托吡酯单药治疗癫癎的临床观察

目的观察托吡酯(TPM)单药治疗癫癎的临床疗效和不良反应.方法应用TPM治疗64例癫癎患者,平均日剂量为138 mg,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.10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长期单药治疗癫癎疗效明显,耐受性好,较为安全.     

托吡酯治疗癫癎的长期疗效观察

目的观察托吡酯治疗不同类型癫癎的长期疗效及安全性.方法采用开放性试验的方法,给予115例不同类型癫癎患者托吡酯单药或添加治疗,6个月后进行疗效评定,1年和2年时计算控制率和托吡酯保留率,记录不良反应.结果 (1) 6个月时总有效率单药治疗组为83.9%,添加治疗组为66.1%,对各型癫癎均有一定疗效,各组间发作控制率和总有效率比较差异无显著性;(2)稳定期儿童组有效剂量为(105.72±48.28) mg/d,成人组为(176.36±62.81) mg/d;(3)控制率1年为40.0%,2年为28.7%;保留率1年为67.8%,2年为46.1%;(4)34例(29.6%)出现不良反应,为轻、中度的中枢神经系统症状以及厌食和体质量减轻.结论托吡酯是较好的广谱抗癫癎药物,长期应用仍有较好的疗效和安全性.     

托吡酯治疗老年继发性癫癎患者的临床观察

目的观察及评价托吡酯对老年性继发性癫癎患者的临床疗效和安全性。方法收集2007年1月~2008年12月神经内科门诊患者中60岁以上老年继发性癫癎患者40例,只给予托吡酯治疗,而且未服用其它任何抗癫癎药物,于3、6、12个月进行随访,评价托吡酯的临床疗效和安全性。结果 40例患者的有效率均在80%以上。无1例患者发生重度不良反应。结论托吡酯治疗老年继发性癫癎患者有效且安全。     

托吡酯治疗难治性癫癎的疗效观察

目的　评价托吡酯 (TMP)添加治疗难治性癫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　采取开放性试验的方法对 80例难治性癫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总有效率5 8 6% ,对单纯部分性发作有效率 66 7% ,复杂部分性发作 2 5 % ,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有效 ,但要注意用药量的个体化。     

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。     

奥卡西平和托吡酯单药治疗癫(癎)的临床观察

目的 比较奥卡西平(OXC)、托吡酯(TPM)单药治疗癫(癎)的疗效和安全性.方法 癫(癎)门诊病人78例,随机分为OXC组和TPM组,单药治疗,观察24周.结果 TPM组38例,有效率76.3%、显效率63.1%,控制率(无发作)44.7%.OXC组40例,有效率75%、显效率62.5%,控制率(无发作)45%.经统计学处理两组疗效没有显著性差异(P=0.89＞0.05).TPM组有效剂量中位值为100 mg/d,OXC组为600 mg/d.TPM组不良反应8例,OXC组6例,两组不良反应发生率没有显著性差异(P=0.49＞0.05).TPM组不良反应常见胃纳差、记忆力减退、头部不适、嗜睡,其中2例分别因为手足麻木及胃纳差、体重减轻而退出.OXC组不良反应常见乏力、头昏、头疼、嗜睡、恶心、皮疹等,没有因为不良反应而退出.结论 TPM和OXC单药治疗癫(癎)疗效明显,不良反应轻,耐受性好,安全性高.二者疗效、不良反应没有显著性差异.     

应用托吡酯治疗小儿难治性癫癎的临床研究

目的观察托吡酯治疗小儿难治性癫癎疗效、用药方法及副反应.方法采用开放性方法对31例小儿难治性癫癎患者进行单用或加用托吡酯治疗.观察其疗效及副反应.结果托吡酯治疗小儿难治性癫癎总有效率67.7%.38.7%患儿停止发作,对部分性发作疗效较好.其他类型发作亦有一定疗效.平均有效剂量为(4.0±1.8)mg@kg-1@d.副反应主要为体重减轻(16例,56.6%),神经系统症状,少汗或无汗,皮疹等,结论托吡酯对小儿难治性癫癎有良好疗效.     

单用不同剂量托吡酯与奥卡西平治疗儿科癫(癎)的疗效比较

目的 观察单用不同剂量托吡酯及奥卡西平治疗儿科癫患儿的临床疗效和不良反应.探讨单用托吡酯更安全、更有效的给药方法.方法 儿科癫患儿120例,分为奥卡西平组31例,服用奥卡西平从8～10mg/(kg·d)开始,再逐渐增量到10～30mg/(kg·d),2次/d服用;单用托吡酯组,89例患儿按服药剂量不同又分为低剂量组47例托1组从0.625mg/(kg·d)开始增加至4mg/(kg·d)为止;高剂量组42例托2组从1.5mg/(kg·d)开始,逐增至8mg/(kg·d)为止.结果 托1组总有效率81%,托2组总有效率74%;奥卡西平组总有效率77%,3组比较无显著差异(P＞0.05).托2组不良反应发生率(57%)高于托1组(34%)(P＜0.05).托吡酯组主要不良反应为胃纳差、头痛、感觉异常、嗜睡和体质量减轻.结论 单用较小剂量托吡酯治疗儿科癫发作,疗效好,不良反应少.     

