Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial

Schmidt, Dieter; Jacob, Robin; Loiseau, P; Deisenhammer, E; Klinger, Donna L.; Despland, A.; Egli, Mathias; Bauer, Gerhard; Stenzel, Elena; Blankenhorn, V.

doi:10.1016/0920-1211(93)90011-u

Cited by 220 publications

(146 citation statements)

References 13 publications

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“…In the 12-week observation period, the final median seizure change was a 27.7% reduction in the ZNS group and a 3.9% increase in the placebo group (p = 0.01). In the ZNS group, 30.3% had a 50% or larger decrease compared to 12.7% in the placebo group (p < 0.02) (40).…”

Section: Efficacy In Localization-related Epilepsiesmentioning

confidence: 99%

“…In the European multicenter, double-blind, placebocontrolled study, 139 adult patients with four or more complex partial seizures per month were randomized to ZNS (n = 71) or placebo (n = 68) (40). The median daily dose in ZNS responders was 7.8 mgkg with blood levels of 17.0 Fg/ml and 6.8 mg/kg with blood levels of 15.2 pg/ml in nonresponders.…”

Section: Efficacy In Localization-related Epilepsiesmentioning

confidence: 99%

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Zonisamide

Leppik

1999

Epilepsia

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Summary: Zonisamide (ZNS) is a broad-spectrum antiepileptic drug in both animal models of epilepsy and patients with epilepsy. It is effective for both localization-related and generalized epilepsies and appears to be particularly potent in progressive myoclonic epilepsy syndromes. Its pharmokinetic profile is favorable, with a long half-life and low protein binding.However, its insolubility may make the development of a parenteral formulation difficult. Its safety profile is good, although teratogenicity in animal models is of concern. Adult doses of 400-600 mg per day in two doses, with blood levels from 20 to 30 mg/ml, appear to be effective.

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Section: Efficacy In Localization-related Epilepsiesmentioning

confidence: 99%

Section: Efficacy In Localization-related Epilepsiesmentioning

confidence: 99%

Zonisamide

Leppik

1999

Epilepsia

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“…Two class I placebo-controlled studies [Faught et al 2001;Schmidt et al 1993] which compared zonisamide (at doses of 20 mg/kg in the Schmidt and colleagues study, and doses of 100, 200, and 400 mg/day in the study by Faught and colleagues) with placebo were reviewed. The discontinuation rates were 10% for both placebo and zonisamide-treated patients.…”

Section: Zonisamidementioning

confidence: 99%

New generation antiepileptic drugs: what do they offer in terms of improved tolerability and safety?

French

Gazzola

2011

Therapeutic Advances in Drug Safety

113

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Over the last two decades a total of 11 antiepileptic drugs (AEDs) have been introduced to the US market. Randomized, placebo-controlled trials have yielded information about each drug's efficacy, tolerability, and safety profile; however, few studies have compared the newer generation AEDs directly with the older generation. Comparative studies are not always straightforward in their interpretation, as many characteristics of drugs, both favorable and unfavorable, may not be highlighted by such studies. In general, findings from the literature suggest that the newer generation AEDs (including vigabatrin, felbamate, gabapentin, lamotrigine, tiagabine, topiramate, levetiracetam, oxcarbazepine, zonisamide, pregabalin, rufinamide, and lacosamide) enjoy both improved tolerability and safety compared with older agents such as phenobarbital, phenytoin, carbamazepine, and valproate. This is partially supported by some of the findings of the QSS and the TTA Committee of the American Academy of Neurology (AAN), whose review of four AEDs (gabapentin, lamotrigine, topiramate, and tiagabine) is discussed. Briefly, when compared with carbamazepine, lamotrigine was better tolerated; topiramate adverse events (AEs) were fairly comparable to carbamazepine and valproate; and tiagabine compared with placebo was associated with a higher discontinuation rate due to AEs. The findings of the SANAD trial are also presented; when administered to patients with partial epilepsy, carbamazepine was most likely to fail due to AEs, and lamotrigine and gabapentin were least likely to fail due to AEs. When administered to patients with idiopathic generalized epilepsy, topiramate was most frequently associated with AE-related discontinuation, followed by valproate; and while valproate was the most efficacious drug in this arm of the study, lamotrigine was more tolerable. What makes the SANAD study valuable and somewhat unique is its head-to-head comparison of one drug with another. Such comparative trials are overall lacking for new AEDs, although some conclusions can be drawn from the available data. In the end, however, AED selection must be based on individual patient and drug characteristics.

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“…Zonisamide was developed as an anticonvulsant and has been applied in the treatment of tonic-clonic convulsion and psychomotor seizure (1,2). Proposed mechanisms for its antiepileptic activity include alteration of the fast inactivation threshold of voltage-dependent sodium channels, resulting in sustained reduction of high-frequency repetitive firing of action potentials, and inhibition of low-threshold T-type calcium channels in neurons, which may prevent the spread of seizure discharge across cells (3 -5).…”

Section: Introductionmentioning

confidence: 99%

Zonisamide Increases Dopamine Turnover in the Striatum of Mice and Common Marmosets Treated With MPTP

et al. 2009

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Abstract. The effect of zonisamide, an antiepileptic agent with anti-parkinsonian effects, was studied on dopamine neurons of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 mice and common marmosets. Groups of mice (n = 8 -9) were treated with: MPTP (15 mg/ kg every 2 h ×4); MPTP plus zonisamide (40 mg/kg administered 1 h before each MPTP dose); MPTP plus selegiline (2 mg/kg administered 1 h before the first MPTP dose); zonisamide (40 mg/ kg ×4); and saline controls. Groups of common marmosets (n = 4 -6) were treated with: MPTP (2.5 mg/kg every 24 h ×3); MPTP plus zonisamide (40 mg/kg administered 1 h before each MPTP dose); MPTP plus selegiline (2 mg/ kg administered 1 h before the first MPTP dose); and saline controls. Brain dopamine and its metabolites were determined by HPLC. Dopamine content decreased in the striatum of MPTP-treated mice and monkeys. Co-administration of selegiline inhibited the effect of MPTP and dopamine contents were similar to those of the controls. Co-administration of zonisamide did not inhibit the effect of MPTP on dopamine content, but increased striatal dopamine turnover of animals treated with MPTP plus zonisamide more than in those treated with MPTP alone. MPTP treatment caused a compensatory increase of dopamine turnover in the striatum by remaining neurons. Zonisamide may help dopaminergic neurons by increasing striatal dopamine turnover following MPTP treatment.

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Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial

Cited by 220 publications

References 13 publications

Zonisamide

Zonisamide

New generation antiepileptic drugs: what do they offer in terms of improved tolerability and safety?

Zonisamide Increases Dopamine Turnover in the Striatum of Mice and Common Marmosets Treated With MPTP

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