拉莫三嗪联合化风丹治疗初诊癫痫的疗效评价

目的探讨拉莫三嗪(LTG)联合化风丹治疗初诊癫痫病人的有效性和安全性。方法选取符合标准的80例新诊断癫痫病人,随机分为对照组和试验组,各40例,对照组给予单药LTG治疗;试验组给予LTG联合化风丹治疗,连续治疗12周后,检测治疗后病人的LTG血药浓度和视频脑电图(EEG)情况,记录治疗前后癫痫发作次数、持续时间、疗效及不良反应。结果对照组和试验组治疗总有效率分别为68.4%、87.2%,两组比较差异有统计学意义(P0.05);治疗后对照组和试验组LTG血药浓度和不良反应率,差异无统计学意义(P0.05);治疗后试验组癫痫发作次数、持续时间、痫性放电均低于对照组(P0.05)。结论 LTG联合化风丹治疗初诊癫痫病人可提高治疗有效率,减少癫痫发作次数,缩短癫痫持续时间。     

拉莫三嗪对抗外伤后晚期癫痫形成的临床研究

目的 评价早期应用拉莫三嗪(LTG)对急性脑外伤患者晚期癫痫(LPTE)发生率以及对认知功能恢复的影响.方法 具有癫痫高危因素的脑外伤患者175例,将175患者随机分为拉莫三嗪6个月组(A组,60例)、拉莫三嗪1个月组(B组,58例)与对照组(C组,57例).A组服用拉莫三嗪6个月;B组服用拉莫三嗪1个月;C组服用卡马西平1周.记录外伤后早期癫痫发作与晚期癫痫发生的人数以及意识清醒患者12个月时与1个月时的蒙特利尔认知评估(MoCA)量表评分.结果 A组、B组、C组晚期癫痫累计发生率分别为8.6%、7.2%、20.0%,A组、B组均显著低于C组(P=0.049).Cox比例风险回归显示LPTE的发生率与脑外伤严重程度具有显著相关性(r=3.657,95%CI 1.7～7.9).MoCA评分三组间无统计学意义(P>0.05),12个月评分拉莫三嗪两组高于C组(P<0.05),拉莫三嗪两组间无统计学意义(P>0.05).结论 早期小剂量拉莫三嗪干预,在一定程度上能有效对抗外伤后晚期癫痫的形成,且与卡马西平相比更有利于外伤后认知功能的恢复.     

小剂量丙戊酸联合拉莫三嗪治疗癫痫的疗效及安全性

目的探讨小剂量丙戊酸联合拉莫三嗪对老年癫痫患者的治疗效果及安全性。方法将80例老年癫痫患者随机分为对照组和研究组,每组40例;其中对照组患者给予丙戊酸治疗,研究组患者给予小剂量丙戊酸和拉莫三嗪联合治疗,24 w后对比两组患者的疗效、常规临床指标及血脂水平,比较两药血药浓度的相关性及不良反应发生率。结果与对照组相比,研究组患者的总有效率较高(P0.05)。治疗前后对照组患者血脂水平、腰臀比、体重指数(BMI)变化显著(P0.05),研究组患者各个指标均无明显变化(P0.05)。丙戊酸血药浓度与拉莫三嗪血药浓度呈正相关性(r=0.914,P0.05)。与对照组相比,研究组患者不良反应发生率明显降低(P0.05)。结论小剂量丙戊酸与拉莫三嗪的联合应用能够明显提高癫痫患者的治疗效果,维持体内血药浓度,提高用药安全性。     

拉莫三嗪治疗成人部分性癫痫发作的疗效评价

目的 评价拉莫三嗪治疗成人部分性癫痫发作的临床疗效.方法 将72例部分性癫痫发作患者随机分为两组,治疗组服用拉莫三嗪,对照组服用卡马西平,治疗前及治疗后第6个月复查脑电图,比较两组临床疗效、脑电图改善情况及药物不良反应.结果 治疗组临床疗效与对照组比较,差异无统计学意义（P＞0.05）;治疗组脑电图好转率高于对照组,差异有统计学意义（P＜0.05）.两组均未出现严重不良反应.结论 拉莫三嗪单药治疗成人部分性癫痫能较好地改善脑电图,且药物不良反应少.     

拉莫三嗪单药治疗新诊断成人癫痫临床研究

采用拉莫三嗪(LTG)单药治疗40例新诊断成人癫痫患者,并进行开放性自身对照研究,观察其临床疗效、用药剂量、安全性和不良反应.结果 LTG单药治疗总有效率为80%,其中完全控制率为67.5%,出现不良反应12.5%,包括皮疹、头痛、记忆力减退、月经紊乱等.认为LTG是一种有效、安全的抗癫痫药物.     

