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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The availability of new antiepileptic drugs with different mechanisms of action has widened our therapeutic choice, allowing better tailoring of treatment regimens to address specific needs. Zonisamide is the latest addition to the pharmacological management of epilepsy in Europe, following extensive clinical experience in Japan and the USA. This article reviews the structure, mechanism of action, pharmacokinetics and drug interactions of zonisamide. The four double-blind, placebo-controlled trials in patients with drug-resistant focal seizures are also presented. They complement pre- and postmarketing studies conducted in Japan and provide clear-cut evidence that the drug has efficacy as an add-on treatment in this indication. Reports on zonisamide monotherapy and on the use of the drug for the control of several types of seizures (typical and atypical absences, tonic and myoclonic) and syndromes in children and adults are also commented on. These were all open-label studies, as is often the case with other antiepileptic drugs, dealing with treatment of epilepsy in children. The Japanese, US and European data provide a large database of safety information suggesting that the drug is well tolerated with mild-to-moderate adverse events (e.g., somnolence and dizziness). Nephrolithiasis appears to have a very low incidence and cutaneous reactions are rare. The available data provide an excellent foundation on which clinicians can build their knowledge on this drug, although the broad-spectrum efficacy of zonisamide needs to be confirmed through randomized trials.
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PMID:Zonisamide for the treatment of epilepsy. 1700 16

Zonisamide is an adjuvant for the treatment of patients with partial epilepsy, with or without secondary generalisation. It affects, among other things, the voltage-sensitive sodium and calcium channels, thus disrupting synchronised neuronal firing; as a result, it diminishes the spread of seizure discharges.
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PMID:[New medications; zonisamide]. 1708 49

Anti-epilepsy medications have frequently been used in the treatment of neuropathic pain to reduce the transmission of nociceptive signals.(1,2) Zonisamide is a sulfonamide drug that was approved in 2000 for the adjunctive treatment of partial seizures in adults. Because of the unique combination of mechanisms through which zonisamide functions, it has potential to be a useful option in the treatment of refractory neuropathic pain. We present the case of a patient with refractory neuropathic pain related to idiopathic polyneuropathy, who responded to adjunctive treatment with zonisamide.
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PMID:A possible role for zonisamide in treating neuropathic pain: a case of idiopathic polyneuropathy. 1714 87

Zonisamide safety was evaluated based on a postmarketing surveillance study of patients treated for 1-3 years. Nine hundred twenty-eight children and 584 adult (ages 1 month to 79 years), including 372 newly-diagnosed patients, received zonisamide for partial and generalized epilepsies. Of the intractable patients, 1088 received zonisamide in combination with other antiepileptic drugs (AED), and 52 successfully transitioned to zonisamide monotherapy. A total of 1089 adverse events occurred in 476 (31.5%) of 1512 patients. Incidence of adverse effects was significantly lower among patients receiving zonisamide monotherapy than in those receiving polytherapy: 21% (18.9% of children, 29.4% of adults) versus 35.6% (30.4% of children, 41.7% of adults), respectively. The total incidence of adverse effects was lower for children (26.2%) than for adults (39.9%). Most common adverse events included mental/psychiatric symptoms (19.4%), gastrointestinal symptoms (8.7%), and neurological symptoms (6.5%). Effects that seemed unique to zonisamide were impairment of mental function, motivation or volition, and hipohidrosis. Urinary calculi were detected in only two patients (0.13%). Teratogenicity was evaluated in six patients. Two patients on zonisamide monotherapy and three on polytherapy delivered normal children. One of four patients on polytherapy conceived a fetus with a skull defect with cerebral and cerebellar dysgenesis, namely anencephaly.
Seizure 2007 Jan
PMID:Erratum to "Safety of zonisamide therapy: prospective follow-up survey.". 1551 92

