儿童失神性癫痫：乙琥胺优于丙戊酸和拉莫三嗪

儿童失神性癫痫为儿童期癫痫最常见的类型,通常使用乙琥胺、丙戊酸或拉莫三嗪治疗。但这三种常用药,哪种效果最佳且儿童最易耐受仍然未知,本研究对此进行了考察。     

拉莫三嗪添加治疗儿童癫痫的疗效与安全性Meta分析

目的评价拉莫三嗪添加治疗儿童癫痫的疗效和安全性。方法检索PubMed、EMbase、Cochrane图书馆、维普、万方、中国生物医学文献数据库和中国期刊全文数据库,检索时限为从建库起至2014年10月,收集拉莫三嗪添加治疗儿童癫痫的临床试验。由两位研究者按照纳入与排除标准,进行文献筛选、资料提取和纳入研究的方法学质量评价。采用RevMan 5.2软件进行Meta分析。结果共纳入5项研究,375例患儿。Meta分析结果显示:拉莫三嗪添加治疗儿童癫痫有效率高于丙戊酸单药治疗,与拉莫三嗪单药有效率相当。添加治疗不增加不良反应发生率。结论拉莫三嗪添加治疗儿童癫痫疗效确切,耐受性较好。对抗癫痫疗效不佳或使用丙戊酸受限的患儿,拉莫三嗪添加治疗是一种较好的选择。     

乙琥胺与拉莫三嗪治疗儿童失神性癫痫的疗效比较

目的观察乙琥胺与拉莫三嗪治疗儿童失神性癫痫的疗效。方法 2010年至2012年2年间诊治的失神性癫痫患儿120例,随机分为2组,观察乙琥胺和拉莫三嗪单用对儿童失神性癫痫的疗效、耐受性以及不良反应。结果治疗16周之后,乙琥胺无治疗失败,总有效率为63.33%,拉莫三嗪为31.66%,并且乙琥胺的不良反应发生率低,为10.00%,且较轻微,拉莫三嗪的不良反应发生率高于乙琥胺,为28.74%,以皮疹多见。结论对于失神性癫痫患儿,乙琥胺的疗效优于拉莫三嗪且不良反应发生率低。     

拉莫三嗪治疗癫痫患者的经济学效率研究的系统评价

目的:了解拉莫三嗪治疗不同发作类型的癫痫患者的经济学效率。方法:对最近10年MEDLINE、EMBASE和中国期刊全文期刊数据库中公开发表的药物经济学研究的原著文献进行系统评价。结果:共检索到6篇可用文献,其中成本-效用分析和成本-效果分析文献各3篇。成本-效用分析结果显示,以卡马西平为比较组,拉莫三嗪单药治疗部分发作患者,每增加一个质量调整生命年(QALY)需要的费用最少,为23344美元,加巴喷丁最高,为187857美元;以丙戊酸为比较组,拉莫三嗪单药治疗全身性发作和不能分类的发作患者,每增加一个QALY需要的费用高于托吡酯。结论:拉莫三嗪单药治疗部分发作性癫痫的增量成本-效用比优于托吡酯和加巴喷丁;而单药治疗全身性发作和不能分类发作患者劣于托吡酯。     

拉莫三嗪单药添加-替换治疗失神癫痫18例临床观察

目的观察拉莫三嗪(LTG)单药治疗失神癫痫(包括儿童失神癫痫和少年失神癫痫)的疗效及安全性。方法对18例失神癫痫患儿采用添加-替换LTG治疗开放性自身对照临床试验。结果18例患儿中,15例发作频度减少≥50%(83.3%),12例发作完全消失,显示单药LTG治疗失神癫痫疗效较佳;副作用小,仅5例有头痛、头晕、嗜睡等副作用,可自然消失或在减量后消失,未发现皮疹等过敏反应。结论LTG是一有效抗癫痫药,特别适用于小儿失神癫痫。     

