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。     

观察卡马西平和托吡酯与丙戊酸钠治疗脑炎继发癫痫的临床效果

目的 观察卡马西平、托吡酯、丙戊酸钠治疗脑炎继发癫痫的临床效果.方法 选取2010年1月-2012年1月灌云县人民医院接受治疗的108例脑炎继发癫痫患者作为研究对象,将其随机分为卡马西平组、托吡酯组和丙戊酸钠组,各36例.观察3组患者的临床疗效.结果 治疗后卡马西平组、丙戊酸钠组和托吡酯组总有效率分别为75.63%（25/36）、77.78%（28/36）和79.63%（29/36）,3组间比较差异无统计学意义（P＞0.05）.结论 卡马西平、托吡酯、丙戊酸钠治疗脑炎继发癫痫的疗效相当;对脑炎继发癫痫患者采取单药治疗时,卡马西平对部分性发作有较好疗效,托吡酯与丙戊酸钠适宜治疗各种类型脑炎继发癫痫患者,同时托吡酯具有较少不良反应.     

托吡酯、卡马西平与丙戊酸钠治疗脑炎继发癫痫的效果观察

目的分析托吡酯、卡马西平与丙戊酸钠治疗脑炎继发癫痫效果。方法选取我院在2014年2月至2016年2月期间收治的150例脑炎继发癫痫患者为本次研究对象,并根据用药的不同分成3组,托吡酯组、卡马西平组以及丙戊酸钠组,每组患者各50例。托吡酯组给予托吡酯药物的口服治疗、卡马西平组给予卡马西平药物的口服治疗、丙戊酸钠组给予丙戊酸钠药物的口服治疗。分析三组患者的治疗效果以及不良反应发生情况,并进行对比。结果托吡酯组的有效率为82%;卡马西平组有效率为78%;戊酸钠组有效率为80%,三组患者的总有效率差异不显著,无统计学意义(P>0.05);托吡酯组、卡马西平组以及丙戊酸钠组患者的不良反应发生率分别为6.0%、20%、12%,卡马西平组不良反应发生率明显高于丙戊酸钠组和托吡酯组,丙戊酸钠组患者的不良反应发生率明显高于托吡酯组,三组差异对比有统计学意义(P<0.05)。结论对于脑炎继发癫痫患者的治疗而言,采用托吡酯、卡马西平以及丙戊酸钠均可达到理想的临床疗效,但卡马西平药物以及丙戊酸钠药物的不良反应发生率较高,托吡酯药物药物不良反应发生率较低,可以有效提升患者的安全性,应用价值较高。     

抗癫痫新药的治疗药物监测进展

抗癫痫新药包括:非尔氨酯、加巴喷丁、拉莫三嗪、左乙拉西坦、奥卡西平、托吡酯、氨己烯酸、唑尼沙胺、噻加宾等.自从左乙拉西坦、拉莫三嗪、奥卡西平、托吡酯引入国内以来,给医生提供了治疗癫痫的更多的选择,疗效与传统抗癫痫药物不相上下,保证新抗癫痫药物的合理使用,有效控制癫痫发作非常必要.     

左乙拉西坦联合卡马西平和托吡酯治疗难治性癫痫合并糖尿病分析

目的:探究左乙拉西坦联合卡马西平和托吡酯治疗难治性癫痫合并糖尿病的临床效果.方法:选取本院2015年4月～2016年4月收治的难治性癫痫合并糖尿病患者70例,分为观察组和对照组,每组35例,对照组实施卡马西平联合托吡酯治疗,观察组实施左乙拉西坦联合卡马西平和托吡酯治疗,比较两组临床治疗效果.结果:观察组癫痫发作次数低于对照组,观察组总有效率高于对照组,观察组不良反应发生率低于对照组,差异具有统计学意义(P<0.05).结论:在治疗难治性癫痫合并糖尿病中实施左乙拉西坦联合卡马西平和托吡酯,临床效果佳,能够有效减少癫痫发作次数,安全性高.     

