自身对照左乙拉西坦添加治疗耐药性癫痫部分性发作的疗效及安全性

目的:评价左乙拉西坦作为添加剂治疗成人耐药性癫痫部分性发作的疗效和安全性。方法:本试验为单盲、前瞻性研究,27例耐药性癫痫病人在原用药基础上加用安慰剂16 wk,停用安慰剂,再加用左乙拉西坦治疗16 wk,X~2检验比较左乙拉西坦添加期疗效与安慰剂期疗效的差别,并观察其不良反应。结果:左乙拉西坦治疗有效而安慰剂无效的病例13例(48%),安慰剂治疗有效而左乙拉西坦无效的病例5例(19%),左乙拉西坦治疗有效的病例数明显高于安慰剂治疗有效的病例数(P＜0．05)。左乙拉西坦添加治疗期21例(78%)出现不良反应,安慰剂添加期20例(74%)出现不良反应。左乙拉西坦添加治疗期的不良反应主要有情绪异常、头晕、胃肠不适,部分病人有短暂性轻度血白细胞减少,没有病例因严重不良反应退出。结论:左乙拉西坦治疗成人耐药性癫痫部分性发作有效,且不良反应轻,对耐药性癫痫病人是一种有益的选择。     

左乙拉西坦单药治疗伴中央-颞区棘波的小儿良性癫痫近期疗效观察

左乙拉西坦(LEV)是吡拉西坦衍生物中的左旋乙基吡拉西坦,其化学名称为(s)-α-乙基-2-氧代-1-吡咯烷乙酰胺,分子式为C8H14N2O2.于1999年经美国FDA批准最初用于成人部分性癫痫发作,2005年6月又批准其口服片剂和溶液剂用于4岁或以上儿童部分性癫痫发作的辅助治疗.在北美60个试验中心对4～16岁难治性癫痫部分性发作的儿童进行多中心随机双盲和安慰剂对照的临床研究,结果:本品治疗组每周部分性发作频度明显减少,整个随机治疗阶段的有效应答率明显高于安慰剂组[1].2005年左乙拉西坦在国内新药申报获得通过.我们对40例伴中央-颞区棘波的小儿良性癫痫患儿使用左乙拉西坦单药治疗,观察其疗效及不良反应,报告如下.     

左乙拉西坦和苯妥英预防脑损伤后癫痫的Meta分析

目的比较左乙拉西坦和苯妥英单药预防脑损伤后癫痫的疗效和安全性。方法计算机检索Pubmed数据库、中国生物医学文献数据、CENTRAL数据库、Clinical Trials.gov和CNKI中比较左乙拉西坦和苯妥英预防脑损伤后癫痫的对照研究,研究者对文献质量进行严格评价和资料提取,选取脑损伤后癫痫发作情况和(或)不良反应情况(早期发作、晚期发作等)为结局指标,以风险比(RR)为效应量,利用STATA软件进行Meta分析。结果在检索出来的336篇文献中筛选出了10篇符合要求的文献。10项研究共纳入2 234例患者,Meta分析结果显示左乙拉西坦与苯妥英在预防早期发作疗效上无显著差异[RR=0.77,95%CI(0.37,1.61),P=0.08],按性别比例进行亚组分析,男性>50%的研究显示RR=0.88,95%CI(0.42,1.84),P=0.73;女性>50%的研究显示RR=0.32,95%CI(0.10,0.99),P=0.05,表明左乙拉西坦对女性患者可能有更好的疗效;对3篇报道晚期发作情况的研究进行Meta分析显示苯妥英对晚期发作的预防可能效果更好[RR=1.64,95%CI(1.11,2.42),P=0.01]。安全性的分析结果表明左乙拉西坦与苯妥英在不良反应方面无显著差异,但是苯妥英组更易出现严重不良反应。结论左乙拉西坦与苯妥英在脑损伤后癫痫预防的疗效上无显著差异,而左乙拉西坦在安全性方面具有一定优势。     