拉莫三嗪添加-替换治疗对丙戊酸无效的癫痫患者的疗效观察

目的探讨拉莫三嗪添加-替换治疗对丙戊酸无效的癫痫患者的临床疗效。方法选取2010年1月-2014年1月期间收治的丙戊酸治疗无效的28例癫痫患者为研究对象,根据其临床资料进行回顾性分析,观察拉莫三嗪添加-替换治疗曾用丙戊酸治疗无效的癫痫患者的临床疗效。结果 25例患者完成联合用药阶段,其中完全控制为15例,有效为8例,总有效率为92.0%;17例患者转换为拉莫三嗪单药治疗,其中完全控制为9例,有效为2例,总有效率为64.7%,拉莫三嗪单药与联合用药阶段的完全控制率、总有效率比较,差异具有统计学意义（P〈0.05）。结论拉莫三嗪联合丙戊酸治疗对丙戊酸无效的癫痫患者优于单用拉莫三嗪的治疗效果,患者产生的不良反应比较少,值得在临床实践中广泛的应用和推广。     

拉莫三嗪单药治疗癫痫的临床疗效和安全性

目的:探讨在治疗癫痫的过程中应用拉莫三嗪单药的临床疗效和安全性.方法:随机选取我院2015年2月～2016年2月收治的80例确诊为癫痫的患者作为研究对象,平均分为两组.对对照组给予丙戊酸钠进行治疗,对观察组给予拉莫三嗪单药进行治疗.治疗期间将临床疗效及不良反应发生率进行比较分析.结果:给予拉莫三嗪单药的观察组,临床疗效高达95％明显高于试验组的80％,不良反应发生率更低.结论:拉莫三嗪单药应用于癫痫治疗,能有效改善癫痫发作,对比传统的抗癫痫药物丙戊酸钠临床效果更好,且不良反应更少,从而减轻患者、家属的负担,值得推广.     

拉莫三嗪治疗儿童和成人癫痫的耐受性和安全性评价

拉莫三嗪是临床广泛应用的抗癫痫药物之一。欧洲专家共识2007、中国癫痫诊疗指南、美国神经病学学会和美国癫痫学会均推荐为治疗顽固性部分性癫痫发作、成人或儿童原发性全身性癫痫、儿童和青少年失神发作、青少年肌阵挛性癫痫等的首选药物。本文对拉莫三嗪治疗各种类型癫痫的耐受性和安全性进行总结,从认知、内分泌、性功能、体重和社会心理等方面评价拉莫三嗪治疗的安全性。     

左乙拉西坦与丙戊酸钠用于颞叶癫痫添加治疗的疗效对比

目的：对比左乙拉西坦和丙戊酸钠对6个月单药治疗无效的颞叶癫痫（temporal lobe epilepsy,TLE）患者进行添加治疗的疗效。方法：对使用卡马西平、奥卡西平、拉莫三嗪单药治疗6个月无效的180例TLE患者分别添加丙戊酸钠、左乙拉西坦进行联合治疗,对比两者疗效。结果：卡马西平、奥卡西平、拉莫三嗪单药治疗6个月无效的TLE患者添加左乙拉西坦或丙戊酸钠联合治疗后发作频率有明显降低,其中左乙拉西坦较丙戊酸钠疗效更好,结果有显著性差异（P<0.05）。结论：对使用卡马西平、奥卡西平、拉莫三嗪单药治疗6个月无效的TLE患者,添加左乙拉西坦疗效优于丙戊酸钠。     

丙戊酸钠治疗儿童失神癫痫的疗效

目的:观察丙戊酸钠单剂治疗儿童失神癫痫的疗效。方法:选择1990年4月～2007年5月在我院诊断失神癫痫,患儿123例首选口服丙戊酸钠治疗,发作未能完全控制者加用氯硝西泮,观察其疗效并进行追踪。结果:123例患儿中,丙戊酸钠单药治疗后发作完全控制105例,控制率84.4%,未能完全控制的18例,加用氯硝西泮后,患儿发作完全控制。追踪34例停药后的患儿9个月～10年,其中2例复发,占5.9%。结论:丙戊酸钠单药治疗失神癫痫能使84.4%的患儿发作完全控制,发作不能完全控制者应加用氯硝西泮,二者联合用药可使患儿的临床发作得到完全控制,且起效快。     

Treatment of idiopathic generalized epilepsy – a review of the evidence

Introduction: Epilepsy is stratified into idiopathic partial, symptomatic partial, idiopathic generalized (IGE) and symptomatic generalized epilepsies.

