左乙拉西坦治疗妊娠期癫痫疗效及胎儿安全性的Meta分析

目的：评价左乙拉西坦治疗妊娠期癫痫的疗效及其对胎儿的影响。方法：计算机检索Medline、Cochrane library、EMbase、CNKI、万方、维普、CBM数据库,收集有关左乙拉西坦治疗妊娠期癫痫疗效及胎儿安全性的队列研究和病例对照研究。依据纽卡斯-渥太华量表（NOS量表）对符合纳入标准的临床研究进行质量评价,并采用RevMan5.3进行Meta分析。结果：本研究共纳入11篇队列研究进行分析,采用NOS评分评估偏移风险,其中10项研究的得分均在7~9分。Meta分析结果显示,在妊娠期癫痫发作控制率方面,左乙拉西坦组低于丙戊酸钠组,差异有统计学意义（P<0.05）;而左乙拉西坦与拉莫三嗪、托吡酯、卡马西平或苯妥因单药治疗相比,两组间差异均无统计学意义（P>0.05）。在新生儿严重先天畸形发生率方面,左乙拉西坦组低于拉莫三嗪、托吡酯、丙戊酸钠、卡马西平或苯巴比妥组,差异均有统计学意义（P<0.05）;左乙拉西坦组与奥卡西平组相比,两组间差异无统计学意义（P>0.05）;左乙拉西坦单药治疗组明显低于多药治疗组（P<0.05）。左乙拉西坦对宫内死胎发生率的影响与拉莫三嗪、丙戊酸钠、卡马西平无明显区别（P>0.05）。结论：妊娠期癫痫患者服用左乙拉西坦单药治疗,其癫痫控制率可能低于丙戊酸钠,但与拉莫三嗪、托吡酯、卡马西平及苯妥因单药治疗疗效大致相当。在胎儿安全性结局方面,左乙拉西坦致畸性可能优于拉莫三嗪、托吡酯、丙戊酸钠、卡马西平及苯巴比妥,合并使用其他抗癫痫药物增加其致畸风险;左乙拉西坦对宫内死胎发生率的影响与拉莫三嗪、丙戊酸钠、卡马西平无明显区别。本文纳入研究均为队列研究,易受偏移风险的影响,故存在一定局限性。     

拉莫三嗪联合丙戊酸钠治疗外伤性癫癎复发疗效观察

目的 探讨丙戊酸钠治疗外伤性癫癎复发后,比较添加卡马西平或拉莫三嗪联合治疗外伤性癫癎效果.方法　采用开放性试验的方法对131例丙戊酸钠治疗外伤性癫癎复发患者,进行卡马西平或拉莫三嗪联合丙戊酸钠治疗,以治疗前3个月癫癎发作频度为对照,对治疗6个月后的疗效、不良反应及安全性进行自身对比观察.结果　应用卡马西平或拉莫三嗪联合丙戊酸钠治疗6个月后,患者发作频率均较用药前明显减少;发作频率减少≥50％的患者分别为72.6％和91.3％,差异有统计学意义(P＜0.01);卡马西平联合丙戊酸钠不良反应的发生率为37.1％,拉莫三嗪联合丙戊酸钠不良反应的发生率为8.7％.结论　拉莫三嗪联合丙戊酸钠治疗外伤性癫癎复发疗效确切,不良反应轻微.     

不同药物联合治疗老年脑卒中后癫痫发作效果观察

目的:探究奥卡西平与左乙拉西坦联合丙戊酸钠治疗老年脑卒中后癫痫发作患者的效果.方法:选取2018-10～2020-02安阳市人民医院120例老年脑卒中后癫痫发作患者,根据治疗方案不同分为两组,单药组57例给予丙戊酸钠,联合组63例给予丙戊酸钠、奥卡西平与左乙拉西坦,比较两组治疗效果、脑电控制情况、治疗前后认知功能(SP...     