左乙拉西坦治疗脑卒中后癫痫的疗效观察

目的 观察左乙拉西坦治疗脑卒中后癫痫的临床疗效及安全性.方法 对50例脑卒中后癫痫患者在原用药基础上加用左乙拉西坦治疗24周,以基础期平均每月发作频率与添加治疗24周平均每月发作频率进行比较,观察左乙拉西坦添加治疗卒中后癫痫的临床疗效和不良反应.结果 左乙拉西坦治疗后总有效率78.0％ （39/50）,完全控制率为44.0％（22/50）;左乙拉西坦治疗期32.0％ （16/50）患者出现不良反应,主要有嗜睡乏力、纳差恶心、头晕、易激惹,无严重不良反应.结论左乙拉西坦治疗脑卒中后癫痫发作有效,不良反应少、耐受性好.     

左乙拉西坦和奥卡西平单药治疗新诊断儿童部分性癫痫的疗效及安全性分析

目的：观察左乙拉西坦（Levetiracetam,LEV）与奥卡西平（Oxcarbazepine,OXC）单药治疗新诊断部分性发作癫痫患儿的疗效和安全性。方法将68例新诊断部分性发作癫痫患儿随机分为两组,OXC组和LEV组各34例。观察两组的临床疗效、脑电图改变及不良反应。结果OXC组完成治疗32例,LEV组完成治疗34例。临床疗效比较OXC组总有效率为87．5％,LEV组总有效率为85．3％。两组总有效率比较差异无统计学意义（ P＞0．05）。脑电图改善情况比较OXC组有效率为50．0％,LEV组有效率为76．5％,LEV组有效率高于 OXC组,差异有统计学意义（P＜0．05）。 LEV组不良反应发生率低于OXC组,差异有统计学意义（P＜0．05）。结论奥卡西平与左乙拉西坦治疗儿童部分性发作癫痫临床疗效相当,但左乙拉西坦对脑电图改善优于奥卡西平,且不良反应少,安全性更高。     

美FDA批准左乙拉西坦用作附加药物治疗1月龄～4岁婴儿至儿童部分癫痫发作患者

2012年1月,美国FDA批准扩展UCB公司的左乙拉西坦片剂和口服液(levetiracetam/Keppra)的适用对象,即也允许该药用作附加药物治疗1月龄～4岁婴儿至儿童癫痫患者的部分癫痫发作。左乙拉西坦先前已在美国获准用作附加药物治疗≥4岁儿童至成人癫痫患者的部分癫痫发作。左乙拉西坦先前亦已在美获准治疗其它广泛癫痫发作类型的癫痫患者。     

左乙拉西坦治疗小儿癫痫的疗效和安全性评价

目的:根据小儿癫痫患者的病情特征,采用左乙拉西坦进行治疗,分析其疗效与安全性。方法:将某院治疗的小儿癫痫患者中随机抽取32例,按照其住院号的先后顺序将其分为研究组和参照组。研究组患者服用左乙拉西坦进行治疗,参照组采用卡马西平缓释胶囊进行治疗,治疗结束后将两组患者的癫痫发作频率、临床总有效率、不良反应情况等进行分析比较。结果:与参照组比较,研究组患者的癫痫发作频率、癫痫发作持续时间明显较短,临床总有效率(93.8%)明显较高,且不良反应率(18.8%)较低,差异具有统计学意义。结论:左乙拉西坦治疗小儿癫痫的治疗效果较好,且安全性高、无明显不良反应,在今后的临床实践中值得应用。     