Areas covered: The epidemiology and clinical characteristics of IGE are reviewed in this paper. Clinically, IGE is characterized by the occurrence of any of the following three seizure types: absence seizures, myoclonic seizures and primarily generalized tonic-clonic seizures. To assess the presence of evidence-based data on the treatment of IGE, the literature was extensively reviewed for studies evaluating the treatment of IGE with various antiepileptic drugs. These studies were stratified into four classes based on recently described criteria. Class I studies were considered as providing evidence of the efficacy of the drug in patients with IGE. Finally, suggestions to evaluate the efficacy of a study drug in patients with IGE are presented.

Expert opinion: Based on the reviewed data, there is strong evidence-based data to support the use of valproate and ethosuximide for the treatment of childhood absence seizures; for the use of topiramate as monotherapy or adjunctive therapy for patients with primarily generalized tonic-clonic seizures; for the use of adjunctive therapy with lamotrigine for the treatment of primarily generalized tonic-clonic seizures; and for the use of levetiracetam as adjunctive therapy for the treatment of myoclonic or primarily generalized tonic-clonic seizures. To evaluate a new drug as a potential treatment for patients with IGE requires a rational methodology, discussed in this review.     

Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary

BackgroundWAG/Rij rats represent a validated genetic animal model of epileptogenesis, absence epilepsy and depressive-like comorbidity. Some treatments (e.g. ethosuximide), using specific protocols, prevent the development of spontaneous absence seizures. Accordingly, ethosuximide increases remission occurrence in children with childhood absence epilepsy in comparison to valproic acid. Considering that in this animal model, antiepileptogenic effects are, in some cases, not retained over time, we studied whether the antiepileptogenic effects of both ethosuximide and levetiracetam (which also possesses antiepileptogenic effects in this and other animal epilepsy models) would be retained 5 months after drug suspension.MethodsWAG/Rij rats of ?1 month of age were treated long-term with one of the two drugs at a dose of ?80 mg/kg/day for 17 consecutive weeks; 1 and 5 months after drug suspension, the development of absence seizures as well as depressive-like behaviour were assessed by EEG recordings and the forced swimming test (FST).ResultsIn agreement with a previous report, both drugs continued to show antiepileptogenic effects 1 month after their discontinuation. Furthermore, ethosuximide improved depressive-like behaviour, whereas in contrast, levetiracetam worsened this symptom. However, none of the drugs maintained their antiepileptogenic effects 5 months after suspension, and in addition, animal behaviour in the FST returned to control conditions.ConclusionOverall, these results demonstrate that the antiepileptogenic effects of both ethosuximide and levetiracetam on absence seizure development and associated depressive-like behaviour in this model are only temporary.     

The tolerability of lamotrigine in children.

Lamotrigine is a novel anticonvulsant, which has proven to be effective both as add-on and monotherapy. 13 studies have demonstrated efficacy in 1096 children with a variety of seizure types. Tolerability information in these studies was collected in a standard fashion, where investigators reported all adverse events regardless of the perceived relationship to the test therapies. Generally, lamotrigine treatment in these clinical trials was generally given at higher initial doses and faster dose escalations than are currently recommended. Most adverse events associated with lamotrigine were mild to moderate in severity and did not result in discontinuation of treatment. Results from placebo-controlled, add-on trials showed that 85% of lamotrigine recipients experienced an adverse event compared with 83% of placebo recipients. Lamotrigine was associated with an increased risk of adverse events in the nervous system (dizziness, tremor, ataxia, and diplopia), gastrointestinal tract (nausea), and urinary tract (infection). The incidence of most adverse events was lower among lamotrigine recipients in monotherapy trials than in add-on trials, suggesting that concurrent anticonvulsant treatment or drug interactions can be confounding risk factors above that of lamotrigine treatment alone. Skin rash associated with hospitalisation and the discontinuation of study drug was reported more frequently by lamotrigine recipients than by placebo recipients and more frequently by children than by adults. The simultaneous use of valproic acid (sodium valproate) was associated with an increased incidence of rash. Lamotrigine, an effective broad spectrum anticonvulsant, is well tolerated in children. The qualitative features of adverse events that occur with lamotrigine treatment are similar for children and adults. The incidence of rash may be reduced with proper initial dosing and dose escalation.     