托吡酯治疗难治性癫癎32例分析

目的观察托吡酯治疗难治性癫痫的疗效与安全性。方法对32例难治性癫痫患者加用托吡酯治疗进行临床观察研究。结果15例患者发作频度减少≥50％,8例患者发作频度减少到26％～49％,疗效较佳;各种类型癫痫之间发作减少差异不显著;与不同抗癫痫药物合用疗效无差异。结论托吡酯是一种有效的广谱抗癫痫药,能与常用抗癫痫药合用。     

托吡酯加用及单用治疗老年癫癎发作的临床观察

目的观察加用及单用托吡酯二种方式治疗老年癫癎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.方法老年癫癎患者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50mg/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癎.     

托吡酯与卡马西平对成年癫痫患者甲状腺激素的影响

目的探讨托吡酯（TPM）及卡马西平（CBZ）对成年癫痫患者甲状腺激素水平的影响。方法选择新确诊的100例成年癫痫患者（50例服用TPM、50例服用CBZ）为试验组,用化学发光法测定用药前甲状腺激素水平并与40例成年健康对照进行比较；再经TPM、CBZ单药治疗3、6个月及1年后检测血中甲状腺激素水平,并与治疗前比较。结果未经治疗的癫痫患者甲状腺激素水平与正常对照组比较无显著性差异（P＞0．05）；与治疗前相比,CBZ治疗3个月、6个月及1年后的游离T4（FT4）、三碘甲状腺原氨酸（TT3）及CBZ治疗6个月及1年后的甲状腺素（TT4）显著降低（P＜0．05）,而CBZ治疗3个月的TT4与服用CBZ后各时点的游离T3（FT3）、促甲状腺素（TSH）无显著性变化（P＞0．05）；经TPM治疗后的不同时段的甲状腺激素水平与治疗前比较均无显著性差异（P＞0．05）。结论CBZ治疗可造成成年癫痫患者甲状腺激素水平的降低。癫痫本身及TPM治疗并不引起成年患者甲状腺激素水平的改变,表明TPM治疗对成年癫痫患者的甲状腺功能更安全。     

卡马西平 托吡酯与丙戊酸钠治疗脑炎继发癫痫的疗效分析

目的观察卡马西平、托吡酯与丙戊酸钠治疗脑炎继发癫痫的疗效。方法选取60例脑炎继发癫痫患者为研究对象,随机分为A、B、C 3组,每组20例,A组给予卡马西平治疗,B组给予丙戊酸钠治疗,C组给予托吡酯治疗。对3组疗效进行评价;对3组患者治疗期间不良反应的发生情况进行观察。结果 3组临床有效率分别为70%、70%和75%,差异无统计学有意义(P0.05),且3组各项疗效评价结果差异均无统计学意义(P0.05);3组治疗期间不良反应的发生率分别为55%、45%和15%,A组或B组不良反应发生率显著高于C组(P0.05),A组皮疹发生率显著高于B组与C组(P0.05)。结论卡马西平、丙戊酸钠、托吡酯治疗脑炎继发癫痫的疗效基本相当,但托吡酯的不良反应较少,有助于提高患者的依从性。     

托吡酯单药治疗各型癫癎的临床研究

目的观察托吡酯单药治疗成人和儿童各型癫癎的临床效果与安全性.方法用开放性试验的方法对34例癫癎患者进行了添加转单药以及首诊单药的托吡酯治疗;以加用托吡酯前3个月的月均发作频率为基准,与单用或转换单用托吡酯进入稳定期后3个月的月均发作频率进行比较,按常规计算发作减少百分比的中位值和有效率百分比.结果托吡酯无论在添加转单药还是单药的治疗上均有明显疗效,且抗谱广,可用于单纯部分性发作有或全面性发作、复杂部分性发作有或全面性发作、婴儿痉挛症,无耐药现象.14岁以上者托吡酯单药治疗的剂量明显低于添加治疗组.托吡酯的副反应以中枢神经系统最常见,但导致治疗中断的副反应尚未见到.结论托吡酯是一个广谱抗癫癎药,疗效肯定,无耐药性,无严重副反应,可用于单药治疗.     

Time course of adverse events in patients with localization-related epilepsy receiving topiramate added to carbamazepine

PURPOSE: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. METHODS: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (> or =5% incidence) AEs were calculated for patients completing the 12-week study. RESULTS: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. CONCLUSIONS: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy.     

