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.     

托吡酯治疗各型癫癎的疗效与安全性观察

目的 观察托吡酯（TPM)对成人和儿童各型癫痫的临床效果与安全性。方法 用开放性试验方法对100例癫痫患者进行了添加、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个月的平均月发作频率为基准，与用托吡酯进入稳定期后的月平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 托吡酯无论在添加治疗、添加转单药以及单药治疗上均有明显疗效。添加组70％患者的发作减少，添加转单药组发作减少者占78％，而单药组发作减少者占86％。其抗癫痫谱广，可用于单纯部分性发作伴或不伴全面性发作、复杂部分性发作伴或不伴全面性发作、婴儿痉挛以及Lennox—Gastaut综合征。托吡酯的不良反应以中枢神经系统最常见，但导致治疗中断的不良反应少见，本组仅3例因不良反应而中断治疗。结论 托吡酯是广谱抗癫痫药，疗效肯定，无耐药性，无严重不良反应，即既可用于添加治疗也可作为单药治疗。     

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。     

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.     

托吡酯治疗躁狂患者的疗效分析

目的：探讨托吡酯躁狂患者的疗效。方法：对59例躁狂、轻躁狂和混合躁狂发作的患者单用或合用托吡酯治疗6周，评价疗效及副作用。结果：托吡酯治疗躁狂患者的有效率为59.3%；合用比单用（65.9%比40%）疗效更好；托吡酯治疗比相Ⅱ型比双相I型、混合型、未分型疗效更好（81.8%比54.2%、60.0%、33.3%）。不良反应有轻微静坐不能、震颤、嗜睡及胃肠道反应。结论：建议托吡酯治疗躁狂患者时以合用为主，对双相Ⅱ型患者更为有利。     

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。     

托吡酯长期治疗儿童癫(癎)部分性发作疗效及耐受性的观察

目的观察托吡酯长期治疗儿童癫(癎)部分性发作的疗效、耐受性及安全性.方法对86例癫(癎)部分性发作的患儿给予托吡酯加用或单药治疗,起始剂量为0.5～1.0 mg/(kg·d),分2次口服,每周增加0.5～1.0 mg/(kg·d),经过8周加量期及18个月稳定期,观察其疗效、耐受性及安全性.结果 86例患儿完成加量期后,总有效率为61.6%,控制率为37.2%.稳定期6、12及18个月时总有效率分别为68.6%、81.9%及86.4%,控制率分别为46.5%、59.0%及60.5%,稳定期12及18个月时总有效率及控制率与加量期比较差异有显著性(均P<0.05).不良反应多发生在治疗初期,为一过性轻～中度嗜睡、厌食等.在稳定期18个月时仍有78例(90.7%)坚持服用托吡酯.结论托吡酯对儿童癫(癎)部分性发作的长期治疗,具有较高的疗效及较好的安全性与耐受性.     

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。     

托吡酯长期治疗儿童癫痫部分性发作疗效及耐受性的观察

目的观察托吡酯长期治疗儿童癫(癎)部分性发作的疗效、耐受性及安全性.方法对86例癫(癎)部分性发作的患儿给予托吡酯加用或单药治疗,起始剂量为0.5～1.0 mg/(kg·d),分2次口服,每周增加0.5～1.0 mg/(kg·d),经过8周加量期及18个月稳定期,观察其疗效、耐受性及安全性.结果 86例患儿完成加量期后,总有效率为61.6%,控制率为37.2%.稳定期6、12及18个月时总有效率分别为68.6%、81.9%及86.4%,控制率分别为46.5%、59.0%及60.5%,稳定期12及18个月时总有效率及控制率与加量期比较差异有显著性(均P<0.05).不良反应多发生在治疗初期,为一过性轻～中度嗜睡、厌食等.在稳定期18个月时仍有78例(90.7%)坚持服用托吡酯.结论托吡酯对儿童癫(癎)部分性发作的长期治疗,具有较高的疗效及较好的安全性与耐受性.     

