唑尼沙胺添加治疗部分性癫的临床疗效及安全性:多中心随机双盲安慰剂对照研究

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100 mg/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。     

随机、双盲、安慰剂对照、多中心研究唑尼沙胺添加用药治疗部分性癫(癎)发作的有效性和安全性

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.     

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

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、全面性强直一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,唑尼沙胺组患者癫痼完全控制率为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、全面性强直一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。     

多中心双盲、随机、安慰剂对照评价左乙拉西坦添加治疗难治性部分性癫(癎)发作的疗效及安全性

目的 评价左乙拉西坦(LEV)添加用药治疗难治性部分性癫(癎)发作的临床疗效及安全性.方法 随机、双盲、安慰剂对照、多中心平行设计添加治疗,确诊为有癫(癎)部分性发作的202例癫(癎)患者,平均年龄(32.8±12.7)岁,随机分配入LEV治疗组(n=102)与安慰剂组(n=100).在回顾8周基线期的癫(癎)发作频率后,进入逐量加药期.初始用药剂量为0.5 g,每日2次,2周后增加至1.0 g,每日2次服用,4周后加量至1.5 g,每日2次,随后维持该剂量治疗12周,最后逐渐减量并转入LEV开放治疗期.主要评价指标为16周治疗期内每周癫(癎)发作频率的比较、得出药物治疗发作频率减少50%有效率、安全性和药物不良反应.结果 在16周治疗期内,LEV组每周癫(癎)发作频率明显减少,较安慰剂组减少26.8%;每周发作频率较基线期下降数在LEV组与安慰剂组的组间差异为42.2%;部分性发作频率减少50%有效率为55.9%,与安慰剂组比的OR值为3.6;有11例治疗后完全无发作,两组相比均有显著统计学意义(P＜0.001).LEV组的主要不良事件为嗜睡、头晕、无力及血小板减少,但与安慰剂组比差异无统计学意义.结论 LEV添加用药治疗成人难治性部分性癫(癎)发作,可以显著减少癫(癎)发作频率,安全性良好.     

多中心、随机、双盲、安慰剂对照评价普瑞巴林添加治疗部分性癫癎发作的疗效和安全性

目的 评价普瑞巴林添加治疗部分性癫（癎）发作的疗效和安全性.方法采用随机、双盲、安慰剂对照、多中心平行设计添加治疗的方法,确诊为有部分性癫（癎）发作的225例癫（癎）患者,被随机分配入普瑞巴林治疗组（114例）与安慰剂组（111例）.在6周前瞻性基线期后,采用灵活剂量的普瑞巴林（150～600 mg·d-1）添加治疗成人部分性癫（癎）发作.主要疗效指标：部分性癫（癎）发作28 d-反应率.次要疗效指标：部分性癫（癎）发作28d-减少率、临床疗效评价、16周内癫（癎）无发作和发作减少率≥50％的病例比例、第13～16周癫（癎）无发作和发作减少率≥50％的病例比例以及临床疗效总评量表评分;并观察研究药物的安全性与不良反应情况.结果 普瑞巴林组部分性癫（癎）发作28 d-反应率（-40.24±37.88）％,显著高于安慰剂组（-22.84±37.61）％（F=15.063 9,P=0.000 l）.普瑞巴林组和安慰剂组的不良事件发生率分别为60.53％和47.75％,组间无显著差异;但普瑞巴林组的不良反应发生率较安慰剂组高（45.61％ vs 23.42％,P=0.000 7）,主要不良反应有头晕、嗜睡、视物模糊、乏力等.结论 普瑞巴林组的疗效显著优于安慰剂组.普瑞巴林作为部分性癫（痈）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.     