卡马西平联合左乙拉西坦或托吡酯治疗儿童难治性部分性发作癫痫的疗效比较

目的:探究卡马西平联合左乙拉西坦或托吡酯治疗儿童难治性部分性发作癫痫的临床疗效。方法:选取2015年7月—2016年7月进行治疗的儿童难治性部分癫痫患者80例,随机分为A组和B组,每组40例。A组采用卡马西平联合左乙拉西坦治疗,B组采用卡马西平联合托吡酯治疗。对两组临床治疗有效率、平均癫痫发作次数及不良反应发生情况进行对比。结果:A组治疗总有效率(95%)高于B组(75%)(P<0.05)。A组治疗1个月、2个月后癫痫发作次数与B组相比差异无统计学意义(P>0.05);治疗4个月后,A组发作次数明显少于B组(P<0.05)。A组不良反应发生率与B组相比差异无统计学意义(P>0.05)。结论:卡马西平联合左乙拉西坦或托吡酯治疗儿童难治性部分性发作癫痫临床疗效显著,但与托吡酯相比,卡马西平联合左乙拉西坦治疗可在提高治疗效果的同时,使癫痫发作次数明显减少,且不良反应发生率较低。     

左乙拉西坦添加治疗成人癫痫部分性发作的临床效果

目的分析左乙拉西坦添加治疗成人癫痫部分性发作的临床效果。方法成人癫痫部分性发作患者94例,所有患者均行左乙拉西坦治疗,对其临床效果进行观察分析。结果94例患者治疗总有效率为68．09％;治疗过程30例患者发生轻度不良反应（31．91％）,25例患者未采取措施症状自行消失,5例采取减量措施后症状消失;添加治疗后患者的脑电图（EEG）异常情况较治疗前明显改善（P〈0．05）。结论左乙拉西坦添加治疗成人癫痫部分眭发作效果较好,值得临床推广应用。     

新药研究与开发

FDA批准左乙拉西坦的新适应证美国FDA批准UCB公司的左乙拉西坦（levetiracetam）用于成年和6岁以上儿童特发性全身性癫痫全面性强直阵挛发作的辅助治疗。这次新适应证申报是根据164名顽固性癫痫病人的临床试验结果，72％病人加用该药后，每周全身强直一阵挛癫痫发作减少50％，安慰剂组为45％。其中24％病人在20周用药期间完全没有出现癫痫，而安慰剂组为8％（P〉0．009）。     

加巴喷丁胶囊添加治疗癫痫的临床疗效和安全性

目的 :评价国产加巴喷丁的临床疗效和安全性。方法 :采用多中心、双盲、安慰剂对照、平行试验方法观察加巴喷丁添加治疗癫痫部分性发作(PS)和泛化性全身强直 阵挛发作 (SGTCS) 2 4wk。分 2组 :加巴喷丁组 (原基础抗癫痫药 +加巴喷丁胶囊 90 0mg·d- 1) 110例 ,对照组 (原基础抗癫痫药 +安慰剂 ) 10 8例。结果 :加巴喷丁组总有效率5 2 .7% (5 8/ 110 ) ,对照组 31.5 % (34/ 10 8) ,2组比较 ,P <0 .0 1;2组基线期发作次数≥ 4次 (2 8d)病人的疗效比较 ,P <0 .0 5 ;不同发作类型的疗效比较SGTCS >复杂部分性发作 (CPS) >简单部分性发作(SPS) (P <0 .0 1) ;2组痫样放电减少≥ 2 5 %的疗效比较 ,P <0 .0 5。2组不良反应发生率比较差异无显著性 (P >0 .0 5 )。结论 :国产加巴喷丁添加治疗对控制癫痫PS和SGTCS是有效而安全的。     

