托吡酯多中心开放性添加治疗成人难治性癫痫部分性发作的临床观察

目的 评价托吡酯（topiramate,TPM)对难治性癫痫部分性发作的疗效及耐受性。方法 采用多中心开放性试验的方法对全国52家医院的431例病人进行托吡酯添加治疗。本研究包括8周基础期、8周加量期及12周稳定观察期。在8周基础期,病人虽用1－3种抗癫痫药治疗,但仍有每月至少4次的发作;在加量期,TPM开始量为25mg/d,持续1周,以后每周增加25mg/d,直到目标剂量达到200mg/d,维持此剂量12周为稳定观察期。结果 431例病人参加此项研究,其中癫痫发作频率减少≥50％者为326例（75．6％）,≥75％者为257例（59．6％）,减少100％者为91例（21．1％）。18例（4．2％）发作频率增加≥25％。就发作类型而言,癫痫发作频率减少 ≥50％者中,单纯部分性发作（SPS）为83．4％,复杂部分性发作（CPS）为74．4％,部分发作继发全身性发作为82．1％。未出现严重的副作用。结论 TPM对癫痫部分性发作伴有或不伴有继发全身性发作者有效,口服安全。     

托吡酯单药治疗全身强直-阵挛发作癫痫48例的疗效观察

目的研究托吡酯(TPM)单药治疗全身强直-阵挛发作(GTCS)癫癎的疗效和安全性.方法对48例GTCS患者(成人31例,儿童17例;特发性GTCS 32例,症状性GTCS 16例)给予TPM单药治疗20周.以基础期平均每月发作频率分别与加量期和稳定期平均每月发作频率进行比较,并观察治疗前后脑电图(EEG)的变化和药物的安全性.结果单药治疗20周后,与基础期比较,85.42%(41例)患者发作频率降低≥50%;66.67%(32例)患者发作频率降低≥75%;37.50%(18例)患者完全不发作.特发性GTCS总有效率(93.75%)高于症状性GTCS(68.75%)(P<0.01).治疗后EEG异常率(35.42%)较治疗前(64.60%)明显下降(P＜0.01).无明显不良反应.结论 TPM单药治疗GTCS的总有效率与丙戊酸钠、苯妥英钠相近,治疗后EEG有显著性改善,有良好的耐受性.TPM为GTCS单药治疗的有效药物之一.     

托吡酯单药治疗全身强直-阵挛发作癫癎48例的疗效观察

目的研究托吡酯(TPM)单药治疗全身强直-阵挛发作(GTCS)癫癎的疗效和安全性.方法对48例GTCS患者(成人31例,儿童17例;特发性GTCS 32例,症状性GTCS 16例)给予TPM单药治疗20周.以基础期平均每月发作频率分别与加量期和稳定期平均每月发作频率进行比较,并观察治疗前后脑电图(EEG)的变化和药物的安全性.结果单药治疗20周后,与基础期比较,85.42%(41例)患者发作频率降低≥50%;66.67%(32例)患者发作频率降低≥75%;37.50%(18例)患者完全不发作.特发性GTCS总有效率(93.75%)高于症状性GTCS(68.75%)(P<0.01).治疗后EEG异常率(35.42%)较治疗前(64.60%)明显下降(P＜0.01).无明显不良反应.结论 TPM单药治疗GTCS的总有效率与丙戊酸钠、苯妥英钠相近,治疗后EEG有显著性改善,有良好的耐受性.TPM为GTCS单药治疗的有效药物之一.     

托吡酯单药治疗全身强直-阵挛发作癫48例的疗效观察

目的　研究托吡酯 (TPM)单药治疗全身强直 阵挛发作 (GTCS)癫疒间 的疗效和安全性。方法　对4 8例GTCS患者 (成人 31例 ,儿童 17例 ;特发性GTCS 32例 ,症状性GTCS 16例 )给予TPM单药治疗 2 0周。以基础期平均每月发作频率分别与加量期和稳定期平均每月发作频率进行比较 ,并观察治疗前后脑电图 (EEG)的变化和药物的安全性。结果　单药治疗 2 0周后 ,与基础期比较 ,85 4 2 % (4 1例 )患者发作频率降低≥ 5 0 % ;6 6 6 7% (32例 )患者发作频率降低≥ 75 % ;37 5 0 % (18例 )患者完全不发作。特发性GTCS总有效率 (93 75 % )高于症状性GTCS(6 8 75 % ) (P <0 0 1)。治疗后EEG异常率 (35 4 2 % )较治疗前 (6 4 6 0 % )明显下降 (P <0 0 1)。无明显不良反应。结论　TPM单药治疗GTCS的总有效率与丙戊酸钠、苯妥英钠相近 ,治疗后EEG有显著性改善 ,有良好的耐受性。TPM为GTCS单药治疗的有效药物之一。     

