Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0238111 (Lennox-Gastaut syndrome)
 861 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zonisamide is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug. It has shown activity in various animal models of epilepsy, and although a detailed mode of action awaits clarification it appears to block the propagation/spread of seizure discharges and to suppress the epileptogenic focus. Clinical experience with zonisamide in Japan has documented its efficacy in the treatment of partial seizures (partial-onset generalised tonic-clonic, simple partial and/or complex partial seizures), and to a more variable extent, generalised tonic-clonic, generalised tonic (mainly seen in symptomatic generalised epilepsies including Lennox-Gastaut Syndrome) and compound/combination seizures (including those refractory to treatment with other antiepileptic drugs). Other generalised seizure types have also responded to therapy with zonisamide, although only small patient numbers were studied. Zonisamide has demonstrated efficacy equivalent to that of carbamazepine in patients with (mainly) partial seizures, and to that of valproic acid in a small study of children (n = 32) with generalised seizures. Animal studies suggest that zonisamide possesses a more favourable therapeutic index than most other antiepileptic drugs. However, clinical trials conducted to date, have not confirmed any overt tolerability advantage. Indeed, whereas the recommended therapeutic plasma zonisamide concentration is 20 mg/L, clinical investigations have associated adverse events with plasma zonisamide concentrations of > 30 mg/L, suggesting the usefulness of therapeutic drug monitoring. Moreover, although plasma concentrations of zonisamide are empirically regarded to be proportional to therapeutic doses in patients in Japan, nonlinear pharmacokinetics have been reported for this drug in patients in the US and may further complicate its use in this patient population. Additional pharmacokinetic studies will help to establish the change in pharmacokinetic profile that occurs with dosage titration in patients outside Japan. Among 700 patients treated with zonisamide in Europe/US, a high incidence of renal calculi (1.9%) has been noted, however, the causal relationship to zonisamide is disputed. Indeed, although urinary lithiasis has also been recorded for patients in Japan, the aetiology, incidence and spontaneous regression of this condition suggest that it is not a serious problem for this patient population. Until this difference is clarified, it is likely that zonisamide will find its greatest use in the treatment of patients in Japan. Like many other established antiepileptic drugs, available data suggest the propensity for zonisamide to alter the pharmacokinetic profile of other anticonvulsant agents, although severe interactions appear to be unlikely.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. 768 68

A brief review of epilepsy as a disease, anti-epileptic drugs and methods of evaluation of anti-epileptic drugs are presented as a background for assessment of zonisamide, which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. Chemically, zonisamide is classified as a sulphonamide and is unrelated to other anti-epileptic drugs. The mode of action of zonisamide remains unclear, but likely mechanisms are blockade of sodium and T-type calcium channels. It is also shown to have some neuroprotective effect against hypoxia and ischaemia. It has a liner pharmacokinetics with excellent oral bioavailability. Zonisamide has been approved for use in Japan for ten years prior to approval in USA and Europe. Clinical experience with zonisamide in Japan has documented its efficacy in the treatment of partial seizures (partial-onset generalised tonic-clonic, simple partial and/or complex partial seizures) and to a more variable extent, generalised tonic-clonic, generalised tonic (mainly seen in symptomatic generalised epilepsies including Lennox-Gastaut Syndrome) and compound/combination seizures. The efficacy and safety was confirmed in trials conducted in USA and Europe in adults as well as children. Zonisamide compares favourably with other newly introduced drugs and has the potential for development as a monotherapy for epilepsy.
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PMID:An assessment of zonisamide as an anti-epileptic drug. 1124 91

Zonisamide is a novel anticonvulsant that is structurally and mechanistically unique, compared with other antiepilepsy drugs. Available in Japan and South Korea since 1989, it was approved in the United States in the year 2000 as adjunctive therapy for partial seizures in adults. There has been extensive clinical trial and clinical practice experience with zonisamide therapy in Japanese children. Open-label data from pediatric clinical trials conducted in Japan suggest that zonisamide is well tolerated and effective against partial- and generalized-onset seizures in children. Despite this wealth of open-label data, no formal pharmacokinetic studies and only one well-controlled trial of zonisamide's efficacy and safety in Japanese children have been completed to date. No controlled clinical trials of zonisamide in children have been completed in the United States or Europe. Additional controlled trials in children with partial- or generalized-onset seizures, infantile spasms, and Lennox-Gastaut syndrome are warranted to further delineate zonisamide's broad spectrum of efficacy and tolerability in children.
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PMID:Zonisamide in pediatric epilepsy: review of the Japanese experience. 1195 83