Potential of levetiracetam in mood disorders: a preliminary review

Levetiracetam is a newer antiepileptic agent that was first approved by the US FDA in 1999 as an adjunctive therapy for the treatment of refractory partial epilepsy in adults. Since then, it has been approved for a wider patient population, i.e. as adjunctive therapy for partial seizures in patients >4 years of age (worldwide) and as first-line monotherapy for partial seizures in patients >16 years of age (in Europe); and as adjunctive therapy for juvenile myoclonic seizures (in Europe and the US). It has a favourable pharmacokinetic profile and appears to act at a specific site in the CNS. Pharmacodynamic evidence indicates that levetiracetam indirectly facilitates GABAergic function, and an increasing body of evidence suggests an important role for GABA in the pathophysiology of mood disorders. Preclinical studies using animal models of depression, anxiety and mania provide evidence for levetiracetam as a mood stabiliser. Preliminary clinical evidence from case reports and open-label pilot studies indicates that the drug, both as add-on therapy and as monotherapy, has efficacy in a wide range of bipolar spectrum disorders. Most recently, a 31% remission rate was reported in patients with bipolar disorder who were in the depressed phase at baseline and who received levetiracetam as add-on therapy for 8 weeks in an open-label trial. While these results are encouraging, placebo-controlled data are needed to further clarify the role of levetiracetam in the treatment of mood disorders.     

An assessment of levetiracetam as an anti-epileptic drug

A brief review of epilepsy as a disease, anti-epileptic drugs (AEDs) and methods of evaluation of AEDs are presented as a background for the assessment of levetiracetam which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. The exact mechanism of action of levetiracetam is not known but its action differs from that of other anti-epileptic drugs. A specific binding site for levetiracetam has been identified and is possibly related to anticonvulsant activity. Levetiracetam offers an effective and broad spectrum treatment of epileptic seizures, partial as well as generalised epilepsy. Levetiracetam has been shown to be effective in genetic and kindled animal models of epilepsy and against chemoconvulsant-induced partial epileptic seizures. Levetiracetam has a near perfect pharmacokinetic profile, with rapid absorption following oral administration, excellent bioavailability, quick attainment of steady-state concentrations, linear kinetics and minimal plasma protein binding. Levetiracetam does not interact with commonly used drugs and other AEDs. In recent Phase III clinical trials, the responder rate was 39.4 - 42.1% on 3000 mg dose, compared with placebo rates of 10.9 - 16.7%. Levetiracetam has a favourable safety profile and the most frequently reported adverse events were somnolence, asthenia and dizziness. Overall, levetiracetam is considered to have several advantages over current AEDs.     

An assessment of levetiracetam as an anti-epileptic drug

A brief review of epilepsy as a disease, anti-epileptic drugs (AEDs) and methods of evaluation of AEDs are presented as a background for the assessment of levetiracetam which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. The exact mechanism of action of levetiracetam is not known but its action differs from that of other anti-epileptic drugs. A specific binding site for levetiracetam has been identified and is possibly related to anticonvulsant activity. Levetiracetam offers an effective and broad spectrum treatment of epileptic seizures, partial as well as generalised epilepsy. Levetiracetam has been shown to be effective in genetic and kindled animal models of epilepsy and against chemoconvulsant-induced partial epileptic seizures. Levetiracetam has a near perfect pharmacokinetic profile, with rapid absorption following oral administration, excellent bioavailability, quick attainment of steady-state concentrations, linear kinetics and minimal plasma protein binding. Levetiracetam does not interact with commonly used drugs and other AEDs. In recent Phase III clinical trials, the responder rate was 39.4 - 42.1% on 3000 mg dose, compared with placebo rates of 10.9 - 16.7%. Levetiracetam has a favourable safety profile and the most frequently reported adverse events were somnolence, asthenia and dizziness. Overall, levetiracetam is considered to have several advantages over current AEDs.     