Topiramate slow dose titration: improved efficacy and tolerability

Topiramate is an effective treatment for several types of seizures. The aim of this study is to assess the efficacy and tolerability of slow topiramate dose titration as add-on therapy in childhood epilepsy. This investigation is a prospective open-label, single-center, add-on study in 22 children with a diagnosis of refractory epilepsy. Topiramate (dose 0.5-2 mg/kg/day) was titrated at 2-week intervals up to the recommended dose of 6-12 mg/kg/day. Seizure frequency rate reduction was significant, declining from 23 +/- 5.1 seizures/week (mean +/- S.E.M.) at baseline phase to 3.5 +/- 1.2 seizures/week at the end of the 16-week stabilization phase (P < 0.001). After 16 weeks of stabilization, 19 patients (86%) had more than 50% seizure reduction. Seven patients (31%) were 100% seizure-free. Two patients (9%) manifested no improvement; only one patient (5%) did not tolerate the added drug and discontinued topiramate. One patient manifested severe side effects, whereas 21 patients experienced mild to moderate side effects mostly represented by somnolence, nervousness, and anorexia with or without weight loss. We conclude that slow dose titration improves efficacy and tolerability of topiramate as add-on therapy in the treatment in refractory epilepsy.     

Clinical experience with open-label topiramate use in infants younger than 2 years of age

To assess the efficacy, safety, and tolerability of topiramate in infants younger than 24 months of age, we conducted an open-label, multicenter chart review study of infants who received topiramate. Twenty-eight patients were evaluated. All had refractory epilepsy. The mean age of seizure onset was 3.8 months (range 0-10 months). Refractory infantile spasms were the most common epilepsy syndrome. Among infants without infantile spasms, complex partial seizures were the prominent seizure type in eight, followed by simple partial seizures in six. Topiramate was prescribed as add-on therapy in 25 cases and a s monotherapy in 3 cases. Seven of the eight infantile spasms cases improved on topiramate therapy, attaining topiramate monotherapy in three infants. Half of the infants with other seizure types responded to topiramate. The average treatment duration among topiramate responders was 11 months. Topiramate was prescribed after a mean of 3.3 antiepilepsy drugs had been used in these infants. In no case was topiramate the first prescribed antiepilepsy drug. Adverse effects occurred only in five patients, leading to topiramate discontinuation in two patients. Topiramate was efficacious and well tolerated in infants younger than 24 months of age with refractory epilepsy. Prospective data are needed to corroborate this observation.     

Topiramate in add-on therapy: results from an open-label, observational study.

An open-label, observational prospective study assessed the effectiveness of topiramate (TPM) as add-on therapy. A total of 450 patients aged 12 and above with a diagnosis of epilepsy and at least one epileptic seizure during the 12-week retrospective baseline were to be documented. After baseline evaluation, topiramate was added. Ninety-five percent of patients had at least one baseline AED, most commonly Carbamazepine (53%) or Valproate (34%). In 5% TPM was started in monotherapy. Topiramate dose titration and target dose was determined by clinical response and side effect profile. Patients were intended to be followed for a total of 1 year which included 6 visits during which seizure frequency, adverse events, weight as well as clinical global impression were recorded. During the 12 weeks retrospective baseline, a median of 2.8 seizures per month were recorded which reduced significantly to 0.7 per month during the complete treatment phase (p < 0.0001). Seventy-two percent of patients had a > or =50% seizure reduction. Ten percent of patients were seizure free during the study. The most commonly reported adverse events were difficulties with memory (4.2%), somnolence (3.6%), and dizziness (2.7%). Overall, topiramate was well tolerated, and only 5% of patients discontinued treatment due to an adverse event. Retention in the study was higher than previously reported during randomized, dose controlled studies and is likely due to individualized doses as well as slower titration used.     

Use of topiramate in childhood generalized seizure disorders

Topiramate is a sulfamate derivative of the naturally occurring monosaccharide D-fructose. It was initially approved in the United States as adjunctive therapy for partial seizures in 1997. However, there is increasing evidence that it is effective in the treatment of generalized seizures and epilepsy syndromes. Initially, open-label studies using topiramate as add-on therapy in children with refractory generalized seizure types were performed. These showed improvement in patients with the following generalized seizure types: typical and atypical absence, atonic, myoclonic, generalized tonic-clonic, and juvenile myoclonic epilepsy. Double-blind, placebo-controlled multicentered studies in patients with refractory primary generalized tonic-clonic seizures and epilepsy syndromes were performed. The median reduction in seizure frequency for primary generalized tonic-clonic seizures was 56.7% for topiramate and 9% for placebo. Additionally, 13.6% of topiramate-treated patients were primary generalized tonic-clonic seizure free for the study period. In the topiramate-treated juvenile myoclonic epilepsy patients, primary generalized tonic-clonic seizures were reduced > 50% in 73% of patients. Open-label extension showed that primary generalized tonic-clonic seizures were reduced >50% in 63% of topiramate-treated patients for > or = 6 months, and 16% were primary generalized tonic-clonic seizure free > or = 6 months. Accumulating evidence suggests that topiramate has a broad spectrum of antiepileptic effect. Moreover, life-threatening organ toxicity has not been attributed to topiramate. Topiramate is an effective treatment for refractory generalized seizure types and epilepsy syndromes encountered in children.     

