托吡酯添加治疗难治性癫痫临床观察

托吡酯的结构与现在的抗癫痫药完全不同 ,是一种在1982年由johnson实验室首先合成的一种可以替代的单糖类抗癫痫药。主要通过阻滞电压激活钠通道 ,在某种GABA受体上增强GABA的活性 ,或者通过阻滞红藻氨酸AMPA型谷氨酸受体起作用 ,其碳酸酐酶的弱抑制作用与某些副作用有关。主要用于顽固性部分性发作的添加治疗 ,部分性发作继发全面性强直 -阵挛发作 (generalizedtonic -clonicseizure ,GTCS)的治疗 ,也可单药治疗。我院自 2 0 0 0年 4月开展了应用托吡酯添加治疗难治性癫痫 ,疗效显著而副作用较少 ,现报道如下。1　资料与方法1.1　一…     

托吡酯添加治疗难治性癫痫的临床观察

目的 观察添加托吡酯对难治性癫痫的临床效果与副作用。方法 对18例难治性癫痫患者，加用TPM后观察其发作频率并与加用前进行比较。计算总有效率，同时进行临床疗效和副作用观察。结果 病人加用托吡酯后总有效率为50%。其中显效率达22.2%(3例未再发作），副反应以胃肠道反应及神经系统症状为主，发生率为52.6%。结论 加用TPM治疗难治性癫痫安全有效。     

托吡酯加用及单用治疗老年癫痫发作的临床观察

目的 观察加用及单用托吡酯二种方式治疗老年癫痫患者的临床疗效和副反应，探讨单用托吡酯更快、更有效的给药方式。方法 老年癫痫患者124人，分为加用组（A组）：52例患者，在服用卡马西平或苯妥英钠的基础上加用托吡酯25 mg／d，增量25 mg／周至200 mg／d；单药组：72例患者按初始剂量及加量速度不同又分为M1、M2、M3组，M1组患者托吡酯25 mg／d，增量25 mg／周至200 mg／d；M2组患者托吡酯初始剂量50 mg／d，增量25 mg／周至200 mg／d，M3组患者托吡酯初始剂量50 mg／d，增量25 mg／3 d至200 mg／d。结果 各组患者托哟酯总有效率分别为加用组82．7％，单药组初始剂量25 mg／d组82．6％，初始剂量50 mg／d，增量25 mg／周组84．0％，初始剂量50 mg／d，增量25 mg／3 d组70．8％，加用组和M1、M2组单用托吡酯总有效率比较无明显差异（P＞0．05）。发生率比较高的副反应为感觉异常、食欲差和头痛。结论 可单用托吡酯并给予较大初始剂量（50 mg／d），以25 mg／周速度增量治疗老年癫痫。     

托吡酯单药治疗癫痫的临床观察

目的 观察托吡酯(TPM)单药治疗癫痫的临床疗效和不良反应。方法 应用TPM治疗64例癫痫患者，平均日剂量为138mg，服药6～36个月，将每例患者治疗最后3个月的发作次数与基础期比较，并观察记录其不良反应。结果本组总有效率为78．1％，其中控制率为42．2％。不良反应的发生率为70．3％，中枢神经系统的不良反应占57．1％，多数较轻微且持续时间较短。l0例(15．6％)因治疗无效、不良反应或经济等原因终止治疗。结论 TPM长期单药治疗癫痫疗效明显，耐受性好，较为安全。     

托吡酯治疗癫痫的临床观察

目的:本文观察应用托吡酯(妥泰)治疗癫痫的效果及安全性。方法:57例癫痫病人给予口服托吡酯,观察不同发作类型、年龄、用药方法、病程长短及影像改变与疗效的关系。结果:托吡酯对部分性、全面性发作及婴儿痉挛均有效,不良反应较轻。结论:托吡酯是一广谱、安全、有效的新型抗癫痫药物。     