拉莫三嗪单药治疗老年癫痫患者的Meta分析

目的系统评价拉莫三嗪单药治疗老年癫痫患者的控制率及耐受性。方法用计算机对Cochrane癫痫组登记的数据库进行全面检索,并对相关的综述及参考文献进行追踪检索,观察癫痫控制率、副作用及其引发的退出率。结果共3篇中文文献和4篇英文文献最终纳入49个中心的随机对照试验,包括797例患者,4个涉及英国、法国、芬兰、挪威、克罗地亚等,治疗时间均在3个月以上。由于中文文献中1篇涉及脑卒中后癫痫患者的年龄被限定在50岁以上,2篇老年人群相关的亚组分析缺乏,因此排除这3篇中文文献;拉莫三嗪组与卡马西平组完成治疗人数呈现统计学意义上的异质性;拉莫三嗪组副作用引发的退出率显著低于卡马西平组(P0.05),但两组癫痫控制率、副作用发生率差异均不显著(P0.05)。结论拉莫三嗪单药治疗老年癫痫患者控制率和卡马西平相当,但具有较好的耐受性。     

拉莫三嗪治疗癫痫的有效性、安全性及HPLC法对拉莫三嗪药代动力学、血药水平的分析

目的分析拉莫三嗪(LTG)治疗癫痫病人的有效性、安全性及高效液相色谱法(HPLC)法对LTG药代动力学、血药水平的分析。方法收集2015年6月—2016年6月来我院就诊且符合纳入标准的癫痫病人70例,分析LTG的临床疗效、安全性及其血药水平与药代动力学关系。结果 LTG与内标物质的出峰时间分别为6.91 min和5.70 min,显示样品分离度良好,表明空白血浆中杂质对苯巴比妥与内标物质的定量检测无影响。通过其计算的药代动力学参数,可看到LTG血药水平在tmax=(2.01±0.42)h左右达到ρmax=(12.59±1.58)μg/mL。病人每日服用LTG剂量越大,其对应高血药水平范围例数就越多,表明体内LTG血药水平与剂量间存在较大相关性(F=72.24,P=0.0000)。同时服用LTG剂量60mg/d~200mg/d,LTG有效血药水平例数较多(86.04%)。LTG对4种类型癫痫病人控制率与有效率均较高,总体应答数为64例,应答率为91.43%(χ~2=5.395 3,P=0.249 1)。LTG血药水平在1μg/mL,1μg/mL~10μg/mL及10μg/mL区域,全面性与部分性发作癫痫病人有效率分别为80.00%,91.48%与84.62%(χ~2=2.213 1,P=0.330 7),表明LTG血药水平在1μg/mL~10μg/mL治疗癫痫临床疗效突出。在服药8周内70例病人出现不良反应有8例,但症状较轻微,总不良反应发生率为11.42%。结论采用LTG治疗癫痫病人疗效突出,合理的给药剂量可降低不良反应与毒副作用。HPLC法检测LTG血药水平具有高灵敏、简便经济的特点,通过准确观察其药代动力学变化,为病人提高个性化治疗方案,可提高疗效、安全性。     

拉莫三嗪治疗缺血性脑卒中继发癫痫40例临床研究

目的探讨拉莫三嗪（1amotrigine，LTC）治疗缺血性脑卒中继发癫痫的疗效，及其对癫痫发作间歇期痫样放电及α节律影响。方法将80例缺血性脑卒中继发癫痫病人随机分成2组，治疗组40例，逐步递增拉莫三嗪的剂量达控制剂量或目标剂量200mg/d，对照组40例，为常规治疗组，逐步递增卡马西平剂量达控制剂量或目标剂量0.9g/d，观察患者发作情况。两组病人分别在服药前及服药后第3个月查脑电图。结果治疗组控制20例，显效11例，有效7例，无效2例，总有效率95％；对照组控制14例，显效6例，有效7例，无效13例，总有效率67.5％；两组临床疗效差异有统计学意义。治疗前两组痫样放电及累及导联数比较无统计学意义，治疗3个月后治疗组较对照组减少更明显，差异有统计学意义。治疗组α节律无明显变化，时照组α波活动减少。结论 拉莫三嗪治疗缺血性脑卒中继发癫痫有较好的治疗效果，可使发作间歇期痫样放电减少，不影响脑电的背景活动。     

拉莫三嗪联合丙戊酸治疗不同类型癫痫病人的疗效观察

目的探讨拉莫三嗪联合丙戊酸治疗不同类型癫痫的临床疗效。方法选择2014年1月—2016年4月收治的癫痫病人154例为研究对象,根据发作类型分为部分性发作型(PS)组(55例)、继发性全面发作型(SGS)组(43例)、全面发作型(GS)组(35例)和Lennox Gastant综合征(LGS)组(21例)。所有病人均采用丙戊酸加拉莫三嗪进行治疗,至有效或不能耐受时停药,比较各组治疗6个月后总有效率、发作频率、炎症指标及不良反应发生率。结果治疗6个月后,临床总有效率PS组为89.09%、SGS组为86.05%、GS组为82.86%、LGS组为80.95%,组间比较差异无统计学意义(P0.05);治疗6个月后各组癫痫发作频率、血清白细胞介素-2(IL-2)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平较治疗前均显著降低,差异有统计学意义(P0.05),但组间比较差异均无统计学意义(P0.05);为期6个月的治疗期间,4组药物相关不良反应的发生率为7.79%,均未给予特殊处理自行缓解。结论拉莫三嗪联合丙戊酸治疗不同类型癫痫病人均可获得较满意的临床疗效,可显著改善炎症因子水平,且药物不良反应发生率低。     