妥泰治疗难治性癫痫的临床疗效观察

目的：观察妥泰（TPM）单药对难治性癫痫（RE）的临床疗效和安全性。方法：RE41例，添加TPM治疗后逐渐撤去原服用的抗癫痫药物，而用TPM单药治疗。以添加TPM前12周平均每4周发作频率为基线，与评价前12周平均每4周发作频率进行个体自身比较。按常规计算完全控制率和有效率。并进行临床观察和实验室检查。结果：完全控制率34．1％，有效率65．9％。不良反应25例次, 但绝大部分轻微，可自行消失。结论：TPM对RE疗效显著，安全性好。     

托吡酯治疗难治性癫痫的疗效观察

目的：临床临床观察托吡酯（TPM）对难治性癫的疗效和安全性。方法：观察总结21例难治性癫痫病人，在原来应用抗癫痫药物（AEDs）种类及剂量不变的基础上，另增添TPM后3个月与治疗前1个月，癫痫发作频度进行个体自身比较。结果：完全被控制率38．1％，好转率33．3％，总有效率71．4％，不良反应轻微。结论：TPM治疗各类难治性癫痫的疗效显著，安全性好。     

妥泰添加及药物转换治疗儿童癫痫94例疗效观察

目的　观察妥泰 ( TPM)添加治疗儿童癫痫的疗效及癫痫发作完全控制后转换为 TPM单药治疗的可行性。方法　对 94例应用一线抗癫痫药控制不满意的患儿 ,其中部分性发作 ( PS) 5 2例 ,全身性发作 ( GS) 4 2例 ,在原用抗癫痫药 ( AEDs)的基础上加用 TPM 0 .5～ 1.0 mg/ kg.d,日 2次 ,口服 ,每 5～ 7d加量一次 ,直至达到目标剂量。治疗 12周后根据发作频率将疗效分为完全控制、显效、有效和无效。对发作完全控制后的癫痫患儿 8～ 12周后 ,逐渐减去其它抗癫痫药 ,转换为 TPM单药治疗。结果　 5 2例 PS患儿应用 TPM治疗后得到完全控制 2 9例 ,显效 10例 ,有效 6例 ,无效 7例 ,总有效率为 86 .5 %;42例 GS患儿治疗后完全控制 16例 ,显效 9例 ,有效 8例 ,无效9例 ,总有效率为 78.6 %;在完全控制发作的 2 9例 PS中 ,及 GS的 16例中 ,转换为单用 TPM治疗达 2个月以上尚未见发作的分别为 7例、4例。94例加用 TPM后 2 9例出现的不良反应 ,占 30 .9%,其中以食欲减退多见 ,其次为困倦及体重下降等 ,在加量期过后大多消失 ,治疗前后血、尿常规、肝、肾功能未发现有临床意义的改变。结论　 TPM是一种广谱、高效、安全的 AEDs,适用于小儿各型癫痫的联合和单药治疗。     

托吡酯添加治疗对难治性癫痫的临床观察

目的 观察添加托吡酯（TPM）对难治性癫痫（IE）的临床效果与安全性。方法 观察IE15例，以加用TPM前1个月的发作频率为基准，按规定添加TPM，并与加TPM后稳定期3个月中最后1个月的发作频率进行比较，比观察疗效，同时观察副作用。以测原用抗癫痫药（AED）治疗前后的血浓度，协助观察患者用药的依从性。结果 患者用药依从性好，有效率为42.1％－46.7％。对多型癫痫发作有效。副反应轻至中度，且多为一过性。结论 加用TMP治疗IE是安全有效的选择方法之一。     

丙种球蛋白佐治小儿难治性癫疗效分析

目的探讨丙种球蛋白佐治小儿难治性癫的疗效。方法对30例难治性癫在原用抗癫药物(AEDs)不变的基础上,加用丙种球蛋白0.4mg/(kg.d),3～5d辅助治疗。主要观察治疗前后发作频率的改变情况,不良反应及其对原用抗癫药物血药浓度的影响。结果显效8例,有效10例,无效12例。不良反应较少。结论加用丙种球蛋白可提高小儿难治性癫的疗效,且不影响其他抗癫药物的血药浓度。     

拉莫三嗪加治难治性癫痫均期1年的临床观察

观察拉莫三嗪（ＬＴＧ）加治难治性癫痫（ＩＥ）４０例均期１年的临床效果和副反应。结果：发作频率减低≥５０％的病人占６０％（２４／４０），加用ＬＴＧ治疗后月均发作频率较治疗前明显减低，总月均频率下降８８．４％（Ｐ＜０．００１）。ＬＴＧ对各型发作均有效。其与ＶＰＡ合用可显著地提高临床疗效。ＬＴＧ耐受性较好，副反应主要为皮疹。说明ＬＴＧ为新型广谱ＡＥＤｓ，较为安全，但应警惕过敏性皮疹     

