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。     

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.     

托吡酯对成人癫(癎)患者认知功能的影响

目的 探讨托吡酯(TPM)对成人癫(癎)患者认知功能的影响.方法 对采用TMP治疗的35例成人癫(癎)患者分别在治疗前和治疗3个月、6个月、12个月和24个月时进行简易精神状态检查(MMSE)量表和事件相关电位(ERP)P300检测.结果 与治疗前相比,治疗3个月时MMSE评分明显降低(P＜0.01);治疗3个月及6个月时P300潜伏期明昆延长(P＜0.01～0.05);12个月时恢复至治疗前水平.结论 TPM对癫(癎)患者认知功能的影响出现在加量期,并且是可逆的.     

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。     

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.     

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.     

托吡酯加用治疗难治性部分性癫Xian发作的临床研究

目的观察托吡酯加用治疗癫癎难治性部分性发作的疗效.方法32例难治性部分性发作或继发性全身性发作癫癎患者,病程1年以上,一直服用一种或两种基础抗癫癎药物每月仍有≥4次以上的发作.托吡酯采用加量法,加量期8周,目标剂量为200mg·d-1,观察12周后进入延长期.结果32例病人经过治疗后,发作100%消失者5例(15.62%),发作≤75%13例(40.62%),发作≤50%11例(34.37%),无改善2例(6.25%),因不良反应而中断1例(3.13%).结论托吡酯是一种非常有效的新型抗癫癎药物.     

Topiramate and psychiatric adverse events in patients with epilepsy

PURPOSE: The aim of this study was to determine the prevalence of psychiatric adverse events (PAEs) in patients with epilepsy treated with topiramate (TPM). Classification, relation to TPM dosing, and outcome were evaluated to identify a patient profile at risk of developing PAEs. METHODS: We evaluated the data of the first consecutive and prospectively collected patients in therapy with TPM. RESULTS: Follow-up information was available for 431 patients. PAEs occurred in 103 (23.9%) patients; M/F ratio, 55:48; mean age (+/-SD), 36.5 +/- 11.2. In 46 (10.7%) patients, an affective disorder developed; in 16 (3.7%), a psychotic disorder; in 24 (5.6%), aggressive behavior with or without irritability; in 17 (3.9%), other behavior abnormalities such as agitated behavior, anger/hostility behavior, or anxiety. High starting dose and rapid titration schedule were relevant for the development of PAEs. Family psychiatric history and family history of epilepsy, personal history of febrile convulsions, psychiatric history, and presence of tonic-atonic seizures were found to be significant risk factors. Low seizure frequency before starting TPM and TPM/lamotrigine coadministration had a protective effect for PAEs. CONCLUSIONS: We found that PAEs associated with TPM were related to the titration schedule of the drug and that a unique patient profile is suggested by the clinical history.     

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.     

The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy

Purpose: To investigate the effect of topiramate on bone mass and metabolism in premenopausal women with epilepsy. Methods: Thirty‐six women on long‐term (at least 1 year) topiramate monotherapy were compared with 36 women taking carbamazepine, 32 women taking valproate, and 36 age‐ and sex‐matched controls. Subjects completed bone mineral density (BMD) studies. Serum was analyzed for indices of bone metabolism. Key Findings: BMD Z‐scores, and serum 25‐hydroxyvitamin D and 1alpha,25‐dihydroxyvitamin D₃ concentrations did not differ among the groups. Serum calcium concentrations were significantly lower in patients receiving topiramate than in those receiving valproate, and in patients receiving carbamazepine than in those receiving valproate and controls. Patients taking topiramate had lower levels of parathyroid hormone compared with controls and those taking carbamazepine or valproate. Patients receiving topiramate had higher levels of bone‐specific alkaline phosphatase and osteocalcin when compared with controls and higher levels of C‐terminal telopeptide of type 1 collagen when compared with those taking carbamazepine or valproate. Patients receiving carbamazepine had higher levels of bone‐specific alkaline phosphatase compared with controls and those receiving valproate. Serum bicarbonate concentrations were significantly lower in patients receiving topiramate than in the other groups. Significance: Our results demonstrate that use of topiramate is associated with lower parathyroid hormone and bicarbonate concentrations along with mild hypocalcemia and increased bone turnover, which suggests that topiramate may have long‐term effects on bone.     

托吡酯单用及添加治疗癫痫302例临床分析

目的　观察托吡酯添加和单药治疗癫痫的临床疗效及不良反应 ,并探讨单药治疗的理想给药模式。方法　入组患者分为 3组 ,A组 10 2例采用托吡酯添加治疗 ,B组 2 0 0例采用托吡酯单药治疗 ,按初始剂量及加量速度不同 B组又分为 B1组、B2组。B1组 10 5例 ,妥泰初始剂量 2 5 mg/ d,增量 2 5 m g/ w至 2 0 0 m g/ d;B2组 95例 ,妥泰初始剂量 5 0 mg/ d,增量 5 0 m g/ w至 2 0 0 m g/ d。维持治疗 12周。记录发作情况及不良反应。结果　 A组总有效率及控制率分别为 6 0 .8%、2 4 .5 % ,B组总有效率及控制率为 76 .8%、4 1.5 % ,两组疗效差异有显著性意义 (P<0 .0 5 )。 B1组总有效率及控制率分别为 77.9%、4 1.9% ,B2组总有效率及控制率分别为 75 .8%、4 0 .0 % ,两组疗效差异无显著性意义 (P>0 .0 5 )。托吡酯对各型部分性发作及强直 -阵挛性发作的疗效差异无显著性意义 (P>0 .0 5 )。B2组不良反应高于 B1组 ,差异有显著性意义 (P<0 .0 5 )。结论　托吡酯添加及单药治疗癫痫具有良好的疗效 ,对发作频率较低的患者宜选用小剂量起始缓慢加量的治疗方法 ,对发作频率较高的患者可考虑予较大起始剂量并以较快速度加量以尽快控制发作     