The effects on cognitive function and behavioral problems of topiramate compared to carbamazepine as monotherapy for children with benign rolandic epilepsy

PURPOSE: To evaluate the cognitive and behavioral effects of topiramate (TPM) versus carbamazepine (CBZ) using efficacious doses of each drug as monotherapy for children with benign rolandic epilepsy. METHODS: A multicenter, randomized, open-label, observer-blinded, parallel-group clinical trial was conducted. TPM was introduced at a dose of 12.5 mg/day with the minimum target dose of 50 mg/day in patients <30 kg and 75 mg/day in patients >30 kg over 4 weeks. CBZ was started at a dose of 10 mg/kg/day with the minimum target dose of 20 mg/kg/day over 4 weeks. Additional individual escalation was allowed up to a maximum target dose. The primary study end point was change on a neuropsychological test battery after 28 weeks of treatment. RESULTS: Neuropsychological data were available for 88 patients (45 patients for TPM and 43 patients for CBZ). Of the cognitive variables measured, arithmetic showed significant worsening in TPM (p = 0.037). An additional test, for maze, also showed a significantly greater improvement for CBZ (p = 0.026). Of behavioral variables, no significant changes were found but the scores had a negative trend for the TPM. When 30 patients on the minimum target dose for TPM were compared to 40 patients treated with minimum target CBZ, there was no significant worsening of cognitive and behavioral effects in the TPM. CONCLUSION: The pattern of neuropsychometric changes with TPM seemed to be slightly worse overall than CBZ. However, outcome with the minimum target dose did not differ significantly in comparisons between the treatment groups.     

托吡酯对癫痫大鼠认知功能及海马组织中NCAM的mRNA表达影响

目的研究托吡酯（TPM）对癫痫大鼠认知功能的影响以及使用TPM后大鼠海马组织中神经细胞粘附分子（NCAM）的mRNA表达变化。方法将大鼠随机分成生理盐水（NS）组、癫痫（EP）组、癫痫＋托吡酯治疗1周（TPM1周）组和癫痫＋托吡酯治疗4周（TPM4周）组,建立匹罗卡品诱导癫痫大鼠模型和TPM干预模型,观察大鼠的行为学改变,通过Morris水迷宫实验测试大鼠的学习记忆能力,并通过Real—TimePCR检测大鼠海马组织中NCAM的mRNA表达水平。结果EP组大鼠的逃避潜伏期大于NS组,原平台象限游泳时间百分比小于NS组,海马NCAM的mRNA表达水平高于NS组（P〈0．01）;TPM1周组和TPM4周组大鼠的逃避潜伏期大于EP组,原平台象限游泳时间百分比小于EP组,海马NCAM的mRNA表达水平低于EP组（P〈0.01）;TPM4周组大鼠的逃避潜伏期大于TPM1周组,原平台象限游泳时间百分比小于TPM1周组,海马NCAM的mRNA表达水平低于TPMI周组（P〈0.05）。结论大鼠产生癫痫持续状态后认知功能明显下降,海马NCAM的mRNA表达上调;使用大剂量TPM短期治疗后其认知功能进一步下降,海马NCAM的mRNA表达受抑,且下降与受抑程度与TPM的持续使用时间有关。     

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.     

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.

     

传统抗癫疒间药物与托吡酯对成年癫疒间患者生活质量影响的对比研究

目的 探讨传统抗癫癎药物(AEDs)与托吡酯(TPM)对成年癫癎患者生活质量(QOL)的影响。方法 102例临床确诊的成年癫癎患者随机分为AEDs组和TPM组,井用QOL IE-30表对102例癫癎患者和62名正常人(对照组)进行评定。结果 AEDs组较对照组QOL明显降低(P<0.05),表现惧怕发作,对日常生活不满意,情绪差,精力不足,认知功能下降,对长期服用抗癫癎药物的顾虑较多,社交、工作受限等;而TPM组的QOL虽然低于对照组(P<0.05),但在前5项的评分中明显高于AEDs组(P<0.05)。TPM组的发作频率明显低于AEDs组(P<0.05)。发作频率对癫癎患者QOL的影响较大,癫癎发作越频繁,QOL越差。结论 成年癫癎患者的QOL较正常人显著降低,TPM能提高癫癎患者的QOL,其改善QOL的作用主要是通过控制发作实现的。因此,合适的药物控制癎性发作是提高癫癎患者QOL的关键。     

托吡酯单药及添加治疗癫痫疗效的随访观察

目的观察托吡酯单药及添加治疗不同类型癫痫的长期临床疗效。方法对服药大于2年的95例癫痫患者给予托吡酯单药和添加治疗;分别于服药6个月、1年、2年时进行随访。评定其控制率、托吡酯保留率,以及不良反应。结果服药6个月时,不同发作类型患者中以简单部分性发作(SPS)及全面强直阵挛性发作(GTCS)患者的控制率最好,分别为58.8%和52.8%;单药治疗组控制率(63.8%)显著高于添加组(27.0%);单药治疗组1年(50.0%)及2年时(41.7%)的控制率显著高于添加组(23.8%,20.0%)(均P<0.01);单药治疗组1年(68.5%)及2年(62.1%)的保留率显著高于添加组(56.8%,40.5%)(均P<0.01);本组的不良反应依次为厌食、体重减轻、无汗、反应迟钝、肢体麻木、记忆力下降、注意力不集中等。结论托吡酯对各类型癫痫均有明显的疗效,其中以SPS和GTCS最显著;其短期、长期的控制率均较好。