托吡酯治疗难治性癫痫的疗效观察

目的 评价托吡酯（TMP）添加治疗难治性癫痫的疗效和其不良反应，以及对原服用AEDs血中浓度的影响。方法 采用开放性试验的方法对80例难治性癫痫进行添加托吡酯治疗，观察其疗效。结果 托吡酯作为添加治疗难治性癫痫总有效率58.6%。对单纯部分性发作有效率66.7%。复杂部分性发作25%，且完全控制率12.9%，不良反应均与CNS有关，多为一过性，但儿童的无汗，体重减轻，持续时间长，原服用AEDs血中浓度在添加托吡酯前后无明显变化。结论 托吡酯治疗难治性癫痫有效，但要注意用药量的个体化。     

托吡酯加用及单用治疗老年癫痫间发作的临床观察

目的观察加用及单用托吡酯二种方式治疗老年癫痫间患者的临床疗效和副反应,探讨单用托吡酯更快、更有效的给药方式。方法老年癫痫间患者124人,分为加用组(A组)52例患者,在服用卡马西平或苯妥英钠的基础上加用托吡酯25mg/d,增量25mg/周至200mg/d;单药组72例患者按初始剂量及加量速度不同又分为M1、M2、M3组,M1组患者托吡酯25mg/d,增量25mg/周至200mg/d;M2组患者托吡酯初始剂量50mg/d,增量25mg/周至200mg/d;M3组患者托吡酯初始剂量50mg/d,增量25mg/3d至200mg/d。结果各组患者托哟酯总有效率分别为加用组82.7%,单药组初始剂量25mg/d组82.6%,初始剂量50mg/d,增量25mg/周组84.0%,初始剂量50mg/d,增量25mg/3d组70.8%,加用组和M1、M2组单用托吡酯总有效率比较无明显差异(P>0.05)。发生率比较高的副反应为感觉异常、食欲差和头痛。结论可单用托吡酯并给予较大初始剂量(50mg/d),以25mg/周速度增量治疗老年癫痫间。     

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。     

托吡酯治疗癫痫的临床疗效及安全性的观察

目的　观察及评价托吡酯对各型癫痫的临床疗效及安全性。方法　对 1998年 12月至2 0 0 0年 12月在我院确诊的 14 2例癫痫患者中的 93例采用托吡酯添加治疗、4 9例单药治疗 ,经 8周加量期和 12周稳定期观察后进行评价。结果　添加治疗组及单药治疗组总有效率分别为 79%和84 % ,完全控制率分别为 2 8%和 4 1%。成人有效剂量为 10 0～ 2 0 0mg/d ,儿童 3～ 5mg·kg-1·d-1。不良反应较轻 ,耐受性良好。结论　托吡酯是一种广谱、有效及安全的新型抗癫痫药 ,可作为一线抗癫痫药添加或单独使用。     

托吡酯添加治疗难治性癫癎的临床观察

目的　观察添加托吡酯对难治性癫的临床效果与副作用。方法　对 18例难治性癫患者 ,加用TPM后观察其发作频率并与加用前进行比较 ,计算总有效率。同时进行临床疗效和副作用观察。结果　病人加用托吡酯后总有效率为 5 0 % ,其中显效率达 2 2 2 % (3例未再发作 )。副反应以胃肠道反应及神经系统症状为主 ,发生率为 5 2 6%。结论　加用TPM治疗难治性癫安全有效。     

Topiramate or valproate in patients with juvenile myoclonic epilepsy: a randomized open-label comparison

Few randomized, controlled trials evaluating antiepileptic drug (AED) efficacy and tolerability have focused solely on patients with juvenile myoclonic epilepsy (JME). We conducted a pilot, randomized controlled trial comparing topiramate (N=19) and valproate (N=9) in adolescents/adults with JME to evaluate clinical response when these broad-spectrum agents are titrated to optimal effect. Rating scales were used to systematically assess tolerability. Among patients completing 26 weeks of treatment, 8 of 12 (67%) in the topiramate group and 4 of 7 (57%) in the valproate group were seizure-free during the 12-week maintenance period. Median daily dose was 250mg topiramate or 750mg valproate. Two (11%) topiramate-treated patients and one (11%) valproate-treated patient discontinued due to adverse events. Systemic toxicity scores, but not neurotoxicity scores, differed substantially between the two groups; greater systemic toxicity was associated with valproate. Our preliminary findings that topiramate may be an effective, well-tolerated alternative to valproate warrant validation in a double-blind trial.     

