多中心、随机、双盲、安慰剂对照评价唑尼沙胺添加治疗癫(癎)部分性发作的疗效和安全性

目的 评价唑尼沙胺作为添加治疗癫(癎)部分性发作的疗效和安全性.方法 确诊为有癫(癎)部分性发作的217例癫(癎)患者,随机分配入唑尼沙胺治疗组(n=111)与安慰剂组(n=106)进行随机、双盲、安慰剂对照、多中心平行设计添加治疗.在3个月回顾性基线期后,给予患者初始剂量唑尼沙胺(100 mg/片)或安慰剂每次1片,每日1次口服,4周内递增至每次2片,每日2次.分别在治疗0、2、4、8、12和16周时进行随访.主要疗效指标为治疗结束后与基线期比较发作次数减少的中位百分比;次要疗效指标为发作次数减少大于50%的比例.同时观察研究药物的安全性与不良反应情况.结果 总发作次数减少率中位数在唑尼沙胺组为33.33%,安慰剂组为0;唑尼沙胺组总发作次数减少>50%者38例(34.23%),安慰剂组21例(19.81%),差异有统计学意义(χ3=5.7159,P=0.0168).唑尼沙胺组治疗后无发作13例(11.71%),有效25例(22.52%),临床有效率为34.23%;安慰剂组无发作5例(4.72%),有效16例(15.09%),临床有效率为19.81%,2组间比较差异有统计学意义(U=2.4701,P=0.0135).唑尼沙胺组与安慰剂组比较,其不良反应发生率差异无统计学意义,唑尼沙胺组较常见的不良反应有思睡、乏力、食欲下降、胃肠道不适、失眠和便秘.结论 唑尼沙胺作为部分性癫(癎)发作的添加药物有确定的疗效,安全耐受性较好,具有一定临床应用价值.

Multicenter randomized, double-blind, placebo-controlled trial of zonisamide as add-on therapy in patients with refractor partial seizures

Objective To evaluate the efficacy and tolerability of zonisamide (ZNS) as add-on therapy in patients with refractory partial seizures.Methods In this Chinese muiticenter, double-blind, randomized, placebo-contrclled trial, ZNS was compared with placebo add-on therapy in 217 patients (intent-to treat (ITT) population) with uncontrolled partial-onset seizures.All patients entered a 3-month baseline period followed by a 4-week titration interval and a 12-week maintenance period.The starting dose of ZNS group was 100 mg/d, increased by 100 mg/d every week and reached the goal of 400 mg/d.The main outcome was measured by the median of the percentage of decreased seizure frequency.The secondary ouwomes points included the percentage of patients who had seizure attacks decreased by more than 50%,and adverse events.Results The median of the percentage of decreased seizure frequency in ZNS group was 33.33%, and the placebo group was 0.Thirty-eight patients (34.23%) experienced more than 50% reduction in the seizure frequency in ZNS group, compared with 19.81% of patients (21 cases) in the placebo group (χ2 =5.7159,P =0.0168) ; Moreover, 13 (11.71%) patients in ZNS group and 5 patients in placebo group were seizure free, 25 patients in ZNS group and 16 patients in placebo group who had seizure attacks decreased by more than 50%.The availability rate in ZNS group was higher than placebo group (34.23% vs 19.81%, U=2.4701, P=0.0135).The most common adverse events in ZNS group were drowsiness, fatigue, decreased appetite, gastrointestinal complaints, insomnia and constipation.Conclusion Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency as adjunctive treatment for partial-onset seizures.