Prospective research on the efficacy and safety of oxcarbazepine as monotherapy and add-on therapy for partial epilepsy

The purpose of our research was to evaluate the efficacy, tolerance, and safety of oxcarbazepine (OXC) as monotherapy and add-on therapy for partial epilepsy. We carried out a prospective clinical follow-up trial at the Epilepsy Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Sixty-seven patients with partial epilepsy received OXC therapy. The patients were randomly divided into a monotherapy group and an add-on therapy group. We observed the efficacy and safety in the first three months and the following three months respectively, and compared them with each other. There was a significant difference in the decrease of seizure frequency between the two groups (P = 0.002). There was a significant difference in the percentage of seizure-free between the monotherapy and the add-on therapy groups in the first three months (P = 0.02), and there were also statistical differences in the 50% response rate (P = 0.017) and the percentage of seizure-free in the following three months (P = 0.019). No difference was found in the 50% response rate, the 75% response rate, and the percentage of seizure-free between the first three months and the following three months in the whole group and the two subgroups (P>0.05). The incidence rate of side effects due to the therapy was 19.40% (13 of 67). The side effects were mainly found in the first three months. It is concluded that OXC is the first-line anti-epileptic drug (AED) for partial seizures, and could be used as the monotherapy and add-on therapy for newly diagnosed patients and patients that failed to tolerate or benefit from other AEDs.     

Levetiracetam: a review of its use in epilepsy

Levetiracetam (Keppra?, E Keppra?) is an established second-generation antiepileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy. Levetiracetam has a novel structure and unique mechanisms of action. Unlike other AEDs, the mechanisms of action of levetiracetam appear to involve neuronal binding to synaptic vesicle protein 2A, inhibiting calcium release from intraneuronal stores, opposing the activity of negative modulators of GABA- and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, levetiracetam inhibits N-type calcium channels. Levetiracetam is associated with rapid and complete absorption, high oral bioavailability, minimal metabolism that consists of hydrolysis of the acetamide group, and primarily renal elimination. It lacks cytochrome P450 isoenzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs, including other AEDs. The efficacy of oral immediate-release levetiracetam in controlling seizures has been established in numerous randomized, double-blind, controlled, multicentre trials in patients with epilepsy. Adjunctive levetiracetam reduced the frequency of seizures in paediatric and adult patients with refractory partial onset seizures to a significantly greater extent than placebo. Monotherapy with levetiracetam was noninferior to that with carbamazepine controlled release in controlling seizures in patients with newly diagnosed partial onset seizures. Levetiracetam also provided seizure control relative to placebo as adjunctive therapy in patients with idiopathic generalized epilepsy with myoclonic seizures or GTC seizures. In addition, patients receiving oral levetiracetam showed improvements in measures of health-related quality of life relative to those receiving placebo. Although treatment-emergent adverse events were commonly reported in the clinical trials of levetiracetam, the overall proportion of patients who experienced at least one treatment-emergent adverse event was broadly similar in the levetiracetam and placebo treatment groups, with most events being mild to moderate in severity. Levetiracetam is not associated with cognitive impairment or drug-induced weight gain, but has been associated with behavioural adverse effects in some patients.     

左乙拉西坦单药治疗≤4岁儿童癫痫112例临床观察

目的：评价左乙拉西坦（LEV）治疗≤4岁儿童癫痫的疗效及安全性。方法：对该院2010年1月至2012年1月LEV单药治疗的112例癫痫患儿（≤4岁）进行疗效及不良反应等观察，起始剂量10 mg·kg^-1·d^-1，每1周增加10 mg·kg^-1·d^-1，逐渐加量至最小有效剂量维持。结果：14例提前退出，98例随访时间≥1年，1年保留率为87.5%；78.6%（77/98）的患儿发作减少≥50%，48%（47/98）的患儿无发作；部分性发作的无发作率为50.9%（28/55），有效率为30.9%（17/55），全面性发作的无发作率45.0%（18/40），有效率为30.0%（12/40），部分性和全面性发作疗效比较差异无统计学意义（p>0.05）；不良反应主要包括嗜睡7.1%（7/98）、行为异常5.1%（5/98）、乏力4.1%（4/98）、食欲不振2.0%（2/98）、皮疹1.0%（1/98）等，不良反应通常发生在治疗的1个月内，症状轻微，绝大部分对症处理后逐渐消失。结论：LEV单药治疗≤4岁儿童癫痫的疗效肯定，安全性好。     

左乙拉西坦治疗新生儿难治性惊厥的临床疗效及影响预后的相关因素

目的:探讨左乙拉西坦治疗新生儿难治性惊厥的临床疗效及影响预后的相关因素.方法:选取2016年4月至2018年3月海南省妇女儿童医学中心收治的惊厥新生儿80例,分析左乙拉西坦治疗新生儿难治性惊厥的临床疗效,将治疗有效患儿纳入预后良好组(n=62),治疗无效患儿纳入预后不良组(n=18),通过Logistic多元回归分析新...     

