au point a pour objectif de rappeler les données les plus récentes et de fournir aux pédiatres les éléments pour la prise en charge initiale. Cette prise en charge initiale est parfaitement envisageable en cabinet. Les patients concernés ont un seul type de crises au moment du diagnostic : crises absences typiques. Les données de l’examen clinique associées à l’enregistrement électro-encéphalographique permettent le diagnostic. Les mécanismes conduisant à cette épilepsie ne sont pas encore identifiés. La majorité des patients entre en rémission, c’est pourquoi on parle d’épilepsie « auto-limitée ». Le terme d’épilepsie « bénigne » n’est plus utilisé car une faible proportion de patients (5–10 %) a une forme résistante et un trouble attentionnel est observé chez presque un tiers des patients. Les enfants atteints ont aussi un risque de difficultés scolaires, souvent en lien avec des troubles spécifiques des fonctions cognitives qui doivent être dépistés afin de prévenir l’échec scolaire et un moins bon devenir psychosocial. Sur le plan thérapeutique, un essai randomisé s’est avéré en faveur d’une utilisation de l’éthosuximide en première intention et du valproate en seconde intention. Les effets secondaires cognitifs doivent être pris en compte tant dans le choix du traitement que dans le suivi. Nous proposons enfin des critères justifiant l’orientation de l’enfant vers un spécialiste.
Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome accounting for 10% of all pediatric epilepsies. The aim of this review is to provide an updated overview of this epilepsy syndrome to pediatricians. Most of the patients can be initially managed in private practice or in general pediatric settings. Absence seizures are the only seizure type observed at the time of diagnosis in these patients. An electroencephalogram recording and a clinical evaluation lead to the diagnosis. The underlying mechanisms are not yet fully understood. CAE is considered a self-limited epilepsy syndrome since most of the patients will become seizure free. Only a few patients (5–10%) have resistant CAE. However, CAE, as well as any pediatric epilepsy syndrome, should not be considered a “benign” epilepsy. Attention deficit is observed in about one third of the patients. There is also an increased risk of academic difficulties related to specific cognitive disorders. Therefore, the early detection of children at risk of developing neuropsychological problems can be helpful for preventing school underachievement and poor psychosocial outcome. Recently, several studies including a large randomized controlled trial indicated that ethosuximide should be considered as a first-line treatment and valproate as a second-line treatment. Cognitive side effects should be an important factor in the selection of the antiepileptic drug and should be specifically assessed during the follow-up. This review concludes by discussing the criteria that might lead to referring the patient to a specialist.
Zonisamide for refractory juvenile absence epilepsy
2014, Epilepsy Research
Citation Excerpt :
All patients were responders, including more than 1/3 seizure free and 23% with at least 75% absence seizure reduction from baseline. The mean dosage of ZNS was 388 mg/day which is in agreement with the therapeutic dosage reported in other studies (Wilfong and Schultz, 2005; Ohtahara, 2006). Four of our patients reached seizure reduction on 550–600 mg/day ZNS, which is higher than the recommended dose of 500 mg/day.
To examine the clinical effect of zonisamide (ZNS) in patients with drug-resistant juvenile absence epilepsy (JAE).
Between 2006 and 2010, 13 JAE patients were successively treated with add-on ZNS. Safety and efficacy were assessed according to the patient and caregiver reports at visits every 3 months. Response rate was defined as a 50% or greater reduction in seizure frequency.
Mean age was 42 years. No patient had been seizure free for a period ≥12 months before ZNS. The mean follow-up was 34 months. The mean dosage of ZNS was 388 mg. ZNS was effective for absence seizures (AS) in all patients (more than 50% AS reduction). Four patients reached seizure reduction on 550–600 mg/day. Three (23%) had a reduction in AS frequency >75% and five (38.5%) between 50% and 75%. Seizure freedom was achieved in five patients (38.5%) (three patients with AS only and two with AS plus generalized tonic-clonic seizures (GTCS)). Before ZNS, four patients had AS evolving to absence status. After ZNS, three of them were in the seizure-free group, the later never experienced this type of complication. Among seven patients with AS plus GTCS, two of them did not report any improvement in the frequency of GTCS (29%).
This observational post-marketing study confirms the broad-spectrum activity of ZNS that includes GTCS, myoclonic seizures and now AS. This study provides evidence that add-on ZNS is efficient and well tolerated in adult patients with refractory JAE, even at high doses.
Current advances in childhood absence epilepsy
2014, Pediatric Neurology
Childhood absence epilepsy is an age-dependent, idiopathic, generalized epilepsy with a characteristic seizure appearance. The disorder is likely to be multifactorial, resulting from interactions between genetic and acquired factors, but the debate is still open. We review recent studies on different aspects of childhood absence epilepsy and also to describe new concepts.