Efficacy and safety of topiramate in refractory epilepsy: a long-term prospective trial

The effects of topiramate in 15 patients with drug refractory partial epilepsy or Lennox-Gastaut syndrome were assessed in an open, add-on prospective study. After a follow-up of 14–21 months, six patients are still on topiramate (mean dosage 583 mg/day, range 400–800 mg/day), and nine have discontinued treatment because of adverse events (n=6), inefficacy (n=2) or poor compliance (n=1). Nine patients (69%) continued to have a 50% reduction in seizure frequency during the last two months of treatment, and one has been seizure-free for the last 19 months. The most common adverse events were somnolence, weight loss, mental slowing, fatigue, ataxia and irritability. Most of these events were reversible, but withdrawal of treatment was required in six cases as a result of ataxia (two patients), somnolence, metabolic acidosis, irritability or psychotic symptoms (one patient each). It is concluded that topiramate is a valuable agent for the long-term management of refractory epilepsy.

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Sommario Gli effetti di topiramato utilizzato in aggiunta alla terapia preesistente sono stati valutati nell'ambito di uno studio prospettico in aperto in 15 pazienti farmacoresistenti affetti da epilessia parziale o sindrome Lennox-Gastaut. Dopo un follow-up di 14–21 mesi, 6 pazienti sono tuttora in trattamento (posologia media di topiramato 583 mg/die, range 400–800 mg/die), mentre 9 hanno sospeso il farmaco a causa di eventi avversi (n=6), inefficacia (n=2) o scarsa compliance (n=1). Nove pazienti (69%) continuavano a presentare una riduzione di almeno il 50% della frequenza delle crisi durante gli ultimi 2 mesi di trattamento e un paziente è libero da crisi da 19 mesi. Gli eventi avversi più frequenti erano costituiti da sonnolenza, calo ponderale, rallentamento mentale, astenia, atassia e irritabilità. La maggior parte di questi eventi è risultata reversibile, ma in 6 pazienti si è resa necessaria la sospensione del trattamento a causa di atassia (2 casi), sonnolenza, acidosi metabolica, irritabilità e sintomi psicotici (1 caso ciascuno). Sulla base di questi dati, il topiramato può essere ritenuto un utile presidio nel trattamento a lungo termine dell'epilessia farmacoresistente.

     

妥泰加用治疗成人难治性部分性癫痫的疗效观察

目的：观察妥泰（TPM）加用治疗成人难治性部分性伴或不伴随继发身性发作（GTCS）的疗效,安全性及耐受性。方法：56例在不动原用抗癫痫药（AEDs)的基础上加用TPM治疗20周、前8周为加量期,后12周为维持治疗的稳定期,治疗前（基础期）记录好作频率,用药情况。体重等作为自身对照。TPM自25mg/d开始,逐渐加量,目标剂量为200mg/d,治疗及治疗结束各查基础AEDs血药浓度进行比较,治疗结束行全面疗效分析。结果：TPM加用治疗20周后,与基础期发作频率比较,64．29％患者发作频率降低≥50％;25．00％,患者发生频率降低≥75％＜100％;16．07％完全不发。不良反应轻至中度,但与合AEDs的多少有关。50％患者体重可有不同程度的下降。TPM对止痛民西平及丙戊酸钠血药浓度影响不大。结论：TMP是治疗难治性部分性伴或不伴继发GTCS的表效的药物。     