Epilepsy is a common comorbidity among developmentally disabled (DD) patients, and special considerations apply to its treatment. In particular, clinicians should try to avoid antiepileptic drugs (AEDs) with sedating properties or adverse cognitive effects that might further diminish quality of life for DD patients. Behavioral changes due to medication and significant pharmacokinetic interactions with other medications are also concerns. The newer AEDs, approved in the 1990s, offer new options for the treatment of individuals with developmental disability and epilepsy. Gabapentin does not interact with the hepatic metabolism of other AEDs or psychotropic agents, results in a statistically significant reduction in seizure frequency in mentally retarded children, and is generally well tolerated. Felbamate is an effective broad-spectrum AED, but has serious toxicity issues limiting its use. Lamotrigine has been extensively studied in the DD population, achieving seizure reduction rates of up to 50% in some trials. Although it is usually well tolerated in this population, its pharmacokinetic profile is influenced by concomitant medications. Levetiracetam has been found to be effective against kindled seizures and has been approved as adjunctive therapy for partial epilepsies. It does not cause any pharmacokinetic interactions, but may have behavioral side effects. Oxcarbazepine is a homologue of carbamazepine that has fewer drug interactions. It is approved for mono- or adjunctive therapy in patients with partial seizures, and its use in DD individuals appears to be worthwhile. Tiagabine is extensively bound to plasma proteins and is therefore subject to protein-binding displacement interactions by other highly protein-bound drugs, such as sodium valproate. While there are trial data showing its efficacy as adjunctive therapy in partial epilepsy in adults and children, there is a paucity of data specific to the DD population. Common side effects include sedation. Topiramate is a broad-spectrum AED approved as adjunctive therapy for partial and primary generalized tonic-clonic seizures. It appears to be particularly effective in patients with Lennox-Gastaut syndrome and those with cognitive disabilities. It appears to be better tolerated in the DD population than in the general population. Zonisamide has been effective in the DD population, yielding a seizure reduction of 50% in 41% of children in 1 trial. It has been associated with renal stone formation, sedation, and cognitive effects, however. The new AEDs have a role in treating seizures in the DD. Side effects that limit their use include anorexia, behavioral changes, and sedation. Seizure exacerbation can occur with the new AEDs and success is defined empirically and by improvements in quality of life.
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PMID:Antiepileptic drug treatment in the developmentally disabled: treatment considerations with the newer antiepileptic drugs. 1260 9

Treatment of the catastrophic epilepsies [infantile spasms (IS), Lennox-Gastaut syndrome (LGS), and progressive myoclonic epilepsy (PME)] remains a challenge to clinicians. For IS, adrenocorticotropic hormone has traditionally been the drug of choice in the United States but may be associated with serious side effects in some patients. Vigabatrin has shown promise in treating IS patients, particularly those with tuberous sclerosis. However, the drug is associated with visual field loss and is not commercially available in the United States. Newer antiepilepsy drugs (AEDs), such as zonisamide, topiramate (TPM), and lamotrigine (LTG), may be useful in patients with IS. Although LTG, TPM, and felbamate are approved in the United States for the treatment of LGS, the overall effectiveness of therapy in patients with LGS is poor. For PME, valproate is a first-line treatment. Zonisamide and levetiracetam also show promise. Supplementation with certain cofactors to correct deficiencies and increase mitochondrial function may be useful in some patients with PME, but response to such therapy is not well documented. Advances in our understanding of the etiologies, mechanisms, and genetics underlying the catastrophic epilepsies may facilitate more effective pharmacologic interventions.
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PMID:Pharmacologic treatment of the catastrophic epilepsies. 1528 6