左乙拉西坦添加治疗难治性部分陛癫癎的疗效及其与多药耐药基因的相关性研究:随机双盲安慰剂对照临床试验

目的 探讨左乙拉西坦添加治疗难治性部分性癫痢的临床疗效及其与多药耐药基因1(MDRI)的相关性.方法 30例诊断明确的难治性部分性癫癎患者按照随机双盲安慰剂对照研究方法,分别予抗癫癎药物左乙拉西坦添加治疗和安慰剂治疗,初始剂最1 g(2次/d),2周后增至2 g(2次/d),再2周后增至3 g(2次/d),维持治疗12周后逐渐减量,进入减量/开放期.评价患者治疗期(16周)每周癫癎发作频率与回顾性基线期比较降低的百分比及发作频率减少50%的有效率.聚合酶链反应-限制性片段长度多态性检测患者基因型.结果 30例患者中27例完成临床试验.基因型检测共检出CC基因型16例,左乙拉西坦添加治疗组(治疗组)9例(完全控制1例、显效3例、有效2例,发作频率减少50%的有效率为66.67%),安慰剂组7例(仅1例有效,发作频率减少50%的有效率为14.29%),组间比较差异具有统计学意义(Z=-2.013,P=0.042);CT+TT基因型11例,治疗组9例(完全控制1例、显效2例、有效4例,发作频率减少50%的有效率为77.78%),安慰剂组2例.治疗组CC基因型与CT+TT基因型患者疗效比较,差异无统计学意义(Z=-0.193,P=0.888).结论 左乙拉两坦作为难治性部分性癫癎患者的添加治疗药物临床效果良好,其主要药理学机制可能与左乙拉西坦是非多药耐药基因1编码的P-糖蛋白底物有关.     

多中心、随机、双盲、安慰剂对照评价普瑞巴林添加治疗部分性癫发作的疗效和安全性

目的评价普瑞巴林添加治疗部分性癫发作的疗效和安全性。方法采用随机、双盲、安慰剂对照、多中心平行设计添加治疗的方法,确诊为有部分性癫发作的225例癫患者,被随机分配入普瑞巴林治疗组(114例)与安慰剂组(111例)。在6周前瞻性基线期后,采用灵活剂量的普瑞巴林(150~600 mg·d-1)添加治疗成人部分性癫发作。主要疗效指标:部分性癫发作28 d-反应率。次要疗效指标:部分性癫发作28d-减少率、临床疗效评价、16周内癫无发作和发作减少率≥50%的病例比例、第13~16周癫无发作和发作减少率≥50%的病例比例以及临床疗效总评量表评分;并观察研究药物的安全性与不良反应情况。结果普瑞巴林组部分性癫发作28 d-反应率(-40.24±37.88)%,显著高于安慰剂组(-22.84±37.61)%(F=15.063 9,P=0.000 1)。普瑞巴林组和安慰剂组的不良事件发生率分别为60.53%和47.75%,组间无显著差异;但普瑞巴林组的不良反应发生率较安慰剂组高(45.61%vs 23.42%,P=0.000 7),主要不良反应有头晕、嗜睡、视物模糊、乏力等。结论普瑞巴林组的疗效显著优于安慰剂组。普瑞巴林作为部分性癫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。     

下期内容预告

本刊2011年第4期报道专题为抗癫癎药物的疗效与安全性,重点内容包括:新型抗癫癎药物在国内的应用;抗癫癎药性脑病;抗癫癎药物对心血管系统的影响;抗癫癎药物对内分泌及妇女妊娠的影响;抗癫癎药物对血液系统的影响;常用抗癫癎药物在临床应用中出现的皮肤不良反应;抗癫癎药物对患儿生长发育及认知功能的影响;唑尼沙胺添加治疗部分性癫癎有效性与安全性的多中心随机双盲安慰剂对照临床研究;不同底物对难治性癫癎细胞模型中整合素α₂表达的影响;低频重复经颅磁刺激治疗难治性癫癎大鼠模型的作用及对BDNF和NPY表达的影响;中药治疗癫癎的实验前研究     