An approach to the selection of appropriate antiepileptic drugs (AEDs) for inclusion in polytherapy is to take into account both the efficacy of a drug and also its mechanism of action and pharmacokinetic profile. The AED zonisamide is licensed in Europe and the USA for use as adjunctive therapy in adult patients with partial onset epilepsy. Four pivotal clinical studies in patients with refractory partial seizures demonstrated that zonisamide as an add-on was most effective at doses of >or=300 mg/day, with responder rates (>or=50% reduction from baseline in seizure frequency) ranging from 28 to 47% for all seizures. In addition, zonisamide has a unique combination of multiple mechanisms of action that are potentially complementary with concomitant AEDs. Zonisamide has no clinically relevant effects on the pharmacokinetics of other commonly used AEDs, however, co-administration with cytochrome P450 3A4 (CYP3A4) inducers or inhibitors may change zonisamide's pharmacokinetic profile. Zonisamide is well tolerated with the majority of adverse events being mild-to-moderate and generally manageable. The tolerability of zonisamide has also been shown to improve with slower drug titration and duration of drug treatment. These characteristics suggest that zonisamide may be suitable as a key adjunct in rational polytherapy.
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PMID:Efficacy and safety of adjunctive zonisamide therapy for refractory partial seizures. 1755 70

(1) The first-line treatment for patients with partial epilepsy is carbamazepine monotherapy. Second-line options include monotherapy with valproic acid, gabapentin, lamotrigine or oxcarbazepine. Other antiepileptics are also available for combination therapy of refractory partial epilepsy. (2) Zonisamide is a sulphonamide derivative that inhibits carbonic anhydrase; it resembles topiramate, a drug already approved for use for this indication in the European Union. (3) The main clinical trial, a double-blind study lasting 36 weeks, compared the addition of zonisamide or placebo to ongoing treatment in 351 patients with refractory partial epilepsy. The "response rate" (the proportion of patients with at least a 50% reduction in the frequency of seizures) was significantly higher with zonisamide plus the previous treatment than with placebo plus the previous treatment (46.6% versus 17.6%). An indirect comparison suggests that this is no better than treatment with a second-line antiepileptic drug. (4) Results of three other placebo-controlled trials of third-line combinations in a total of 499 patients treated for 12 weeks were similar. (5) The main adverse effects of zonisamide are those typically seen with topiramate: neuropsychological disorders and disorders due to carbonic anhydrase inhibition (kidney stones, reduced perspiration, and hyperthermia). There are various other adverse effects, including a risk of severe skin rash. (6) The profile of interactions is complex. There is a risk of pharmacokinetic interactions, and of pharmacodynamic interactions with other carbonic anhydrase inhibitors. (7) In France, treatment with zonisamide costs nearly 20 times more than treatment with carbamazepine or valproic acid. (8) Zonisamide has no therapeutic advantages over other antiepileptics available for combination therapy of partial epilepsy.
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PMID:Zonisamide: new drug. No advantage in refractory partial epilepsy. 1758 22

Antiepileptic drugs (AEDs) suppress seizures by selectively modifying the excitability of neurons and blocking seizure firing with minimal disturbance of nonepileptic activity. All AEDs have been shown to work by at least one of 3 main mechanisms of action: through modulation of voltage-gated ion channels, enhancement of synaptic inhibition, and inhibition of synaptic excitation. Zonisamide is a novel AED that has a broad combination of complementary mechanisms of action, which may offer a clinical advantage over other antiepileptic agents. By altering the fast inactivation threshold of voltage-dependent sodium channels, zonisamide reduces sustained high-frequency repetitive firing of action potentials. Zonisamide also inhibits low-threshold T-type calcium channels in neurons, which may prevent the spread of seizure discharge across cells. In addition, zonisamide is a weak inhibitor of carbonic anhydrase. However, this mechanism is not believed to contribute to the antiepileptic activity of zonisamide. Although zonisamide also seems to alter dopamine, serotonin, and acetylcholine metabolism, it is not clear to what extent these effects on neurotransmitters are involved in the clinical actions of the drug. In addition to these actions, recent evidence suggests that zonisamide may exert neuroprotective actions, independent of its antiepileptic activity. These potential effects may be important in preventing neuronal damage caused by recurrent seizures. Therefore, it seems that the multiple pharmacological actions of zonisamide may contribute to the seizure reductions observed in a wide range of epilepsies and may help to preserve efficacy in individual patients despite possible changes in electrophysiological status.
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PMID:Clinical pharmacology and mechanism of action of zonisamide. 1776 20