Topiramate in refractory epilepsy: a prospective observational study

PURPOSE: This prospective observational study explored the efficacy and tolerability of topiramate (TPM) in patients with refractory epilepsy attending a single outpatient clinic. METHODS: One hundred seventy patients (82 men, 88 women, aged 18-75 years) with refractory localization-related (n = 134) or idiopathic generalized epilepsy (n = 36) were started on adjunctive TPM using a standard titration schedule. TPM was introduced after a 3-month prospective baseline, and doses were adjusted according to clinical response. End points were seizure freedom for 6 months, > or =50% seizure reduction for 6 months compared with baseline at the highest tolerated TPM dose (responder), or discontinuation of TPM because of side effects, lack of efficacy, or both. RESULTS: Thirty-nine (23%) patients were seizure-free, and 80 (47%) more patients had a useful therapeutic response. Thirteen seizure-free patients and 16 responders took 100 mg of TPM daily or less. TPM was discontinued in 51 (30%) patients. The most common side effects resulting in withdrawal were fatigue, weight loss, irritability, paresthesia, depression, and headache. Concomitant antiepileptic drugs (AEDs) were stopped in 30 patients. Twelve were established on TPM monotherapy, eight of whom remained seizure-free. Final TPM doses and concentrations varied widely among the three outcome groups. CONCLUSIONS: TPM was efficacious as add-on and monotherapy in patients with refractory partial and generalized seizures in everyday clinical use. A good response was obtained in many patients with TPM doses substantially lower than those studied in regulatory clinical trials. The wide variation in dose-response and dose-toxicity relationships may reflect different neurobiologies causing refractory epilepsy and differential efficacy of AED combinations.     

Topiramate in medically intractable partial epilepsies: double-blind placebo-controlled randomized parallel group trial. Korean Topiramate Study Group

Summary: Purpose: To evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in medically intractable partial epilepsies. Methods: We used a multicenter double-blind placebo-controlled randomized parallel-group trial consisting of 12 weeks of baseline phase, 10 weeks of titration phase, and 8 weeks of stabilization phase. The primary efficacy variable was the median seizure frequency reduction rate (MSFRR), and the other efficacy variables included responder rate, seizure-free rate, and global evaluations by the patient and the physician. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs (AEDs) and should have two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of study drugs was 600 mg/day. The study drugs were started at the initial dose of 50 mg/day and gradually increased to the target dose over a 10-week period. Results: A total of 177 patients was randomized into the TPM group (n = 91) and the placebo (PLC) group (n = 86). Baseline median seizure frequencies were 5.6 episodes/4 weeks in the TPM and the PLC groups. Among those who were randomized, 174 patients (TPM, 89 patients; PLC, 85 patients) were available for the efficacy measurement by intention-to-treat analysis. The MSFRR was 51.3% for TPM and 9.1% for PLC, which was highly in favor of TPM (p = 0.0001). The responder rate was 50.6% for TPM and 12.9% for PLC (p = 0.001). Seven (7.9%) of 89 patients taking TPM became seizure free compared with one (1.2%) of 85 patients taking PLC (p = 0.004). The global evaluation greatly favored TPM (p = 0.001). The incidence of adverse events (AEs) was higher in the TPM (81.3%) than in the PLC (48.9%) group, with central nervous system (CNS)-related AEs being the most frequent. Among individual AEs, anorexia (20.9%) and abdominal pain or discomfort (20.9%) were the most common AEs in the TPM group. AEs precipitated early drop-out in seven (7.6%) patients taking TPM and three (3.5%) patients taking PLC. No serious systemic AEs were observed. Conclusions: TPM was highly effective and safe as add-on therapy in medically intractable partial epilepsies. Slower titration of TPM might be responsible for the lesser drop-out rate than previous trials, but the incidence of AEs was still high. The AE profile of TPM in Koreans was different from that in whites.     

Topiramate in patients with learning disability and refractory epilepsy

PURPOSE: Management of seizures in learning disabled people is challenging. This prospective study explored the efficacy and tolerability of adjunctive topiramate (TPM) in patients with learning disability and refractory epilepsy attending a single centre. METHODS: Sixty-four patients (36 men, 28 women, aged 16-65 years) were begun on adjunctive TPM after a 3-month prospective baseline on unchanged medication. Efficacy end points were reached when a consistent response was achieved over a 6-month period at optimal TPM dosing. These were seizure freedom or > or =50% seizure reduction (responder). Appetite, behaviour, alertness, and sleep were assessed by caregivers throughout the study. RESULTS: Sixteen (25%) patients became seizure free with adjunctive TPM. There were 29 (45%) responders. A further 10 (16%) patients experiencing a more modest improvement in seizure control continued on treatment at the behest of their family and/or caregivers. TPM was discontinued in the remaining nine (14%) patients, mainly because of side effects. Final TPM doses and plasma concentrations varied widely among the efficacy outcome groups. Many patients responding well to adjunctive TPM did so on < or =200 mg daily. Mean carer scores did not worsen with TPM therapy. CONCLUSIONS: TPM was effective as add-on therapy in learning-disabled people with difficult-to-control epilepsy. Seizure freedom is a realistic goal in this population.     