Topiramate pharmacokinetics in children with epilepsy aged from 6 months to 4 years

PURPOSE: To study the pharmacokinetics of topiramate (TPM) at steady state in children younger than 4 years comedicated with other antiepileptic drugs (AEDs). METHODS: Twenty-two children aged 6 months to 4 years with pharmacoresistant partial or generalized epilepsy were enrolled in an open-label prospective study. Children were assigned to different groups according to comedication with enzyme-inducing AEDs (n = 8), valproic acid (VPA) (n = 6), or other AEDs not known to affect drug metabolism (neutral AEDs, n = 7). One child was receiving treatment with both enzyme-inducing AEDs and VPA. After dose titration, blood samples were collected at steady state just before and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 h after the morning dose of TPM. Pharmacokinetic parameters were determined by a noncompartmental method. RESULTS: TPM apparent oral clearance (CL/F) was significantly higher in children taking enzyme-inducing AEDs (85.4 +/- 34.0 ml/h/kg) than in those receiving VPA (49.6 +/- 13.6 ml/h/kg) or neutral AEDs (46.5 +/- 12.8 ml/h/kg). Conversely, dose-normalized areas under the plasma TPM concentration curves (0-12 h) were significantly lower in enzyme-induced patients than in patients receiving VPA or other AEDs. CONCLUSIONS: Compared with children not receiving enzyme inducers, children younger than 4 years who receive concomitant enzyme-inducing AEDs need higher doses (milligrams per kilogram) to achieve comparable plasma TPM concentrations.     

妥泰单药治疗部分性癫痫的疗效观察

目的 观察妥泰单药治疗部分性癫痫病人的疗效及安全性。方法 对30例部分性癫痫患者应用妥泰单药治疗20周,于治疗前观察并记录基础发作频率,剂量从25mg/d开始,每周增加25mg,共8周,达有效剂量或200mg/d后维持治疗12周,并观察癫痫发作频率变化及不良反应等。结果 发作完全控制16例（53．3％）,发作减少≥75％6例（20％）,发作减少≥50％2例（6．7％）,发作减少＜50％6例（20％）。病程短者治疗效果较好。首次接受抗癫痫药物治疗者发作完全控制比例明显高于经治过的病人。治疗过程中无严重不良反应。结论 妥泰单药治疗对控制单纯部分发作及复杂部分性发作均有良好的效果,且耐受性、安全性好。     

托吡酯对癫痫大鼠海马神经细胞凋亡的保护作用

目的　探讨托吡酯对癫痫发作大鼠海马神经元凋亡的影响及其可能的机制。方法　采用戊四氮致痫模型 ,大鼠癫痫发作后连续给予托吡酯 80mg/ (kg·d)和 4 0mg/ (kg·d) ) ,共 14d。以TUNEL方法标记DNA片段 ,原位检测海马CA1和CA3区的神经细胞凋亡。结果　各组大鼠海马CA1、CA3区均出现TUNEL阳性细胞。对照组 ,海马CA1、CA3区TUNEL阳性细胞数分别为 (35 .83± 4 .5 8)个和(36 .83± 3.87)个 ;4 0mg/ (kg·d)托吡酯组分别为 (31.5 2± 3.4 3)个和 (32 .35±4 .6 9)个 ;80mg/ (kg·d)托吡酯组为 (2 1.17± 3.0 6 )个和 (2 1.16± 3.87)个。 80mg/ (kg·d)托吡酯组与对照组比较存在显著差异(P<0 .0 0 1) ,4 0mg/ (kg·d)托吡酯组TPM组与对照组相比无显著差异 (P >0 .0 5 )。结论　TPM对癫痫发作后神经元凋亡具有一定的保护作用     

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 and lamotrigine pharmacokinetics during repetitive monotherapy and combination therapy in epilepsy patients

PURPOSE: To determine at steady state (in the same group of patients): (a) the pharmacokinetics (PK) of lamotrigine (LTG) with LTG monotherapy, (b) the PK of LTG concomitantly administered with topiramate (TPM) at three escalating TPM doses (100, 200, and 400 mg/day), (c) the PK of TPM at three escalating TPM doses while receiving fixed-dose LTG therapy, and (d) the PK of TPM with TPM monotherapy. METHODS: This was an open-label, sequential, single-group, dose-escalating PK study in which 13 patients with epilepsy not optimally controlled with LTG received stable-dose LTG monotherapy for 2 weeks, followed by stable-dose LTG therapy combined with escalating doses of TPM for 相似文献