唑尼沙胺添加治疗部分性癫(癎)的临床疗效及安全性:多中心随机双盲安慰剂对照研究

摘要

Objective To evaluate the efficacy and safety of zonisamide (ZNS) as adjunctive therapy in patients with partial seizure or secondary generalized seizure, generalized tonic - clonic seizure (GTCS), absence seizure.Methods In this multicenter, randomized, double - blinded, placebo-controlled trial, 240 patients with confirmed partial seizure were randomly distributed to either ZNS group or placebo group.After a 12-week baseline period, all patients entered a 3-week titration interval, in which the ZNS dose gradually increased from 100mg qd to 100 mg tid, and a 13-week maintenance period.The main criteria of efficacy was measured by control rates and response rates during the period between the fifth week to the sixteenth week.The adverse effects were also counted for the evaluation of safety.Results Thirty-two patients (32/94, 34.04％) in ZNS group and 14 (14/107, 13.08％) in placebo group achieved complete control of seizure; 70 (70/94, 74.47％) in ZNS group and 46 (46/107, 42.99％) in placebo group had seizure frequency decreased by more than 50％ , the rate differences were both statistically significant (P = 0.000, for all).The most common adverse effects included: decreased appetite, drowsiness, fatigue, dizziness, abnormal liver function, et al.The incidence of adverse effects in ZNS group was significantly lower than that in placebo group (P = 0.003).Conclusion Zonisamide for adjunctive therapy is superior to placebo in patients with partial seizure, and is generally well tolerated.It can be a new selective antiepileptic drug.%目的:观察唑尼沙胺分散片添加治疗部分性发作或继发全面性发作、全面性强直-阵挛发作及失神发作的疗效及安全性.方法:240例诊断明确的部分性发作患者,被随机分为唑尼沙胺组(120例)或对照组(120例).回顾性基线期(12周)后,予初始剂量唑尼沙胺或安慰剂100mg/次,1次/d,3周内递增至100mg/次,3次/d;分别在治疗第0、2、4、8和16周时进行随访,评价治疗第5-16周时临床综合疗效的完全控制率和总有效率,以及药物安全性和不良反应.结果:治疗第5-16周时,唑尼沙胺组患者癫(癎)完全控制率为34.04%(32/94)、总有效率74.47%(70/94),对照组分别为13.08%(14/107)和42.99%(46/107);两组临床综合疗效的完全控制率和总有效率比较,差异具有统计学意义(均P=0.000).唑尼沙胺组患者常见药物不良反应包括食欲不振、嗜睡、疲劳、头晕、肝功能异常等,与对照组不良反应发生率比较差异有统计学意义(P=0.003).结论:唑尼沙胺作为添加药物治疗部分性发作或继发全面性发作、全面性强直-阵挛发作的疗效优于安慰剂,而且有较好的安全性和耐受性,是临床可以选择的新型抗癫(癎)药物之一.