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      Profile of once-daily zonisamide as monotherapy for treatment of partial seizures in adults

      Drug Design, Development and Therapy

      Dove Medical Press

      epilepsy, zonisamide, monotherapy

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          Abstract

          Epilepsy is one of the most common neurologic disorders, affecting about 50 million people around the world. It is recognized that around 50% of patients with newly diagnosed epilepsy become seizure-free with the first drug treatment, so the choice of first antiepileptic drug is crucial. This paper provides a comprehensive overview of zonisamide as monotherapy for partial seizures, with special attention to the possibility of a once-daily regimen. The available data suggest that zonisamide is an effective and well tolerated option as monotherapy. Once-daily dosing is indicated, considering the long plasma half-life and linear pharmacokinetics of the drug. Zonisamide 300 mg was shown to be noninferior to carbamazepine 600 mg in terms of efficacy and safety, but even lower doses may be effective. Finally, the broad spectrum of efficacy in different seizure types, the low drug interaction potential, and the possibility of weight loss make zonisamide a preferred option in many epilepsy practices. Further data on monotherapy, especially in special populations, such as women of childbearing potential, are needed.

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          Most cited references 42

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          A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology.

           Jerome Engel (2001)
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            Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy.

            We report the results of a prospective study of the efficacy and tolerability of levetiracetam, a new antiepileptic drug with a unique mechanism of action, in comparison with controlled-release carbamazepine as first treatment in newly diagnosed epilepsy. Adults with > or =2 partial or generalized tonic-clonic seizures in the previous year were randomly assigned to levetiracetam (500 mg twice daily, n = 288) or controlled-release carbamazepine (200 mg twice daily, n = 291) in a multicenter, double-blind, noninferiority, parallel-group trial. If a seizure occurred within 26 weeks of stabilization, dosage was increased incrementally to a maximum of levetiracetam 1,500 mg twice daily or carbamazepine 600 mg twice daily. Patients achieving the primary endpoint (6-month seizure freedom) continued on treatment for a further 6-month maintenance period. At per-protocol analysis, 73.0% (56.6%) of patients randomized to levetiracetam and 72.8% (58.5%) receiving controlled-release carbamazepine were seizure free at the last evaluated dose (adjusted absolute difference 0.2%, 95% CI -7.8% to 8.2%) for > or =6 months (1 year). Of all patients achieving 6-month (1-year) remission, 80.1% (86.0%) in the levetiracetam group and 85.4% (89.3%) in the carbamazepine group did so at the lowest dose level. Withdrawal rates for adverse events were 14.4% with levetiracetam and 19.2% with carbamazepine. Levetiracetam and controlled-release carbamazepine produced equivalent seizure freedom rates in newly diagnosed epilepsy at optimal dosing in a setting mimicking clinical practice. This trial has confirmed in a randomized, double-blind setting previously uncontrolled observations that most people with epilepsy will respond to their first-ever antiepileptic drug at low dosage.
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              The natural history of epilepsy: an epidemiological view.

              Better information of the natural history of epilepsy has important implications for understanding the underlying neurobiology, evaluating treatment strategies, and planning healthcare resources. The traditional pessimistic view has been dispelled by results from modern community based prospective studies, showing that over 60% of newly diagnosed patients will enter remission upon treatment. Recent outcome studies suggest that medical intractability may be predicted after failure of two antiepileptic drugs. Poor prognostic factors include a high initial seizure density, symptomatic aetiology, and presence of structural cerebral abnormalities, all of which can be identified early on. Among patients who have entered remission, many will remain seizure-free after antiepileptic drug treatment is withdrawn, suggesting that the underlying seizure generating factor has remitted. Whether some of these patients have entered remission "spontaneously" is contentious because, with effective pharmacotherapy for epilepsy in use for over 100 years, the natural history of untreated epilepsy is largely unknown. Circumstantial evidence, mostly arising from resource poor countries where antiepileptic drug treatment is not readily available, indicates that spontaneous remission may occur in up to 30% of cases. Observations from these complementary sources suggest that, at the population level, prognosis of newly diagnosed epilepsy may be broadly categorised into three groups: remission without treatment, remission with treatment only, and persistent seizures despite treatment. As understanding of the prognostic factors improves, the potential of a "prognostic group specific" management approach should be explored so that effective treatments may be used in a more rational and targeted fashion.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2013
                14 May 2013
                : 7
                : 397-402
                Affiliations
                Division of Neurology, Trinity Hospital, Borgomanero, Italy
                Author notes
                Correspondence: Marco Mula, Division of Neurology, Trinity Hospital, Viale Zoppis 10, Borgomanero 28021, Italy, Tel +39 0322 848 581, Email marcomula@ 123456yahoo.it
                Article
                dddt-7-397
                10.2147/DDDT.S43612
                3660130
                23700365
                © 2013 Mula, publisher and licensee Dove Medical Press Ltd

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Categories
                Review

                Pharmacology & Pharmaceutical medicine

                monotherapy, zonisamide, epilepsy

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