A randomized, double-blind, placebo-controlled trial of topiramate in adults with epilepsy and intellectual disability: impact on seizures, severity, and quality of life

This randomized, double-blind, placebo-controlled UK trial evaluated the effect of topiramate as add-on therapy on seizure frequency, seizure severity, and quality of life in patients with epilepsy and intellectual disability. There were three phases: 4 weeks baseline, 18 weeks titration to 200-400 mg topiramate/day (adults) or 5-9 mg/kg/day (children), 12 weeks maintenance. Recruitment was low (88/120); analyses were underpowered. Seizure frequency varied enormously (median 17.7, maximum 1706.2). There was no significant difference in reduction in mean total seizure frequency or number of responders between the groups. Topiramate reduced seizure frequency by >30% from baseline (placebo 1%); post hoc analyses showed a trend toward significance (R ratio, P=0.052). There were no significant differences between the groups with respect to mean seizure severity or other outcome measures. Topiramate was generally well tolerated; body weight (P=0.015) and systolic blood pressure (P=0.043) were reduced. The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects, and was potentially advantageous to physical well-being.     

The efficacy and side effects of topiramate on refractory epilepsy in infants and young children: a multi-center clinical trial.

OBJECTIVES: This study has been conducted to assess the efficacy and safety of topiramate in refractory epilepsies in infants and young children. METHODS: A prospective clinical trial was performed in three tertiary care hospitals, on 47 children aged 6-60 months with refractory epilepsy. Topiramate was added to at least two baseline anti-epileptic drugs. The efficacy was rated according to seizure type, frequency and duration. RESULTS: Children with refractory epilepsy were classified according to their clinical, neuro-imaging, and neurophysiological profile into infantile spasms (IS) (9 cases, 19%), Lennox-Gastaut syndrome (LGS) (25 cases, 53%) and other epilepsies (13 cases, 28%). Children were also classified into cryptogenic and symptomatic epilepsy. Topiramate was introduced as add-on therapy in a daily dose of 1 mg/kg/day for 2 weeks, followed by increments of 1-3 mg/kg/day at 2-week intervals, up to a maximum of 10 mg/kg/day. After a minimum treatment period of 6 months, 28 (60%) of the children had a satisfactory response (completely seizure free, or more than a 50% seizure reduction). The remaining 19 children (40%) had an unsatisfactory response (50% or less reduction in seizure frequency, no change or increased seizure frequency). Topiramate appeared to be equally effective in infantile spasms, Lennox-Gastaut syndrome and children with other types of epilepsy, with no significant difference between those with a satisfactory and an unsatisfactory response (p=0.089). There was also no significant difference in response between patients with cryptogenic and symptomatic epilepsy (p=0.360). Mild to moderate adverse effects, mainly somnolence, anorexia and nervousness, were present in 25 (53%) of children. One of the children developed hypothyroidism. CONCLUSION: Although the long term safety and possible adverse effects of topiramate have not been fully established in infants and young children, this study has shown that it is a useful option for children with frequent seizures unresponsive to standard anti-epileptic drugs.     

Topiramate monotherapy as broad-spectrum antiepileptic drug in a naturalistic clinical setting.