286例新诊断成人癫痫患者的药物治疗

目的回顾性分析总结新诊断成人癫痫患者抗痫药物的规范化治疗、临床疗效及安全性。方法对286例新诊断成人癫痫患者采用规范化药物治疗,于治疗24个月后评价临床疗效、单药治疗保留率及安全性。结果 286新诊断成人癫痫患者中224例(78.3%)采用单药治疗,62例(21.7%)采用了2种药物联合治疗。24个月总无发作率65.7%,有效率31.1%,无效率3.2%。单药治疗保留率卡马西平58.3%、拉莫三嗪77.8%、奥卡西平63.0%、丙戊酸钠61.3%、苯妥英钠47.6%、托吡酯46.7%、左乙拉西坦66.7%。结论临床规范化使用抗癫痫药物治疗可获得满意临床疗效,安全性高,显示了较好的临床实用性,宜于推广应用。     

抗癫痫药相关低钠血症

多种抗癫痫药与低钠血症有关,其中以卡马西平、奥卡西平和艾司利卡西平最为常见,涉及的其他抗癫痫药还有丙戊酸、左乙拉西坦、拉莫三嗪和拉考沙胺等。抗癫痫药相关低钠血症的大多数患者症状轻微,但是严重的急性或慢性持续性低钠血症可导致癫痫、昏迷等,甚至导致死亡。抗癫痫药物导致低钠血症的发生机制并未完全明确,目前认为可能与抗利尿激素...     

60例癫痫患者治疗的疗效分析

目的比较丙戊酸钠与左乙拉西坦治疗癫痫的疗效。方法将60例癫痫患者完全随机分为丙戊酸钠组30例,左乙拉西坦组30例。丙戊酸钠组应用丙戊酸钠治疗,左乙拉西坦组应用左乙拉西坦治疗,观察治疗效果。结果丙戊酸钠组30例癫痫患者治疗后无效4例、有效20例、完全控制5例、加重1例、总有效率25例(83.4%);左乙拉西坦组30例癫痫患者治疗后无效3例、有效18例、完全控制6例、加重3例、总有效率24例(80%)。两组总有效率的比较差异无统计学意义,即总有效率差异无显著性。结论丙戊酸钠和左乙拉西坦均是相对有效的抗癫痫治疗药物。     

丙戊酸钠对难治性癫痫患者神经因子及炎性因子水平的影响

目的 观察丙戊酸钠对难治性癫痫患者神经因子及炎性因子水平的影响。方法 选取2019年1月—2022年6月福州市第一医院收治的难治性癫痫患者83例,采用随机数字表法分为丙戊酸钠组(n=42)和左乙拉西坦组(n=41)。在常规对症支持治疗基础上,左乙拉西坦组患者给予左乙拉西坦治疗,丙戊酸钠组患者给予丙戊酸钠治疗,2组均持续治疗6个月。比较2组患者的临床疗效,治疗前及治疗2、4、6个月后的认知状态及神经功能缺损程度,治疗前后的神经因子、炎性因子水平及不良反应。结果 丙戊酸钠组患者治疗总有效率为97.62%,高于左乙拉西坦组的78.05%(χ²=7.499,P=0.006)。丙戊酸钠组患者治疗4、6个月后的简易智能精神状态表(MMSE)评分均高于左乙拉西坦组(P<0.01);丙戊酸钠组患者治疗6个月后神经功能缺损评分(NIHSS)低于左乙拉西坦组(P<0.01)。治疗6个月后,2组患者神经元特异性烯醇化酶(NSE)、髓鞘碱性蛋白(MBP)水平和肿瘤坏死因子-α(TNF-α)、白介素-2(IL-2)、白介素-6(IL-6)水平均较治疗前降低,且丙戊酸钠组低于左乙...     

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。     

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。     

卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能和骨密度的影响分析

目的探究卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能、骨密度的影响。方法92例成人癫痫患者作为研究对象,随机分为左乙拉西坦组与卡马西平组,各46例。左乙拉西坦组采用左乙拉西坦治疗,卡马西平组采用卡马西平治疗。比较两组患者治疗前及治疗6个月后认知功能[语言智商(VIQ)、操作智商(PIQ)、总智商(FIQ)]评分、骨密度(腰椎、股骨大转子、股骨颈)变化情况。结果治疗6个月后,两组患者VIQ、PIQ、FIQ评分均较治疗前显著提升,且左乙拉西坦组患者VIQ评分(101.2±3.1)分、PIQ评分(108.1±2.3)分、FIQ评分(105.2±1.8)分均明显高于卡马西平组的(95.1±2.8)、(94.1±2.0)、(93.5±1.6)分,差异有统计学意义(P<0.05)。治疗6个月后,卡马西平组患者腰椎、股骨大转子、股骨颈骨密度均较治疗前显著下降,且明显低于卡马西平组,差异有统计学意义(P<0.05);左乙拉西坦组治疗6个月后腰椎、股骨大转子、股骨颈骨密度与治疗前比较差异无统计学意义(P>0.05)。结论左乙拉西坦与卡马西平治疗成人癫痫,左乙拉西坦更能明显提升患者认知功能,且对患者骨密度无影响。     