Zonisamide is a new type of benzisoxazole derivative, first marketed in Japan in 1989. This study analyzed: (1) the drug's efficacy by seizure and epilepsy type in a total of 1008 patients treated during the development of zonisamide in Japan; (2) the effectiveness of zonisamide for 726 newly-diagnosed patients treated with zonisamide postmarketing; and (3) 50 patients with generalized epilepsies and epileptic syndromes (idiopathic generalized epilepsies, symptomatic generalized epilepsies, Lennox-Gastaut syndrome, Doose syndrome, and West syndrome), and 19 patients with undetermined epilepsies and specific syndromes (refractory grand mal in childhood, severe myoclonic epilepsy in infancy, other undetermined epilepsy, familial essential myoclonic epilepsy, and mitochondrial encephalomyopathy with ragged-red fibers). Analysis of study results showed that among all patients treated, zonisamide was highly effective for the treatment of idiopathic generalized epilepsy, temporal lobe epilepsy, and other partial epilepsies. The compound was also effective for other symptomatic generalized epilepsies. In 50 patients with generalized epilepsies, and 19 with undetermined epilepsies and specific syndromes, seizure frequency was reduced by >50% with monotherapy or two-drug therapy with zonisamide. Zonisamide was effective not only for partial epilepsies and generalized epilepsies but also for undetermined epilepsies and specific syndromes such as myoclonus epilepsy.
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PMID:Overview of Japanese experience-controlled and uncontrolled trials. 1551 80

The current overview of zonisamide use and effectiveness is based on both a long-term prospective postmarketing survey and current zonisamide use at the Saitama Medical College, Department of Neuropsychiatry. Survey data, which were collected from individual physicians and 23 survey groups throughout Japan, assessed the effectiveness of zonisamide in 1631 patients. Zonisamide was highly effective for treating partial seizures, with 70% of patients reporting improvement. More than half of patients with generalized seizures (58%) and half of patients with myoclonic and atypical absence seizures showed improvement with zonisamide treatment. Among the different epileptic syndromes, zonisamide was highly effective in treating generalized idiopathic epilepsy (> or =78% improvement) and partial epilepsy (> or =58% improvement). However, only 28% of patients with West syndrome or Lennox-Gastaut syndrome showed improvement. Among 60 outpatients treated with zonisamide at our facility as of October 1998, most had partial seizures or generalized seizures subsequent to partial seizures. The majority of patients received zonisamide in combination with other antiepilepsy drugs. Patients receiving zonisamide monotherapy showed greater improvement than did patients receiving polytherapy. We conclude that zonisamide is highly effective for partial seizures and generalized seizures, and that there appears to be no decrease in efficacy with long-term use.
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PMID:Efficacy of zonisamide: our experience. 1551 89

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved in Europe for the adjunctive treatment of refractory partial seizures in adults, has undergone extensive evaluation in pre- and post-marketing double-blind and open-label studies in Japan (where zonisamide is used widely to treat partial and generalised seizures in adults and children). These data indicate that the clinical benefit of zonisamide extends across a range of seizure types and patient ages. In an analysis based on a mixture of controlled and open studies in adults and children with partial seizures, 51-57% responded to zonisamide treatment (achieving >or=50% reduction in baseline seizure frequency). Efficacy extends across a range of generalised seizures and 22-66% of adults and children experiencing tonic-clonic, tonic, clonic, myoclonic or absence seizures responded to treatment. Even greater responder rates have been reported when zonisamide was used as monotherapy for partial seizures and generalised seizures in patients refractory to other AEDs or with newly diagnosed epilepsy. Zonisamide is also efficacious in paediatric epilepsy syndromes, including Lennox-Gastaut Syndrome, West Syndrome and Ohtahara Syndrome. Across the spectrum of epilepsy syndromes studied, zonisamide is well-tolerated with a low incidence of adverse events, which are generally mild and CNS-related. These data indicate that zonisamide represents a valuable broad-spectrum option for the treatment of epilepsy.
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PMID:Zonisamide in the management of epilepsy--Japanese experience. 1632 7

Zonisamide is an antiepileptic drug used as adjunctive therapy for refractory partial seizures in adults. Because of the multiple mechanisms of action, it shows a broad spectrum of anticonvulsant activity and has been effective in several types of seizures, including partial and generalized seizures, tonic-clonic seizures and absence seizures in patients unresponsive to other anticonvulsants. Myoclonic epilepsy, Lennox-Gastaut syndrome and infantile spasms have also been treated effectively with zonisamide. Recent clinical studies have demonstrated additional potential for therapeutic use in neuropathic pain, bipolar disorder, migraine, obesity, eating disorders and Parkinson's disease. Despite adverse events, zonisamide is relatively safe and well tolerated in patients, and shows low discontinuation rate. It has a good pharmacokinetic profile and a low drug interaction potential. Zonisamide is considered as a drug that effectively reduces the frequency of partial seizures.
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PMID:Zonisamide: review of its use in epilepsy therapy. 1634 Dec 90