左乙拉西坦治疗儿童癫(癎)的疗效观察

目的 观察左乙拉西坦(Lev)治疗儿童癫(癎)的疗效.方法 62例癫(癎)患儿(9个月～14岁)根据病情分为Lev单药治疗组(34例)和添加治疗组(28例).Lev的起始剂量为10～20 mg/(kg·d),分两次服用,每1～2周增加10 mg/(kg·d),在4周内增加至27～46 mg/(kg·d),持续服用6个月.观察治疗过程中癫(癎)发作频率、脑电图变化及不良反应;治疗6个月时评定疗效.结果 本组的总有效率和控制率为64.5%和29.0%.单药治疗组和添加治疗组总有效率分别为76.5%及50.0%,完全控制率分别为41.2%及14.3%,两组间差异有统计学意义(P＜0.05～0.01).治疗前13例脑电图出现睡眠中癫(癎)性电持续状态(ESES),治疗后7例消失.22例(35.5%)出现不良反应,表现为食欲下降、呕吐、思睡、头痛头昏、情绪及行为异常,均自行缓解.结论 无论单药还是添加治疗,Lev对儿童癫(癎)均有显著疗效,对ESES有部分改善作用;不良反应轻.     

桂芍镇(癎)片治疗癫(癎)的临床观察

目的观察桂芍镇(癎)片对难治性癫(癎)患者的疗效.方法选择36例不同类型的癫(癎)病历进行半年-1年的疗效观察.结果经36例治疗,显效率11例(30.06%),显著好转及一般好转15例(41.39%),效差及无效10例(28.06%).结论桂芍镇(癎)片对治疗癫(癎)病确实有效,在治疗过程中发现,从发作频度与疗效关系来看,似乎发作频度越高效果越差.从癫(癎)类型与疗效关系来看,以全身性发作为优.     

Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in Chinese patients with refractory partial-onset seizures

Purpose:   To evaluate efficacy and tolerability of levetiracetam (LEV; Keppra^®) as add-on therapy in Chinese patients with refractory partial-onset seizures.
Methods:   In this multicenter, double-blind, randomized, placebo-controlled trial, 206 patients aged 16–70 years with uncontrolled partial-onset seizures were randomized to receive LEV (n =103) or placebo (n =103); 202 patients (LEV, n =102; placebo, n = 100) comprised the intent-to-treat population. An 8-week historical baseline period confirmed eligibility according to seizure count. The 16-week treatment period consisted of a 4-week up-titration period (LEV, 1,000–3,000 mg/day in two equal divided doses) followed by a 12-week maintenance period. Efficacy assessments were based on weekly frequency of partial-onset seizures during the 16-week treatment period.
Results:   LEV significantly decreased weekly partial-onset seizure frequency over placebo by 26.8% (p  < 0.001). Median percentage reductions in weekly partial-onset seizure frequency from historical baseline were 55.9% for LEV and 13.7% for placebo (p  < 0.001). The ≥50% responder rates were 55.9% for LEV, compared with 26.0% for placebo (p  < 0.001). Freedom from partial-onset seizures during treatment period was achieved by 11 LEV patients (10.8%) and 2 placebo patients (2.0%) (p = 0.012). Adverse events were reported by 65 LEV-treated patients (63.1%) and 62 placebo-treated patients (60.2%); most were of mild-to-moderate intensity. The most common adverse events were somnolence (LEV, 17.5%; placebo, 17.5%), decreased platelet count (LEV, 9.7%; placebo, 9.7%), and dizziness (LEV, 7.8%; placebo, 13.6%).
Discussion:   Add-on LEV was effective and well-tolerated in Chinese patients with refractory partial-onset seizures.     

左乙拉西坦添加治疗对难治性部分性癫(癎)患者生活质量影响的研究

目的:评价新型抗癫药物左乙拉西坦(Lev)作为添加治疗对难治性部分性癫患者生活质量的影响。方法:43例确诊有癫部分性发作的成年患者随机分为两组:Lev治疗组与安慰剂组,Lev治疗16周后比较两组的有效率和不良反应,并用QOLIE-31量表对两组癫患者进行生活质量评定,所有患者在转入Lev开放性治疗6个月后再次进行QOLIE评估。结果:16周治疗期末Lev组癫部分性发作的治疗有效率明显高于安慰剂组,两组不良反应的发生率相当;Lev组生活质量明显高于安慰剂组,两组患者转入开放性治疗6个月后,生活质量均显著改善。结论:Lev作为添加用药治疗成人难治性部分性癫发作,显著减少发作频率、安全耐受性较好,能够提高癫患者的生活质量。     