Levetiracetam. A review of its adjunctive use in the management of partial onset seizures

Levetiracetam, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is approved for use as adjunctive therapy in adult patients with partial onset seizures. Oral levetiracetam 1000, 2000 and 3000 mg/day administered as adjunctive therapy for up to 18 weeks significantly increased responder rates and reduced seizure frequency compared with placebo in 3 well designed pivotal trials in adults with treatment-refractory partial seizures with or without secondary generalisation. Levetiracetam 3000 mg/day also significantly increased the number of seizure-free patients, but the effects of levetiracetam 1000 and 2000 mg/day on this end-point were unclear. Effects on seizure severity were not assessed in these trials. Although not yet approved as monotherapy or for use in paediatric patients, efficacy was observed with levetiracetam 3000 mg/day as monotherapy in adult patients with refractory partial seizures with or without secondary generalisation and with the 10 to 40 mg/kg/day dosage as adjunctive therapy in children with refractory partial seizures. However, these data are limited. Oral levetiracetam 1000, 2000 and 3000 mg/day as adjunctive therapy is generally well tolerated with an overall incidence of adverse events similar to that observed with placebo. The most commonly reported events in individual clinical trials were CNS-related and included somnolence, asthenia, headache and dizziness. Levetiracetam administered as adjunctive therapy does not appear to interact with other anticonvulsant drugs, and no clinically relevant interactions were observed between levetiracetam and digoxin, warfarin or probenecid; oral contraceptive protective efficacy was also not affected by levetiracetam. CONCLUSIONS: Levetiracetam is a new anticonvulsant agent with a favourable tolerability profile and a low potential for drug interactions. It has shown efficacy as adjunctive therapy in patients with treatment-refractory partial onset seizures with or without secondary generalisation in clinical trials. Direct comparative trials with other anticonvulsant agents are not yet available, but placebo-controlled clinical evidence to date suggests that levetiracetam (1000, 2000 and 3000 mg/day) is a useful option as adjunctive therapy in patients with this subtype of epilepsy.     

Brivaracetam for the treatment of epilepsy

Introduction: Approximately one third of patients with epilepsy fail to respond to existing medications. Levetiracetam is an effective antiepileptic drug (AED) postulated to act by binding to synaptic vesicle protein 2A. Brivaracetam is a novel high affinity SV2A ligand with approximately 20-fold higher affinity for SV2A protein than levetiracetam. It is at an advanced stage of clinical development for treatment of epilepsy.

Areas covered: This article reviews animal data, pharmacokinetics, and phase 1-3 data of Brivaracetam treatment of epilepsy. Brivaracetam has broad-spectrum anticonvulsant activity in animal models.

Expert Opinion: Phase 1 studies indicated that single oral doses of 5-800 mg and repeated oral doses of up to 600 mg were well tolerated and showed favorable pharmacokinetic profile. Phase 2 studies indicated good safety and tolerability of brivaracetam in the dose range of 5-150 mg/day and provided proof of concept for efficacy in treating refractory partial onset seizures. Efficacy and safety have been evaluated in 4 phase 3 studies with dose range of 5-200 mg which have demonstrated efficacy in the range of 100-200 mg/day dose and, in most studies, also with 50 mg/day dose, and good safety and tolerability profile across 5-200 mg doses in adjunctive treatment of refractory partial onset seizures.