Anticonvulsant drugs for generalized tonic-clonic epilepsy

Introduction: Primary generalized tonic clonic seizures (pGTCS) are still linked to major concerns for the clinic and hazards for patients suffering from idiopathic generalized epilepsy (IGE), so a quick search of the most effective and appropriate therapy is needed to control them. The key criteria for proper treatment are syndromic diagnosis and distinction between newly diagnosed and refractory patients. Other criteria include age, gender and comorbidities.

Areas covered: Treatment for pGTCS has expanded in the last two years, with new antiepileptic drugs like perampanel joining valproic acid, lamotrigine, levetiracetam, topiramate, while further evidence-based data are required for zonisamide and lacosamide.

Expert opinion: Currently, valproic acid can be considered as a first choice in male or menopausal women, and in the absence of weight issue, both in adults and in children, and in the absence of side effects such as insomnia and headache. Today, valproic acid is not recommended in child-bearing age and in relation to possible cognitive problems, especially in children. Lamotrigine and levetiracetam can be a viable alternative as a first choice. Topiramate is also effective as a first choice, but concerns may arise from its potential cognitive and memory adverse side effects. Additionally, perampanel and lacosamide are promising treatments.     

Lamotrigine. A review of its use in childhood epilepsy

Lamotrigine is an antiepileptic agent that blocks use-dependent voltage-sensitive sodium channels, thereby preventing excitatory neurotransmitter release. However, this mechanism does not explain the broad range of clinical efficacy of this agent. In noncomparative trials, adjunctive lamotrigine (< or = 15 mg/kg/day) improved seizure control in children and adolescents with various refractory seizure types, with about 29 to 90% of patients showing a > or = 50% reduction in seizure frequency after > or = 3 months' treatment. Lamotrigine was particularly effective in generalised seizures, especially absence seizures and those related to the Lennox-Gastaut syndrome. In one placebo-controlled study, 33% of children and young adults (aged 3 to 25 years) with refractory Lennox-Gastaut syndrome had a reduction in seizure frequency of > or = 50% after 16 weeks of adjunctive lamotrigine treatment, compared with 16% of placebo recipients (p = 0.01). Significant reductions in seizure frequency when compared with placebo were also observed in patients with refractory generalised and partial seizures. The use of lamotrigine has also been associated with beneficial effects on cognition and behaviour. Adverse events associated with lamotrigine are primarily neurological, gastrointestinal and dermatological and are typically mild or moderate and transient with the exception of a potentially serious rash. Maculopapular or erythematous skin rash occurred in approximately 12% of paediatric patients (aged < 16 years) treated with lamotrigine and was the most common reason for treatment discontinuation. More severe forms of rash, including Stevens-Johnson syndrome, occasionally occurred, with a 3-fold higher incidence in children (approximately 1%) than adults (approximately 0.3%). However, lamotrigine treatment in paediatric trials was generally given at higher initial doses and faster dose escalations than recently revised recommendations. These factors, as well as concomitant use of valproic acid (valproate sodium), are associated with an increased risk of rash. CONCLUSION: Although published clinical evidence is still limited in paediatric populations, lamotrigine is an effective and generally well tolerated broad-spectrum agent for adjunctive treatment of refractory seizures in children, most notably in those with Lennox-Gastaut syndrome. Results of direct comparisons with other antiepileptic agents are needed to determine more clearly the place of lamotrigine, particularly relative to newer agents, in the treatment of childhood epilepsy. The potential for serious rash in recipients of lamotrigine should also be kept in mind. Nonetheless, lamotrigine is a welcome addition to the available treatments for refractory childhood epilepsy, particularly Lennox-Gastaut syndrome.     