Serum concentrations of topiramate in patients with epilepsy: influence of dose,age, and comedication

Topiramate is a new antiepileptic drug (AED) approved as add-on therapy. Previous studies have shown that topiramate has only a limited effect on other AEDs, but its own metabolism can be induced by enzyme-inducing drugs. The aim of this study was to investigate the influence of topiramate dose, age, and comedication, especially of carbamazepine, phenytoin, phenobarbital, oxcarbazepine, lamotrigine, and valproic acid (VPA) on topiramate serum concentrations in patients with epilepsy. In total, 480 samples of 344 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. The topiramate serum concentration in relation to topiramate dose per body weight (level-to-dose ratio) was calculated and compared for patients receiving topiramate monotherapy and for patients receiving topiramate plus one other AED. Analysis of covariance (using age as covariate) showed that comedication had a highly significant influence on the topiramate serum concentrations. Regression analysis including all 480 samples confirmed that in combinations with phenytoin, carbamazepine, phenobarbital, and oxcarbazepine, the topiramate concentrations were significantly lower compared with topiramate monotherapy, whereas VPA and lamotrigine had no significant influence. Moreover, regression analysis indicated that primidone and methsuximide lowered topiramate concentrations, whereas gabapentin, bromide, and sulthiame did not. In addition to comedication, the patient's age was significantly correlated with topiramate clearance. In accordance with the results of previous studies, these results indicated that infants and children had lower topiramate concentrations than adults receiving the same topiramate dose per body weight. Comedication and age should be considered in adjusting topiramate dosage. Determination of topiramate serum concentrations may be useful, especially when enzyme-inducing drugs are withdrawn or added.     

Amelioration of erectile dysfunction following a switch from carbamazepine to oxcarbazepine: recent clinical experience

Oxcarbazepine is an antiepileptic drug (AED) indicated for use as monotherapy and add-on therapy in adults and children 4 years of age and older. Despite being structurally related to carbamazepine, oxcarbazepine differs substantially in its pharmacokinetic and safety profile; oxcarbazepine has a much lower risk of pharmacokinetic drug-drug interactions than carbamazepine. Carbamazepine has also been shown to induce the hepatic synthesis of sex hormone-binding globulin, thus reducing free serum testosterone levels and possibly causing erectile dysfunction (ED) in some men; these effects have not been observed with oxcarbazepine. This paper provides a discussion of recent clinical experience with men who presented in private clinical practice with complaints of ED while being treated with carbamazepine for seizure disorders. The four illustrative case studies presented in this report suggest that switching AED treatment from carbamazepine to oxcarbazepine in men with epilepsy can reduce the ED side effects observed with carbamazepine.     

Amelioration of erectile dysfunction following a switch from carbamazepine to oxcarbazepine: recent clinical experience

ABSTRACT

Oxcarbazepine is an antiepileptic drug (AED) indicated for use as monotherapy and add-on therapy in adults and children 4 years of age and older. Despite being structurally related to carbamazepine, oxcarbazepine differs substantially in its pharmacokinetic and safety profile; oxcarbazepine has a much lower risk of pharmacokinetic drug–drug interactions than carbamazepine. Carbamazepine has also been shown to induce the hepatic synthesis of sex hormone-binding globulin, thus reducing free serum testosterone levels and possibly causing erectile dysfunction (ED) in some men; these effects have not been observed with oxcarbazepine. This paper provides a discussion of recent clinical experience with men who presented in private clinical practice with complaints of ED while being treated with carbamazepine for seizure disorders. The four illustrative case studies presented in this report suggest that switching AED treatment from carbamazepine to oxcarbazepine in men with epilepsy can reduce the ED side effects observed with carbamazepine.     

