Abstract
Background and Objective: Clinical studies have reported that zonisamide is effective for a wide range of seizure types, including refractory partial-onset seizures. However, there have been no reported studies of the efficacy of zonisamide in the Chinese population to date. The aim of the present study was to evaluate the efficacy and safety of zonisamide in the treatment of adult Chinese patients with refractory partial-onset epilepsy.
Methods: This was a randomized, double-blind, placebo-controlled trial conducted over a 16-week period. 104 patients with refractory partial-onset epilepsy were enrolled. Participants were randomly assigned to receive addon zonisamide or placebo. Zonisamide was titrated to a target dosage of 300 or 400 mg/day. Seizure frequency and adverse effects were documented.
Results: 102 patients completed the trial. Zonisamide showed significantly greater efficacy compared with placebo (responder rate 55.8% vs 36.0%, p < 0.05), including 55.2% (16 of 29 patients) in the zonisamide 300 mg/day arm and 56.5% (13 of 23 patients) in the zonisamide 400 mg/day arm. Zonisamide 300 and 400 mg/day showed similar efficacy (p > 0.05). Moreover, similar efficacy of zonisamide was found in the control of complex partial seizures, simple partial seizures and secondary generalized seizures. There was no difference in the incidence of adverse effects between zonisamide and placebo. Reported adverse effects in the zonisamide group involved the digestive system (32.5% of total adverse effects in the group) [including transient increases in liver enzymes (27.8%)], weight changes (30.2%), the haematological system (15.1%), neurological/psychiatric effects (10.3%), the urinary system (7.9%) and the cardiovascular system (4.0%). Only digestive system adverse effects constituted a significantly higher proportion of adverse effects in the zonisamide group than in the placebo group (32.5% vs 30.2%, p < 0.05).
Conclusion: Zonisamide 300–400 mg/day is effective and well tolerated as an adjunctive drug in adult Chinese patients with refractory partial-onset epilepsy.
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References
Baulac M, Leppik IE. Efficacy and safety of adjunctive zonisamide therapy for refractory partial seizures. Epilepsy Res 2007; 75(2–3): 75–83
Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981; 22(4): 489–501
Brodie MJ. Zonisamide as adjunctive therapy for refractory partial seizures. Epilepsy Res 2006; 68Suppl. 2: 11–6
Zaccara G, Specchio LM. Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat 2009; 5: 249–59
Faught E. Review of United States and European clinical trials of zonisamide in the treatment of refractory partial-onset seizures. Seizure 2004; 13Suppl. 1: 59–65
Brodie MJ, Duncan R, Vespignani H, et al. Dose-dependent safety and efficacy of zonisamide: a randomized, double-blind, placebo-controlled study in patients with refractory partial seizures. Epilepsia 2005; 46(1): 31–41
Faught E, Ayala R, Montouris GG, et al. Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures. Neurology 2001; 57(10): 1774–9
Sackellares JC, Ramsay RE, Wilder BJ, et al. Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures. Epilepsia 2004; 45(6): 610–7
Wu XY, Hong Z, Wu X, et al. Multicenter double-blind, randomized, placebo controlled trial of levetiracetam as add-on therapy in Chinese patients with refractory partial-onset seizures. Epilepsia 2009; 50(3): 398–405
Xiao Z, Li JM, Wang XF, et al. Efficacy and safety of levetiracetam (3,000 mg/day) as an adjunctive therapy in Chinese patients with refractory partial seizures. Eur Neurol 2009; 61(4): 233–9
Yen DJ, Yu HY, Guo YC, et al. A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy. Epilepsia 2000; 41(9): 1162–6
Zhu GX, Ding MP, Xiao B, et al. Curative effect of gabapentin on refractory epilepsy [in Chinese]. Zhonghua Yi Xue Za Zhi 2005; 85(2): 92–5
Cramer JA, Fisher R, Ben-Menachem E, et al. New anti-epileptic drugs: comparison of key clinical trials. Epilepsia 1999; 40(5): 590–600
Tran TA, Leppik IE, White JR, et al. The effect of zonisamide on weight. Epilepsia 2002; 43Suppl. 7: 211
Wellmer J, Wellmer S, Bauer J. The impact of zonisamide on weight: a clinical study in 103 patients with epilepsy. Acta Neurol Scand 2009; 119(4): 233–8
Data on file. Shenzhen Zifu Co. Ltd, 2005
Acknowledgements
No sources of funding were used to assist in the conduct of this study or the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this study. Drs Yang Lu and Zhanqin Xiao contributed to this work equally.
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Lu, Y., Xiao, Z., Yu, W. et al. Efficacy and Safety of Adjunctive Zonisamide in Adult Patients with Refractory Partial-Onset Epilepsy. Clin. Drug Investig. 31, 221–229 (2011). https://doi.org/10.2165/11539750-000000000-00000
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DOI: https://doi.org/10.2165/11539750-000000000-00000