不同类型抗癫痫药物对开颅手术患者术后早期高氨血症发病率的影响

目的：评价开颅手术患者应用左乙拉西坦、丙戊酸钠和卡马西平等3种不同抗癫痫药（AEDs）诱发高氨血症（AHA）的发生率、发作程度，并分析患者发生AHA的危险因素。方法：纳入2014年4月至2018年9月间在某院神经外科进行开颅手术的108患者，并将其随机分为左乙拉西坦组（n=36）、丙戊酸钠组（n=36）与卡马西平组（n=36）。3组患者术后分别口服左乙拉西坦片、丙戊酸钠片与卡马西平片进行癫痫预防治疗，在术前，手术当天，术后第1，3，7天检测并比较3组患者的血氨浓度、肝功能和凝血指标，评价3组患者术后AHA发生率、血氨浓度、血氨变化趋势及AEDs对患者肝功能和凝血功能的影响。根据术后患者是否发生AHA，将患者分为术后AHA组（n=70）与术后血氨正常组（n=38），比较2组患者的临床特征，评价患者发生AHA的危险因素。结果：左乙拉西坦组、丙戊酸组与卡马西平组分别有24（66.7%）例、29（80.6%）例及17（47.2%）例患者发生AHA，丙戊酸组患者AHA发生率显著高于卡马西平组（χ²=8.669，P=0.003）。丙戊酸钠组患者术后第3天和第7天血氨浓度及术后血氨的平均浓度均显著高于卡马西平组患者（P=0.023，<0.001，0.028）。术后第7天丙戊酸组患者ALT指标显著低于左乙拉西坦组与卡马西平组（均P<0.001）。影响患者术后发生AHA的危险因素包括：较低的年龄（t=2.061，P=0.042）与较高的术前血氨浓度（t=7.986，P<0.001）。AHA组患者术后总胆红素（t=3.788，P<0.001）、直接胆红素（t=3.329，P=0.001）和血清白蛋白（t=11.624，P<0.001）较术前显著降低，血浆凝血酶原时间显著延长（t=4.109，P<0.001）。而衡量急性肝炎的指标丙氨酸转氨酶没有显著变化（t=0.956，P=0.341）。结论：卡马西平对患者术后血氨浓度影响较小，是开颅手术患者的首选AEDs药物，而丙戊酸钠更适合肝脏氨基转移酶异常的患者。     

伴中央-颞区棘波儿童良性癫痫患者首次治疗分别使用丙戊酸钠、卡马西平、托吡酯的疗效比较

目的：比较丙戊酸钠、卡马西平、托吡酯作为伴中央-颞区棘波儿童良性癫痫（benign epilepsy with centro-temporal spikes,BECT）患儿首次治疗用药的疗效。方法：回顾性选取2019年2月—2022年2月本院收治的BECT患儿100例,依据用药方法不同分为丙戊酸钠组（40例）、卡马西平组（30例）、托吡酯组（30例）。比较各组临床疗效、认知功能、生活质量、首药治疗失败时间、药物不良反应事件发生情况、家长满意度。结果：三组总有效率、操作智商、语言智商、总智商评分、生活质量评分、家长满意度比较,差异无统计学意义（P>0.05）;卡马西平组首药治疗失败时间晚于丙戊酸钠组、托吡酯组（P<0.05）,且丙戊酸钠组患儿的首药治疗失败时间晚于托吡酯组（P<0.05）;丙戊酸钠组、卡马西平组药物不良反应事件发生率低于托吡酯组（P<0.05）,但丙戊酸钠组、卡马西平组药物不良反应事件发生率比较,差异无统计学意义（P>0.05）。结论：卡马西平、丙戊酸钠、托吡酯治疗BECT的疗效相当,均能够提升患者认知功能、生活质量、家长满意度,但与托吡酯相...     