Zonisamide is an antiepileptic drug widely used to treat seizures worldwide. In addition to epilepsy, zonisamide may have beneficial efficacy in various neurological or psychiatric diseases. This article reviews the structure, mechanism of action, pharmacokinetics and possible antiparkinsonian action of zonisamide. A multicentered, randomized, double-blind, placebo-controlled study conducted in Japan provided data suggesting that zonisamide, as an add-on treatment, has efficacy in treating motor symptoms in patients with Parkinson's disease (PD). Zonisamide may be effective in reducing the duration of 'off' time in patients with PD treated with L-DOPA. The therapeutic doses of zonisamide for the treatment of PD are 50-100 mg/day, considerably lower than those for the treatment of epilepsy (200-400 mg/day). It is expected that zonisamide will be safe and tolerated in patients with PD, as it has been used as an antiepileptic for more than 15 years; however, further studies are required to evaluate its safety and tolerability in the treatment of PD. The pharmacological mechanisms of the beneficial actions of zonisamide in PD remain unclear. Various hypotheses have been proposed, but the supporting data are not yet sufficient to draw any conclusions. Further basic research is required to advance our understanding of the antiparkinsonian mechanism of zonisamide.
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PMID:Zonisamide for the treatment of Parkinson's disease. 1786 6

Zonisamide is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. Preclinical studies have reported a range of potential mechanisms of action for zonisamide, such as blocking voltage-gated sodium channels, reduction of T-type calcium channel currents, and enhancement of gamma-aminobutyric acid (GABA)-mediated inhibition, which are indicative of its broad antiseizure effects. Zonisamide has a favorable linear pharmacokinetic profile, a long half-life, and a low incidence of protein-binding interactions with other AEDs. Hepatically metabolized through the cytochrome P450 pathway, zonisamide does not induce its own metabolism or liver enzymes. For more than 2 decades, zonisamide has been extensively used as monotherapy and adjunctive therapy for the treatment of partial and generalized seizures in pediatric and adult patients in Japan. Zonisamide was approved in the USA in 2000 as adjunctive therapy for partial seizures in adults. With over 2 million patient-years of exposure internationally, zonisamide has demonstrated safety and efficacy against a multitude of epilepsy and seizure types, including both partial and generalized seizures. This review focuses on the experience and use of zonisamide in partial seizures, as well as possible new uses for zonisamide.
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PMID:Zonisamide - a review of experience and use in partial seizures. 1941 74

Zonisamide (ZNS) efficacy and safety in epilepsy have been demonstrated in four double-blind, placebo-controlled studies. In the present article, we examined all long-term studies performed with this drug. Nine open-label studies, in which ZNS had been administered as an add-on or as monotherapy to epileptic patients for at least 6 months, were selected for our analysis. Four outcome measures were searched. Retention of this drug after 1 year varied between 45% and 65%. The percentages of patients achieving a >/=50% seizure reduction, with respect to baseline, ranged between 37% and 65%. In patients with drug-resistant forms of epilepsy, the percentage of patients reaching a 6-month seizure freedom period was 9%. The percentages of patients who discontinued the experimental drug due to adverse effects ranged between 4% and 24%. Somnolence and dizziness were the most frequently reported adverse effects. Long-term studies demonstrate that ZNS has a good efficacy and tolerability profile, and support its use as adjunctive therapy for epileptic patients.
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PMID:Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. 1955 19


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