Data for this review were identified using Medline and PubMed survey to locate studies dealing with childhood absence epilepsy. Searches included articles published between 1924 and 2013.
The diagnosis comprises predominant and associated seizure types associated with other clinical and electroencephalographic characteristics. Many studies have challenged the prevailing concepts, particularly with respect to the pathophysiological mechanisms underlying the electroencephalographic seizure discharges. Childhood absence epilepsy fits the definition of system epilepsy as a condition resulting from the persisting susceptibility of the thalamocortical system as a whole to generate seizures. This syndrome, if properly defined using strict diagnostic criteria, has a good prognosis. In some cases, it may affect multiple cognitive functions determining risk for academic and functional difficulties; the detection of children at risk allows tailored interventions. Childhood absence epilepsy is usually treated with ethosuximide, valproate, lamotrigine, or levetiracetam, but the most efficacious and tolerable initial empirical treatment has not been well defined.
We review recent studies and new concepts on the electroclinical features and pathophysiological findings of childhood absence epilepsy in order to highlight areas of consensus as well as areas of uncertainty that indicate directions for future research.
Antiepileptic drugs. Advantages and disadvantages
2012, Handbook of Clinical Neurology
Citation 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.
Antiepileptic drug (AED) monotherapy is the first-line treatment of epilepsy. AED therapy is effective in controlling seizures in approximately two-thirds of patients with epilepsy, but AEDs only suppress seizures and there is no evidence that current commercially available AEDs modify the natural course of epilepsy. Individual AEDs may have relative advantages and disadvantages depending on seizure type, specific epilepsy condition, age group, comorbidity, interactions, and a variety of individual factors. Some AEDs have demonstrated efficacy as initial monotherapy and others have only been studied as adjunctive therapy. AED efficacy is often difficult to predict. Drug resistance is encountered in approximately one-third of patients with epilepsy; even seizure aggravation may occur, particularly for certain AEDs in generalized epilepsy syndromes. Tolerance, the loss of efficacy over time, is most often seen with benzodiazepines, but may also occur with other AEDs. AED use may also be limited by toxicity, including dose-related, idiosyncratic, acute, and chronic adverse effects, all of which vary remarkably across individual AEDs and individual patients. The practitioner must consider AED advantages and disadvantages for every patient. When seizure freedom cannot be achieved with AED therapy without unacceptable adverse effects, nonpharmacological therapy including epilepsy surgery may need to be considered.
Comparative trial of low- and high-dose zonisamide as monotherapy for childhood epilepsy
2011, Seizure
To evaluate the effectiveness of zonisamide (ZNS) as monotherapy in children with newly diagnosed epilepsy.
This randomized, multicenter trial included a 2–4-week titration and a 24-week maintenance phase after randomization to low-(3–4 mg/kg/day) or high-(6–8 mg/kg/day) dose groups as target maintenance dosages. The primary outcome measure was the seizure-free rate over 6 months, while a secondary measure was the change in cognition and behavior from screening to the end of the maintenance phase.
Out of 125 patients enrolled, 90 (49 low-dose and 41 high-dose) completed the study. Forty-one patients (63.1%) in the low-dose group and 34(57.6%) in the high-dose group achieved 6 months’ freedom from seizures (p = 0.66). After treatment, the picture arrangement subtest improved in the low-dose group (p = 0.047) while the vocabulary subtest worsened in the high-dose group (p = 0.020). Comparing between the two groups, the vocabulary subtest in the high-dose group was significantly worse than that in the low-dose group (p = 0.002). Social competence, somatic complaints, depression/anxiety and delinquent and aggressive behavior in the low-dose group were significantly improved (p < 0.05). Moreover, total social competence, somatic complaints, delinquent behavior, externalizing, and total behavior problems were significantly more improved in the low-dose group than the high-dose group (p < 0.05).
ZNS is an effective monotherapy for newly diagnosed childhood epilepsy. Lower doses of ZNS have a similar efficacy and more beneficial neurocognitive effects compared to higher doses. When prescribing higher doses of ZNS, one must be aware of the possible manifestation of problems associated with language development, such as those affecting vocabulary acquisition.

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Zonisamide for absence seizures

Abstract

Introduction

Section snippets

Methods

Demographic and treatment characteristics

Discussion

Acknowledgments

Brain Dev

Neuron

Epilepsy Res.

Epilepsy Res.

Zonisamide as adjunctive and monotherapy in absence epilepsy [abstract]

Epilepsia