卡马西平、托吡酯与丙戊酸钠缓释片对脑炎继发癫痫的疗效及不良反应观察

目的探究卡马西平、托吡酯以及丙戊酸钠缓释片对脑炎继发癫痫的治疗效果,并进行安全评价。方法脑炎继发性癫痫患者120例,分为三组,分别口服卡马西平、托吡酯以及丙戊酸钠缓释片进行治疗,以治疗效果和不良反应率作为评价指标,并进行统计学分析。结果托吡酯组的总有效率最高,卡马西平组最低,但三组差异无统计学意义（P〉0.05）;而托吡酯组的不良反应发生率最低,仅为10.0%,与其他两组相比,差异具有统计学意义（P〈0.05）。结论卡马西平、托吡酯以及丙戊酸钠缓释片对脑炎继发性癫痫的治疗效果旗鼓相当,但是托吡酯在临床应用中的不良反应率较低,因此托吡酯更加适用于癫痫的临床上治疗。     

2012-2014年南京地区34家医院抗癫痫药物利用分析

目的: 评价南京地区医院抗癫痫药的应用现状及趋势。方法: 对南京地区34家医院2012-2014年抗癫痫药的品种、用量、销售金额、用药频度等进行回顾性统计、分析。结果: 南京地区抗癫痫药销售金额逐年增加。各年度新型抗癫痫药销售金额均占抗癫痫药总销售金额的六成左右,DDDs所占比例从2012年的35.43%增长至2014年的45.53%。金额排序中丙戊酸钠各年度一直占据36%左右,稳居第一;新型抗癫痫药加巴喷丁、左乙拉西坦、奥卡西平销售金额逐年大幅增加,苯妥英钠、托吡酯年销售金额略有起伏。DDDs排序中丙戊酸钠以绝对优势稳居第一;新型抗癫痫药除托吡酯外用药频度均呈逐年增加趋势,而传统AEDs除丙戊酸钠外均逐年降低。结论: 南京地区抗癫痫药丙戊酸钠、奥卡西平选用倾向大,传统抗癫痫药丙戊酸钠在抗癫痫药中仍占据重要地位,新型抗癫痫药如奥卡西平、左乙拉西坦、拉莫三嗪、加巴喷丁等不良反应、耐受性、对肝药酶的影响性等优于传统抗癫痫药,市场前景良好。     

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。     

Use of Phenytoin,Phenobarbital Carbamazepine,Levetiracetam Lamotrigine and Valproate in Pregnancy and Breastfeeding: Risk of Major Malformations,Dose-dependency,Monotherapy vs Polytherapy,Pharmacokinetics and Clinical Implications

It is challenging to balance the fetal risks associated with the use of antiepileptic drugs (AEDs) against maternal and fetal risks of seizure worsening, and therefore it is very important to define and distinguish the possible risks entailed by different AEDs. This paper aims to undertake a comprehensive review regarding the possible risks of four classical (phenytoin, carbamazepine, phenobarbital, and valproate) and two newer (lamotrigine and levetiracetam) AEDs during pregnancy. The review focuses on major and organ-specific malformations, dose-dependent risks, mono vs polytherapy, and clinical pharmacokinetics. A discussion regarding the safety of AED use during breastfeeding is also provided.     

Differences between prescribed daily doses and defined daily doses of antiepileptics--therapeutic drug monitoring as a marker of the quality of the treatment

