A randomized,double-blind,placebo-controlled,multicenter study to evaluate the efficacy and safety of zonisamide as adjunctive treatment in patients with refractory partial seizures

目的 评价唑尼沙胺(ZNS)作为添加用药治疗部分性癫(癎)发作的有效性和安全性.方法 采用多中心、随机、双盲、安慰剂对照、平行组、添加治疗设计.240例确诊为癫(癎)部分性发作的受试者按照1:1的比例随机分配到ZNS治疗组或安慰剂组.在前4周加鼋期内受试者自100 mg/d逐渐加量至300 mg/d,随后进入12周的稳定治疗期.在稳定期内可根据患者情况酌情减量,或加量至最大剂量400 mg/d.有效性评价的主要指标为稳定期部分性癫(癎)发作频率较基线值减少百分数的中位值,重要的次要评价指标为有效率,即部分性癫(癎)发作次数减少≥50%者的比例.同时对药物的安全性进行评价.结果 ZNS组受试者稳定期部分性癫(癎)发作频率较基线期减少百分数(48.4%)显著高于安慰剂组(26.6%),组间差异有统计学意义(F=4.904,P=0.028);ZNS组治疗部分性癫(癎)发作的有效率(48.6%)高于安慰剂组(34.9%),差异有统计学意义(X2=4.046,P=0.044),其中以复杂部分性癫(癎)的组间差异最为显著(分别为52.2%和33.3%,X2=5.607,P=0.018).ZNS组与安慰剂组不良事件发生率相当,与ZNS相关的不良事件多为头晕、头痛、嗜睡、食欲下降、恶心等.结论 ZNS能有效治疗部分性癫(癎),降低癫(癎)发作频率,对复杂部分性癫(癎)发作治疗效果尤为突出.ZNS耐受性良好,受试者用药安全性较高.Objective To evaluate the safety and efficacy of Zonisamide(ZNS) as adjunctive therapy in patients with refractory partial seizures receiving other antiepileptic drags (AEDs).Methods This was a randomized,double-blind,placebo-controlled study conducted at multi-centers.All 240 subjects were randomized to either the ZNS group or the placebo group in a 1:1 ratio.The double-blind treatment phase included a titration phase during which zonisamide dose inereased from 100 mg/day to 300 mg/day over 4 weeks and then a 12-week fixed-dose phase.The primary efficacy endpoint was,the median % reduction from baseline in all pattial seizure frequency(CPS+SPS+SGS)during the fixed-dose phase.The important secondaw endpoint wag the responder rate.Safety profiles and tolerance were also evaluated.Results The FAS analysis showed the median reduction from baseline in the ZNS group was greater than in the placebo group(48.4%vs 26.6%),the difference was significant for ZNS compared with placebo(F=4.904,P=0.028);The responder rates for all partial seizures(48.6%vs34.9%,X2=4.046,P=0.044)and for complex seizures(52.2% vs 33.3%,X2=5.607,P=0.018)were significantly higber in the ZNS group than in the placebo group in the FAS population.The overall adverse events(AEs)profile was comparable between the two groups.The most frequent AEs considered to be related to zonisamide by the investigator were headache,dizziness,somnolence,anorexia,nausea,etc.Conclusions ZNS is superior to placebo in reducing the frequency of partial seizures and well-tolerated.ZNS could be a choice of adjunctive therapy in patients with refractory partial seizures.中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)07459-4634