Selection criteria for the clinical use of the newer antiepileptic drugs

In recent years, several new antiepileptic drugs (AEDs) have been licensed: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. These drugs have proven efficacy as add-on therapy in patients with difficult-to-treat partial epilepsy, as 20-50% of patients treated in add-on trials experienced a seizure reduction of >or=50%. Relatively few trials have been conducted to evaluate these drugs as monotherapy for patients with newly diagnosed epilepsy. In the monotherapy trials that have been conducted, the newer drugs were often as efficacious as conventional drugs, and their tolerability was often better. However, the methodology of these trials can be criticised. Because of the relative lack of robust data for the newer agents, the conventional drugs have thus far maintained their status as first-line monotherapy. However, when first-line monotherapy fails, an alternative drug has to be chosen from the available conventional and newer drugs. This article aims to give detailed background information on the newer AEDs in order to enable physicians to make a rational choice from the available drugs for individual patients. Data are provided for the different newer AEDs on mechanisms of action; efficacy in refractory partial epilepsy, newly diagnosed epilepsy in adults and generalised seizure types; adverse effects; pharmacokinetics; and use in special patient categories.     

The tolerability of lamotrigine in elderly patients with epilepsy

OBJECTIVE: To determine the tolerability of lamotrigine in elderly patients with epilepsy. DESIGN: Pooled data from 13 lamotrigine clinical trials. SETTING: Multicentre clinical trials conducted in primary care and neurology practices. PARTICIPANTS: 208 elderly patients (aged > or = 65 years) were identified: 146 lamotrigine-treated patients, 53 carbamazepine-treated patients and 9 phenytoin-treated patients. INTERVENTIONS: Extent of exposure, incidence of drug-related adverse events, serious adverse events and study withdrawals were examined. RESULTS: The median duration of exposure for lamotrigine monotherapy and add-on therapy was 24.1 and 47.4 weeks, respectively. The median daily dosage of lamotrigine was 100 mg for monotherapy (range 75 to 500 mg) and 300 mg for add-on therapy (range 25 to 700 mg). Overall, the incidence of drug-related adverse events was lower for lamotrigine than comparator drugs: 49% (72/146) for lamotrigine compared with 72% (38/53) for carbamazepine (p = 0.006), and 89% (8/9) for phenytoin (p = 0.035) although patient numbers in each treatment group were not comparable. Patients receiving lamotrigine reported incidences of somnolence (p = 0.012), rash (p = 0.034), and headache (nonsignificant) that were one-half the incidence reported with carbamazepine monotherapy. Rash was the most common reason for study withdrawal: 4% (6/146) lamotrigine, 17% (9/53) carbamazepine and 0% phenytoin. Seven (5%, 7/146) lamotrigine-treated patients, 4 (8%, 4/53) carbamazepine-treated patients and 1 (11%, 1/9) phenytoin-treated patient experienced drug-related serious adverse events. CONCLUSION: Lamotrigine, used in the currently prescribed adult dosage regimen, was well tolerated in elderly patients with epilepsy.     

Oxcarbazepine for epilepsy--a useful new choice?

Oxcarbazepine* (Trileptal-Novartis), an anti-epileptic first marketed in the UK in 2000, is licensed for use both as adjunctive (add-on) therapy and as monotherapy for adults and children aged 6 years or over with partial-onset epileptic seizures, with or without secondary generalisation. The company claims that oxcarbazepine has "comparable efficacy" to carbamazepine with "greater tolerability", and causes "fewer withdrawals due to side effects compared to most established antiepileptic drugs". Here we discuss the place of oxcarbazepine in the treatment of epilepsy.     

Serum concentrations of Levetiracetam in epileptic patients: the influence of dose and co-medication