OBJECTIVE: Prescribed daily doses (PDDs) of antiepileptics (N03A ATC group) were recorded for drugs used in monotherapy or in combination therapy in the University Hospital in Ostrava, Czechia. Plasma levels were used as an indicator of the quality of treatment. METHOD: Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of PDDs and plasma levels. The study included 1,144 in-patients examined in the period 1993 - 2004. The differences in PDD were tested by Mann-Whitney-U-test. ATC/DDD index 2005 was used. Doses given in mono- and polytherapy were compared. RESULTS: Median PDDs in samples within the therapeutic range (in mg) in mono-/polytherapy were as follows (DDDs in parenthesis): carbamazepine 600/800 (1,000), clonazepam 2.0/2.0 (8), phenytoin 300/300 (300), ethosuximide -/1000 (1,250), lamotrigine 250/200 (300), phenobarbital -/200 (100), primidone 500/625 (1,250), topiramate -/300 (300), valproic acid 750/1,000 (1,500). Median PDDs in polytherapy with antiepileptics not analyzed for TDM were: gabapentin 900 (1,800), levetiracetam 1,500 (1,500), vigabatrin 1,500 (2,000). CONCLUSIONS: PDDs in monotherapy were similar or slightly lower than in combination therapy with an exception for lamotrigine, NS. The differences were significant in carbamazepine, p < 0.0001, and valproic acid, p < 0.001. Patients with plasma levels within the therapeutic range were usually treated with similar or slightly higher doses than the remainder. In polytherapy the PDDs were similar to DDDs in carbamazepine, ethosuximide, phenytoin, and topiramate in samples within the therapeutic range when difference +/- 20 per cent was considered as acceptable PDD of levetiracetam was also similar to actual DDD. In general plasma levels tended to be below the therapeutic range. The differences between PDD and DDD of antiepileptics have to be taken into account especially when utilization of different drugs is compared.     

传统抗癫痫药物与新抗癫痫药物对癫痫患者身体成分及脂代谢的影响

目的比较新抗癫痫药物与传统抗癫痫药物对患者身体成分及脂代谢的影响。方法收集我院癫痫患者112例。患者均服用新抗癫痫药(左乙拉西坦、拉莫三嗪、加巴喷丁)或传统抗癫痫药(丙戊酸钠、卡马西平、苯妥英钠)至少6个月。单一用药治疗73例,其中,服用左乙拉西坦片14例、丙戊酸钠15例、卡马西平20例、苯妥英钠24例。其余患者采用联合用药治疗。评估患者身体成分,包括体脂量、瘦干体质量(Lean dry mass,LDM),记录总体液量(Total body water,TBW)、细胞内液(Intracellular water,ICW)、细胞外液(Extracellular water,ECW)、基础代谢率(Basal metabolic rate,BM R),检测生化指标参数。结果左乙拉西坦组患者LDM较丙戊酸钠组患者降低(P<0.05),而其他身体成分与丙戊酸钠组、卡马西平组、苯妥英钠组比较差异无统计学意义(P>0.05)。与对照组比较,丙戊酸钠治疗组LDM及细胞外液较高;其余抗癫痫药物单一用药治疗组的身体成分与对照组比较差异无统计学意义(P>0.05)。传统抗癫痫药物单一治疗及联合新型药治疗组患者的LDM高于对照组(P<0.05),血清TC、三酰甘油也高于对照组(P<0.05)。结论抗癫痫药物对身体成分及脂代谢的影响作用可能影响其对癫痫患者(特别是身体成分发生变化的患者)的治疗反应。由于样本量的限制,以上结论需进一步大样本及前瞻性研究。     

Topiramate potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice

Topiramate (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in DBA/2 mice in a dose-dependent manner. Topiramate at dose of 2.5 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The degree of potentiation induced by topiramate was greatest for diazepam, phenobarbital and valproate, less for lamotrigine and phenytoin and not significant for carbamazepine and felbamate. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of the combination of all drugs+topiramate was more favourable than that of antiepileptics+ saline, with the exception of carbamazepine or felbamate+topiramate. Since topiramate did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interactions, in terms of total or free plasma levels, are not probable. However, the possibility that topiramate can modify the clearance from the brain of the anticonvulsant drugs studied cannot be excluded. In addition, topiramate did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, topiramate showed an additive effect when administered in combination with some classical anticonvulsants, most notably diazepam, phenobarbital, lamotrigine, phenytoin and valproate.     