Gabapentin as Add-On Therapy in Children with Refractory Partial Seizures: A 12-Week, Multicentre, Double-Blind, Placebo-Controlled Study

PURPOSE: To evaluate the efficacy and safety of gabapentin (Neurontin; GBP) as add-on therapy for refractory partial seizures in paediatric patients aged 3-12 years. METHODS: After a 6-week baseline period, 247 patients (54 centres) entered a 12-week double-blind phase and were randomized to receive either GBP (t.i.d., titrated to 23-35 mg/kg/ day) or placebo. Seizure activity and type were recorded daily. Efficacy variables included Response Ratio (RRatio), responder rate, and percentage change in frequency (PCH) for all partial seizures; PCH and RRatio for individual types of partial seizures; and investigator and parent/guardian global assessments of seizure frequency and patient well-being. RESULTS: RRatio for all partial seizures was significantly lower (better) for GBP-treated patients (p = 0.0407). Responder rate favored GBP, but the difference between treatment groups was not statistically significant. Median PCH for all partial seizures for the GBP treatment group (-17.0%) was better than that for the placebo group (-6.5%). Median PCH for specific seizure types showed GBP to be most effective in controlling complex partial seizures (-35%) and secondarily generalized seizures (-28%) when compared with placebo (-12%, +13%, respectively). A greater percentage of GBP-treated patients exhibited improvement according to investigator and parent/guardian global assessments, with a statistically significant difference observed in the parent/guardian global assessment of seizure-frequency reduction (p = 0.046). Three GBP patients and one placebo patient were seizure free during the double-blind treatment period. GBP was well tolerated. CONCLUSIONS: GBP was effective and well tolerated as an add-on therapy for partial seizures in paediatric patients with previously drug-resistant seizures.     

Efficacy and safety of levetiracetam in clinical practice: results of the SKATE trial from Belgium and The Netherlands.

OBJECTIVE: Aim of the study was to assess the efficacy and safety of levetiracetam as add-on treatment in patients with partial-onset epilepsy in clinical practice. METHODS: In this observational, multi-centre study patients were treated with levetiracetam for 16 weeks. From a starting dose of 1000 mg/day, dose levels were adjusted at 2-weekly intervals in 1000-mg steps, to a maximum of 3000 mg/day, based on seizure control and tolerance. Analysis of efficacy was based on reduction in seizure frequency relative to baseline, 50% and 100% responder rates (for partial seizures and all seizure types combined) and percentage of patients using levetiracetam at the end of the study. Analysis of safety was based on occurrence of adverse events. RESULTS: The present analysis concerns the results of patients recruited in Belgium and The Netherlands. Of the 251 patients included in the study, 86.9% completed 16 weeks of treatment. Reduction in frequency of partial-onset seizures was 62.2%, with 19.3% of the patients becoming seizure free and 56.6% having a reduction in seizure frequency of > or = 50%. These percentages were more or less the same when calculated for all seizure types combined. Tolerance of levetiracetam treatment was good, with most adverse events being only mild to moderate in severity, and only 10.0% of the adverse events leading to discontinuation from the study. Asthenia, somnolence, dizziness and headache were the most frequently reported adverse events. CONCLUSION: Levetiracetam is effective and safe as add-on treatment for partial-onset seizures in clinical practice.     

Efficacy and safety of levetiracetam 1000-3000 mg/day in patients with refractory partial-onset seizures: a multicenter, open-label single-arm study