Levetiracetam (LEV) is a new antiepileptic drug approved as add-on therapy. Previous studies indicated that LEV has no relevant interactions with other antiepileptic drugs. The aim of this study was to investigate the influence of LEV dose, age, and co-medication on the serum concentration of LEV. In total, 363 samples of 297 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. A patient was considered twice only if his co-medication had been changed. The LEV serum concentration in relation to LEV dose/body weight [level-to-dose ratio, LDR, (microgram/mL)/(mg/kg)] was calculated and compared for the most frequent drug combinations. Analysis of covariance (using age as covariate) carried out on the log-transformed data showed that co-medication had a highly significant (P < 0.001) effect on LEV serum concentrations. The median LDR of LEV was 0.32 for LEV + phenytoin, 0.32 for LEV + carbamazepine, 0.34 LEV + oxcarbazepine, 0.45 for LEV + lamotrigine, 0.46 for LEV + phenobarital, 0.52 for LEV monotherapy, 0.53 for LEV + valproic acid, and 0.54 LEV + valproic acid + lamotrigine. In co-medication with phenytoin (P < 0.001), carbamazepine (P < 0.001), and oxcarbazepine (P < 0.004), the LDR of LEV was significantly lower than it was with LEV monotherapy, whereas the LDR of LEV of patients on co-medication with valproic acid or lamotrigine did not differ significantly from the LDR of LEV of patients on LEV monotherapy (P > 0.05). Regression analysis including all 363 samples confirmed that other drugs (e.g., phenytoin, carbamazepine) lower LEV concentrations. In addition to co-medication, age had a significant effect on clearance of LEV. Children had lower LEV concentrations than adults on the same LEV dose per body weight. In contrast to other studies, our data point out that other enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine) can moderately decrease LEV serum concentrations (by 20-30%). However, our observations should be confirmed by prospective pharmacokinetic studies.     

Efficacy and Tolerability of Antiepileptic Drugs in Patients with Focal Epilepsy: Systematic Review and Network Meta‐analyses

Several newer antiepileptic drugs (AEDs) have been introduced into clinical practice, offering choices for individualizing the treatment of epilepsy since AEDs have different efficacy and tolerability profiles. In particular, questions exist regarding which AEDs are the best options for the monotherapy of focal epilepsy. Is carbamazepine (CBZ), which is considered the standard treatment for focal epilepsy, still the best option for monotherapy of focal epilepsy, despite the emergence of new AEDs? In this systematic review, we compared the relative tolerability of all available AEDs for monotherapy of all types of epilepsy as well as their efficacy in the monotherapy of focal epilepsy. In addition, we compared CBZ with other AEDs for the monotherapy of focal epilepsy. We performed a search of the MEDLINE/PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for randomized controlled clinical trials. To compare the relative efficacy and tolerability of the AEDs, we performed network meta‐analyses using a Bayesian random‐effects model. Sensitivity analyses were conducted to determine the robustness of the results. A total of 65 studies were included in this review, composing 16,025 patients. Clobazam, levetiracetam, lamotrigine, oxcarbazepine, sulthiame, topiramate, and valproate had the best efficacy profiles and demonstrated no evidence of superiority or inferiority compared with CBZ. However, CBZ showed the greatest risk of patient discontinuation due to intolerable adverse reactions, whereas lamotrigine had the best safety profile and an 81% probability of being the best for the tolerability outcome of patient withdrawals from the study due to intolerable adverse reactions, followed by sulthiame (60%) and clobazam (51%). The newer AEDs—levetiracetam, lamotrigine, oxcarbazepine, sulthiame, and topiramate—should be considered for monotherapy of focal epilepsy because they were demonstrated to be as effective as the older ones (CBZ, clobazam, and valproate) for the treatment of focal epilepsy and were more tolerable. Lamotrigine was the AED with the best tolerability profile, suggesting that it may be the best option for the treatment of focal epilepsy in children and adults.     

几种新癫痫药分别联合丙戊酸钠治疗难治性癫痫的对比

目的：探讨部分难治性癫痫（RE）在添加拉莫三嗪（LTG）或奥卡西平（OXC）或托吡酯（TPM）联合丙戊酸钠（VPA）治疗的临床疗效。方法累积收集2009年1月~2014年1月符合标准的212例难治性部分性癫痫患者,对照治疗3个月前癫痫发作频度,并对治疗2年结束后的疗效、不良反应（ADR）及安全性和脑电图进行自身分析对比。结果患者应用LTG或OXC或TPM联合VPA治疗RE 2年结束后,患者发作频率均比用药前明显减少,患者治疗结束后的总有效率分别为89%、88.5%、78.1%, ADR的发生率分别为9.6%、19.2%、21.9%,脑电图总的好转率分别为89.9%、78.5%、76.9%。结论 LTG或OXC或TPM联合VPA治疗RE患者的疗效确切,耐受性好,安全性高, ADR轻。