别嘌醇添加治疗难治性癫痫58例疗效观察

目的 :研究别嘌醇作为添加剂治疗难治性癫痫 (IE)的临床疗效与安全性。方法 :选自 1992～ 2 0 0 0年IE 5 8例 ,加用别嘌醇进行开放性自身对照研究 ,原服用的抗癫痫药 (AEDs)种类和剂量不变 ,以加用别嘌醇前 6个月的月发作频率为基线与治疗后 6个月的发作频率进行比较 ,常规计算发作改变百分率、有效率和脑电图好转率。结果 :发作改变百分数较加用前减少 6 7% (P <0 0 1) ,总有效率 5 8 6 2 % ,反应率为 5 0 % ,脑电图总有效率 6 8% (38/ 5 6 )。其临床疗效为全身强直———阵挛发作 (GTCs) >强直性发作 (Ts) >复杂部分性发作 (CPs) >单纯部分性发作 (SPs)。结论 :加用别嘌醇是治疗难治性癫痫的有效方法之一     

Prognostic factors affecting long-term retention of topiramate in patients with chronic epilepsy

PURPOSE: To determine the long-term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention. METHODS: All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan-Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression. RESULTS: Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy. CONCLUSIONS: A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy.     

Long-term efficacy and tolerability of topiramate as add-on therapy in refractory partial epilepsy: An observational study

Purpose:   To evaluate the long-term efficacy and tolerability of topiramate (TPM) as add-on therapy in patients with refractory partial epilepsy.
Methods:   This is a retrospective, single-center, long-term observational study. Patients fulfilling the criteria of medical intractability proposed by Berg et al. were entered into the study if they were newly prescribed TPM as add-on therapy between January 2000 and June 2002. The usual starting dosage of TPM was 50 mg/day and optimal-dose adjustments were made according to individual clinical responses. Efficacy and tolerability were analyzed every year during 5-year follow-up in the "intention-to-treat (ITT) population." Retention rate was estimated by Kaplan-Meyer analysis.
Results:   A total of 125 patients were included in the study and 107 patients (85.6%) were followed for 5 years. Retention rate was 87.2% at 1 year and 64% at 5 years. At the end of 5 years, the median seizure frequency reduction rate was 69.0% and responder rate was 43.2% in the ITT population. Cumulative seizure-free rate (SFR) was 30.4% and the terminal 1-year SFR was 12.8% in the ITT population (20.0% in completers) at 5-year follow-up. Adverse events (AEs) occurred in 39.2% of patients, including significant AEs leading to antiepileptic drug (AED) withdrawal in 14.4%. The most common AEs were anorexia (16.0%), weight loss (10.4%), and gastrointestinal symptoms (8.8%). Concomitant AEDs were reduced in 25.0% of the completers.
Discussion:   Low-dose and slow-dose escalation of TPM in add-on therapy for patients with refractory partial epilepsy is effective and well tolerated in long-term, individualized clinical practice.     

加用加巴喷丁治疗难治性癫痫的临床观察

目的观察加用加巴喷丁（ＧＢＰ）对难治性癫痫（ＩＥ）的临床效果与安全性。方法观察ＩＥ２０例，以加用ＧＢＰ前３个月的月均发作频率为基线，与治疗后１６周以上的月均发作频率进行比较，计算反应率，发作改变百分率（ＰＣＨ）和有效率，参照病人或家属病情日记。加用前和治疗中与结束前均定期进行临床和规定实验室检查。结果ＰＣＨ较加用前减少４７８％（Ｐ＜００１），有效率为１２／２０，其临床疗效单纯部分性发作（ＳＰＳ）＞全身强直阵挛性发作（ＧＴＣＳ）＞复杂部分性发作（ＣＰＳ），而对强直性发作（ＴＳ）无效。与其它传统抗痫药无明显交互作用。结论加用ＧＢＰ是治疗ＩＥ有效而安全的选择方法之一。     

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.