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam as add-on therapy in patients with refractory partial-onset seizures in a protocol designed to reflect clinical practice. METHODS: All patients in this open-label, single-arm study entered an 8-week baseline period followed by a 4-week titration period and a 12-week maintenance period. Patients initially received levetiracetam 1000 mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to 3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of levetiracetam could not be increased but could be decreased once if tolerability warranted. Seizure count and adverse events were recorded by patients in a diary. Quality of life and global evaluation of disease evolution were also evaluated. RESULTS: Ninety-nine patients were enrolled and 91 completed the study. A steady dose was maintained over the last 8 weeks of treatment or longer in 84 patients, with 89.3% of these patients receiving 3000 mg/day, 9.5% receiving 2000 mg/day, and 1.2% receiving 1000 mg/day. A 35.9% median percent reduction from baseline in weekly frequency of partial-onset seizures was observed over the entire treatment period. The median partial-onset seizure count decreased from 2.3 per week during the baseline period to 1.3 per week over the treatment period. A total of 42.4% of patients were responders (> or = 50% reduction from baseline in weekly seizure frequency) over the treatment period; two patients were seizure-free from the first day of treatment throughout the treatment period. The most frequent drug-related adverse events were fatigue (27.3% of patients), somnolence (11.1%), headache (8.1%), and dizziness (8.1%). CONCLUSION: Levetiracetam as add-on therapy at doses up to 3000 mg/day effectively reduced the frequency of partial-onset seizures in patients with refractory epilepsy and was well-tolerated in this study, bridging conditions of placebo-controlled clinical trials and clinical practice.     

Dose-dependent safety and efficacy of zonisamide: a randomized, double-blind, placebo-controlled study in patients with refractory partial seizures

PURPOSE: To evaluate the safety and efficacy of zonisamide (ZNS) as adjunctive treatment in patients with refractory localization-related epilepsy. METHODS: This was a double-blind, placebo-controlled study of adjunctive ZNS in 351 patients with refractory partial seizures receiving a stable regimen of one to three antiepileptic drugs (AEDs). Patients were randomized to placebo or ZNS, 100 mg, 300 mg, or 500 mg/day (2:1:1:2) after a 12-week baseline. Dose titration was undertaken over a 6-week titration phase, which was followed by an 18-week fixed-dose assessment phase. Primary efficacy parameters were the differences between ZNS, 500 mg/day, and placebo in the change from baseline in frequency of complex partial (CP) seizures during the fixed-dose assessment phase and in the proportion of CP responders (> or =50% decrease from baseline in seizure frequency). Safety and tolerability also were assessed. RESULTS: Compared with placebo, the highest dose of ZNS (500 mg/day) resulted in a significantly greater decrease in CP seizure frequency from baseline (51.2% vs. 16.3%; p < 0.0001) and a significantly higher proportion of CP responders (52.3% vs. 21.3%; p < 0.001). Both ZNS, 500 mg/day, and 300 mg/day were statistically superior to placebo in reducing the frequency of "all seizures" and simple partial (SP) + CP seizures. For all seizures, a significant dose-response relation was observed (p < 0.0001).The most common adverse events were somnolence, headache, dizziness, and nausea during the titration phase and headache and pharyngitis during the fixed-dose assessment phase. CONCLUSIONS: ZNS provides dose-dependent, effective, and generally well-tolerated adjunctive therapy in patients with partial seizures.     

Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV, Keppra) as add-on therapy in patients with refractory partial seizures. METHODS: In this European multicenter, double-blind, randomized, placebo-controlled trial, LEV (500 or 1,000 mg twice daily) was compared with placebo as add-on therapy in 324 patients with uncontrolled simple or complex partial seizures, or both, with or without secondary generalization. After enrollment, three parallel groups were assessed during a baseline period of 8 or 12 weeks, followed by a 4-week titration interval and a 12-week evaluation period. RESULTS: LEV significantly decreased partial seizure frequency compared with placebo. A reduction in seizure frequency of > or =50% occurred in 22.8% of patients in the 1,000-mg group and 31.6% of patients in the 2,000-mg group, compared with 10.4% of patients in the placebo group. Administration of LEV did not affect plasma concentrations of concomitant antiepileptic drugs or alter vital signs or laboratory parameters. No significant difference in the incidence of adverse events was observed between treatment groups (70.8% for the 1,000-mg group and 75.5% for the 2,000-mg group), or between the LEV and placebo groups (73.2% for placebo group). The most commonly reported adverse effects in the LEV group were asthenia, headache, and somnolence. CONCLUSIONS: The antiepileptic efficacy and tolerability of LEV (1,000 mg/d and 2,000 mg/d, administered in two divided doses) as add-on therapy was established in patients with refractory partial seizures in this clinical study.