抗癫痫药致胎儿畸形的研究进展

癫痫孕妇胎儿畸形的发病率为一般孕妇的2～3倍,而抗癫痫药为致胎儿畸形的主要原因,不仅传统的抗癫痫药,如苯妥英钠、苯巴比妥、卡马西平、丙戊酸钠可致胎儿畸形,新型抗癫痫药,如拉莫三嗪、托吡酯、奥卡西平、左乙拉西坦、氨己烯酸,经动物试验和病例报告证实,也能致胎儿畸形。使用抗癫痫药的孕妇胎儿畸形的发生率为4.2%～7.6%。抗癫痫药物联合应用的致畸率(6.0%～10.9%)高于单独应用的致畸率(3.7%～6.9%)。抗癫痫药所致胎儿畸形的主要临床表现为:颅面部畸形,指(趾)端发育不全,先天性心脏缺陷,小头畸形,神经管缺陷及出血倾向等。抗癫痫药致畸的机制可能和其致叶酸缺乏、阻断离子通道及神经元退行性变有关。处于妊娠和准备妊娠的癫痫患者应根据癫痫发作的类型、频次及其原因合理选择和使用抗癫痫药。用药期间应尽量采用单药治疗,将剂量调整为控制癫痫的最小剂量,加强血药浓度监测,补充叶酸和维生素K及做好产前检查,以减少或避免发生胎儿畸形。     

Neurodevelopment Following Exposure to Antiseizure Medications in Utero: A Review

Exposure in the womb to antiseizure medications and their potential impact on the brain of the developing child has long been researched. Despite this long period of interest, this review highlights that above the well-known risks associated with valproate exposure, there are more data required for conclusions regarding all other antiseizure medications. Limited experience with phenytoin and phenobarbital in monotherapy makes clearly defining the risk to later child postnatal functioning difficult, although the evidence of an impact is stronger for phenobarbital than for phenytoin. The widely prescribed lamotrigine is limited in its investigation in comparison to unexposed control children, and whilst it has been demonstrated to carry a lower risk than valproate for certain outcomes, whether it is associated with a more moderate impact on wider aspects of neurodevelopmental functioning is still to be understood. Data for levetiracetam, topiramate and oxcarbazepine are too limited to confidently draw conclusions for most neurodevelopmental outcomes. This slow accumulation of evidence impacts on the safest use of medications in pregnancy and makes counseling women regarding the risks and benefits of specific antiseizure medications difficult. Improved focus, funding, and research methodologies are urgently needed.     

A viewpoint on rational and irrational fixed-drug combinations

Introduction: Considering that there are around 30% of patients with epilepsy resistant to monotherapy, the use of synergistic combinations of antiepileptic drugs is of particular importance. This review shows most beneficial as well as irrational combined treatments both from an experimental and clinical point of view.

Areas covered: Preferably, experimental data derived from studies evaluating synergy, additivity, or antagonism by relevant methods, in terms of anticonvulsant or neurotoxic effects and pharmacokinetic data have been considered. Although there have been no randomized clinical trials on this issue, the clinical data have been analyzed from studies on considerable numbers of patients. Case-report studies have been not considered.

Expert commentary: The experimental data provide a strong support that co-administration of lamotrigine with carbamazepine is negative, considering the anticonvulsant and neurotoxic effects. Clinical reports do not entirely support this conclusion. Other experimentally documented negative combinations comprise lamotrigine+ oxcarbazepine and oxcarbazepine+ phenytoin. From the experimental and clinical point of view, a combination of lamotrigine+ valproate may deserve recommendation. Other most positive experimental and clinical combinations include carbamazepine+valproate, phenytoin+phenobarbital, carbamazepine+gabapentin, carbamazepine+topiramate, levetiracetam+valproate, levetiracetam+carbamazepine. Certainly, experimental data have some limitations (non-epileptic animals, acute administration of antiepileptic drugs) so all experimental recommendations need a careful clinical evaluation.     

The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs

A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research.