Topiramate was assessed in an open-label trial as broad-spectrum antiepileptic monotherapy, independently from the epilepsy type or syndrome. Adults and children aged 2 years and older, who were diagnosed with epilepsy within the last 5 years, treatment-naive or failing prior treatment with one antiepileptic drug (AED), received individually adjusted doses of topiramate, after escalation to 100mg/day over 4 weeks (maximum 400mg/day) or 3mg/kg/day over 6 weeks (maximum 9 mg/kg/day), respectively. Patients were followed for >or=7 months and optionally up to a maximum of 13 months. Data were analysed for all patients (n=692), as well as for focal (n=421) and generalized epilepsies (n=148). The median topiramate dose used was 125 mg/day in adults and 3.3mg/kg/day in children (or=50% reduction in mean monthly seizure frequency. Patients with focal and generalized epilepsies alike responded to treatment (73.9 and 83.8% with at least 50% seizure reduction): 39.4% of patients with focal epilepsy and 61.5% of those with generalized epilepsy were seizure-free. The mean monthly seizure frequency was significantly reduced versus baseline at all visits (p<0.001). Similar response rates were obtained from the 237 patients completing the 1-year observation period. During the mandatory 7-month period of study, 8.8% of patients reported insufficient tolerability as a reason for dropout. The most frequent adverse event was paraesthesia. Our results support findings that emerge from controlled studies that topiramate is effective and well tolerated when used as initial or second monotherapy. They also suggest that in a naturalistic setting, overall good retention on treatment and seizure freedom are observed at low doses in a broad spectrum of epilepsies.     

Evidence for a rapid action of levetiracetam compared to topiramate in refractory partial epilepsy.

The objective of this observational study was to compare the efficacy of levetiracetam and topiramate during the first 15 days of add-on treatment in adults with refractory partial epilepsy. Two cohorts of patients with > or =3 simple or complex partial seizures with or without secondary generalisation per month over an 8-week baseline period received levetiracetam or topiramate in two distinct phases, in addition to standard antiepileptic treatment. During the first 15 days of the therapy, levetiracetam was added at the dosage of 250 mg b.i.d. or topiramate at 25mg o.i.d. Efficacy parameters included number of seizure-free days (SFDs), mean and percent reduction in seizure frequency (in general and by type), and number of seizure-free patients in the first 15 days of treatment compared to last 15 days of the baseline period. Sixty-one patients received levetiracetam and 61 topiramate. The general characteristics of the two treatment groups were similar. The total number of SFDs during 15 days before treatment was 637 with levetiracetam and 621 with topiramate; in the 15-day evaluation period the SFDs increased to 748 (17.4%) and 668 (7.6%), respectively (ANOVA, p<0.05). Twenty-six patients (42.6%) taking levetiracetam were seizure free compared to 10 (16.4%) receiving topiramate (chi-square, p=0.003). This open-label non-controlled study suggests an early efficacy of levetiracetam as add-on therapy in patients with refractory partial epilepsy: these results appear to confirm previous indications of a rapid onset of action and seem to suggest first evaluation of the patient at the dose of 500 mg/day before increasing to the considered minimum standard dose of 1000 mg/day, as some patients could respond to the starting dose.     

Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in patients with carbamazepine- or valproate-resistant epilepsy.

Lamotrigine is a broad-spectrum antiepileptic drug that blocks sodium channels, thereby inhibiting the pre-synaptic release of excitatory neurotransmitters. The primary aim of the study was to evaluate lamotrigine add-on therapy and consecutive monotherapy in patients with epilepsy whose seizures were not controlled by carbamazepine or valproate. One hundred and twenty six epilepsy patients at 18 centres in Poland were recruited into a lamotrigine substitution study. In all patients, existing seizures were poorly controlled with valproate (n= 63) or carbamazepine (n= 63) monotherapy. The study consisted of four phases: (1) a 4-week lamotrigine dose-escalation phase, (2) an 8-week lamotrigine add-on phase, (3) an 8-week carbamazepine/valproate withdrawal phase, and (4) an 8-week lamotrigine monotherapy phase. Of 126 patients recruited into the study, 107 (85%) completed dose-escalation and add-on therapy with lamotrigine and 85 (68%) completed lamotrigine monotherapy. Fifty percent of patients during add-on therapy and 53% during lamotrigine monotherapy experienced at least 50% reduction in total seizures (responders) compared to the pre-study period. Approximately 20% of patients during add-on therapy and 27% during lamotrigine monotherapy were seizure free. Total well-being was assessed using a Visual Analogue Scale with 62% of patients during add-on therapy and 60% in lamotrigine monotherapy reporting improvement in scores. Lamotrigine was generally well tolerated. Treatment was discontinued in 7% because of adverse events. In conclusion, lamotrigine is an effective AED in add-on therapy and monotherapy, it is safe and well tolerated, and successful conversion from add-on to monotherapy can be achieved in many cases. An additive effect between lamotrigine and valproate was observed.