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.     

A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy

PURPOSE: The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study. METHODS: A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placebo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial. RESULTS: In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a > or =50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group. CONCLUSIONS: TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.     

Clinical effects of topiramate against secondarily generalized tonic--clonic seizures

OBJECTIVE: Intensive and quantitative evaluation of the duration, intensity and frequency of tonic and clonic signs of secondarily generalized tonic-clonic seizures (GTCS) in patients with pharmacoresistant partial seizures during topiramate (TPM) treatment. METHODS: Thirty patients suffering from refractory partial seizures with secondarily GTCS undergoing presurgical evaluation were randomized into a low dosage (100 mg daily) and a parallel medium dosage (200 mg daily) group of TPM add-on medication (15 patients for each group). Study phases included a 3 days baseline video-EEG phase, a 10 days TPM titration phase without video-EEG and a 3 days TPM dose maintenance phase with video-EEG. During the baseline and the dose maintenance phase seizures were recorded using video-EEG monitoring and the following parameters were measured for each recorded secondarily generalized tonic and clonic signs: duration (lasting seconds), intensity (on a 0-3 scale), frequency (numbers per 24 h). RESULTS: A total of 46 complex partial seizures with secondarily generalized tonic-clonic signs during the baseline phase and 20 during the dose maintenance phase were intensively analyzed. More patients in the medium dosage group than in the low dosage groups were free from secondarily GTCS during the dose maintenance phase (nine vs. two, P<0.05). Intergroup comparison suggested that the duration of all tonic signs decreased more in the medium dosage group computing the reduction from baseline to the dose maintenance phase (P<0.05). There were statistically more significant reductions in the duration and intensity of clonic signs in the medium dosage group (P<0.05). CONCLUSION: TPM has an early dose-dependant effect on secondarily GTCS in patients with pharmacoresistant partial seizures. SHORT COMMUNICATION: The present study intensively analyzed the duration, intensity, and frequency of secondarily generalized tonic and clonic signs in patients with pharmacoresistant partial seizures. The quantitative data suggested that TPM had a robust early inhibitory effect on secondarily generalized tonic-clonic signs; effects were more prominent in the medium dosage group (200 mg daily) than in the low dosage group (100 mg daily).     

妥泰添加治疗Lennox—Gastaut综合征的临床观察

目的：研究妥泰辅助治疗Lennox-Gastaut综合征的安全性。方法：C地13例Lennox-Gastaut综合征患者进行妥泰进行的添加、开放性自身对照研究，以治疗前3个月的发作频度为基础，治疗后平均观察12个月（6－20月）。结果应用妥泰后，3例患者（23．1％）癫痫发作停止，6例（46．2％），癫痫发作频度减少≥50％，总有效率69．3％，妥泰对Lennox-Gastaut综合征的各型癫痫发作均有较好效果。脑电图有改善的倾,妥泰受性较好，治疗前后各项实验室检查未见有临床意义的异常改变。结论：妥泰是辅助Lennox-Gastaut综合征的一种实安全，有效的新型抗癫痫药。     

Postmarketing experience with topiramate and cognition

Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited central nervous system (CNS) side effects. However, CNS-related treatment-emergent adverse events (TEAEs) often occur in patients receiving AEDs. Topiramate (TPM) is an AED proven to be safe and effective as adjunctive treatment for epilepsy patients with partial seizures. Double-blind, placebo-controlled, multicenter trials demonstrated potential effects on cognition. The P.A.D.S. (post-marketing antiepileptic drug survey) group, a cooperative group of 14 epilepsy centers that collaborate on obtaining data about new AEDs and devices, prospectively collected standardized data forms before and during treatment with TPM for epilepsy, and analyzed the postmarketing experience of CNS TEAEs with TPM. Our results from 701 treated patients show that cognitive complaints were the most common reason to discontinue TPM. The presence of complaints did have predictive value if the patient would discontinue TPM, although was not specific as to when discontinuation would occur. The spectrum of complaints in our open-label prospective multicenter postmarketing study was similar to those observed in controlled clinical trials. We were unable to demonstrate a specific population, dose titration, or concomitant AED that was at risk to discontinue treatment. We conclude that most patients treated with TPM will continue therapy beyond 6 months. Cognitive complaints and not efficacy reflect the primary reason for discontinuing therapy. Psychomotor slowing was the most common complaint, yet most patients elect to continue treatment, with "better" or "much better" ratings of both seizure and global improvement during treatment.