Conversion to lamotrigine monotherapy from valproate monotherapy in older adolescent patients with epilepsy

ABSTRACT

Background: Pharmacokinetic interactions can make necessary anti-epileptic medication (AED) changes hazardous for children with epilepsy. We report the utility of a dosing algorithm designed to maintain stable trough lamotrigine (LTG) concentrations during conversion from valproate (VPA) to LTG monotherapy in adolescents aged 16–20 years.

Methods: Patients were enrolled into the study if they required a change in their AED regimen due to lack of efficacy or intolerable side effects. Conversion to LTG monotherapy took place in a four part treatment algorithm. Lamotrigine was escalated according to a target dose of 200?mg/day over 8‐weeks. Valproate was withdrawn over a period of 2–6 weeks, depending on the initial dose. Lamotrigine dose was further escalated to 500?mg/day and continued for four weeks as monotherapy. Trough serum concentrations of LTG were measured during each phase of the trial.

Results: Twelve of 16 patients completed the study. After the LTG escalation to 200?mg/day, mean trough serum concentrations of 8.0?μg/mL did not differ significantly from the 9.5?μg/mL after VPA withdrawal or the 9.2?μg/mL after 4 weeks of monotherapy at 500?mg/day. Adverse events led to premature discontinuation for one subject. Two subjects withdrew due to worsening seizures during LTG monotherapy possibly due to non-compliance. Limitations of the trial include the open label design and small sample size of the sub-analysis.

Conclusion: In adolescent patients, this algorithm produces stable LTG serum concentrations with favorable tolerability during a transition from VPA to LTG monotherapy.     

拉莫三嗪单药治疗新诊断小儿局限性癫痫41例疗效观察

目的：探讨拉莫三嗪单药对局限性发作癫痫患儿治疗效果及不良反应。方法首次确诊为部分性发作癫痫患儿41例加用拉莫三嗪治疗12个月,治疗前后分别观察治疗效果及不良反应。结果拉莫三嗪单药治疗41例患儿12个月,总有效率为92.68%,其中完全控制率为80.49%,有效控制率为12.20%,无效控制率为4.88%,不良反应率为9.51%。结论拉莫三嗪是治疗局限性发作癫痫患儿疗效确切、安全性好、可单药使用的药物。     

拉莫三嗪联合丙戊酸钠治疗脑卒中继发性癫痫的疗效分析

目的 探讨拉莫三嗪联合丙戊酸钠治疗脑卒中继发性癫痫的效果。方法 脑卒中继发性癫痫患者98例按照随机数字表法分为治疗组与对照组各49例,两组都给予脑卒中常规治疗,对照组予口服丙戊酸钠,治疗组在此基础上予拉莫三嗪。记录发作情况、发作次数及每次持续时间,监测药物不良反应。治疗期间每月随访1次,复查血、尿常规,血电解质,血脂,肝肾功能等。结果 治疗后治疗组的总有效率为95.8%,对照组为76.6%,治疗组的总有效率明显高于对照组(P<0.05)。治疗后两组的癫痫发作次数以及持续时间有明显下降,与治疗前对比差异明显(P<0.05);同时治疗后治疗组的癫痫发作次数以及持续时间也明显少于对照组(P<0.05)。治疗后1年,两组脑电图有痫样放电及累及导联数减少,组内及组间差异均有统计学意义(P<0.05)。治疗期间治疗组的皮疹、感觉异常、胃肠道反应等不良反应的总发生率与对照组比较,差异无统计学意义(P>0.05)。结论 拉莫三嗪联合丙戊酸钠治疗脑卒中继发性癫痫能提高治疗效果,促进癫痫症状的消失,不良反应少,值得推广应用。     

Review of lamotrigine and its clinical applications in epilepsy

Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.