拉莫三嗪治疗癫痫临床观察

对64例不同发作类型的癫痫患者给予常规治疗（对照组）或常规治疗＋拉莫三嗪治疗（观察组）。结果与对照组比较，观察组总有效率高，脑电图显著改善；不良反应无统计学差异。提示拉莫三嗪治疗癫痫有效、安全。     

Hyponatraemia associated with lamotrigine in cranial diabetes insipidus

We report the cases of two children with cranial diabetes insipidus who were treated with lamotrigine for seizures and who had accompanying changes in desmopressin requirements. Lamotrigine is a new anticonvulsant chemically unrelated to other existing antiepileptic drugs. Studies suggest it acts at voltage-sensitive sodium channels and also decreases calcium conductance. Both of these mechanisms of action are shared by carbamazepine, which can cause hyponatraemia secondary to inappropriate secretion of antidiuretic hormone. It is possible that the effect of lamotrigine on fluid balance in the cases described is also centrally mediated.     

Dress syndrome and fulminant hepatic failure induced by lamotrigine

Lamotrigine is a non-aromatic antiepileptic drug. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe idiosyncratic reaction to drugs, especially anti-epileptic drugs. Associated clinical features include cutaneous eruption, fever, multiple peripheral lymphadenopathies, and potentially life-threatening damage of one or more organs. We report a case of DRESS syndrome induced by lamotrigine presenting with a hypersensitivity syndrome and fulminant hepatic failure requiring liver transplant. A 21-year old female patient presented an episode of seizure with loss of conscience. CT and EEG studies performed were normal. Treatment with lamotrigine was prescribed. In the course of 30 days, the patient developed skin lesions, pruritus, cholestatic hepatitis, and systemic symptoms-fever, lymphadenopathies, extensive exfoliative erythematous maculopapular rash, and jaundice. Serologic and laboratory tests showed no other causes responsible for the clinical spectrum. Hematologic tests revealed peripheral eosinophilia. Fulminant hepatic failure was diagnosed and an orthotopic liver transplant was performed. Histologic sections of the ex-planted liver demonstrated submassive hepatic necrosis, with the remnant portal spaces and lobules showing a mixed inflammatory infiltrate with lymphocytes and eosinophils. Lamotrigine treatment has been associated with multiorgan failure, DRESS syndrome, acute hepatic failure, and disseminated intravascular coagulation. In conclusion, we suggest that these potentially fatal side effects should be considered in any patient with clinical deterioration following administration of this drug.     

Effects of lamotrigine on behavioral and cardiovascular responses to cocaine in human subjects

We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study employed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On each study day, placebo, lamotrigine 125 mg, or lamotrigine 250 mg was administered orally in the morning, followed 2 hours later by intranasal cocaine 120 mg/70 kg or placebo. Measurements of heart rate and blood pressure were acquired, and subjects responded to mood state questionnaires at predetermined time intervals. Cocaine alone produced increases in heart rate, blood pressure, and several measures of pleasurable mood and drug effects. Lamotrigine alone produced a mild relaxing effect. Lamotrigine pretreatment altered neither the physiological responses nor the subjective ratings of cocaine's pleasurable or aversive mood effects.     

拉莫三嗪对部分性发作癫痫患者认知功能及生活质量的影响

目的 评价拉莫三嗪(LTG)对部分性发作癫痫患者认知功能以及生活质量的影响.方法 对26例新诊断的部分性发作的癫痫患者随机分为两组,LTG组14例,给予LTG治疗,卡马西平(CBZ)组12例,给予CBZ治疗,在用药前及用药后16周进行认知功能评定及生活质量调查.认知功能评定包括数字广度,词语流畅、连线测验(A、B型)、Stroop字色干扰测验、威斯康星卡片分类测验(WCST)、延迟逻辑记忆、延迟视觉记忆、计算力、数字符号转换测验;生活质量调查采用癫痫患者生活质量评定量表-31(QOLIE-31). 结果癫痫患者应用LTG治疗16周后认知功能与用药前比较词语流畅性增加,A型、B型连线测验时间缩短,WCST正确数、分类数增加,持续错误、操作时间减少,数字符号转换测验增加,延迟逻辑记忆增加,延迟视觉记忆增加,均有统计学意义(t=3.043、-3.287、-2.543、3.167、3.028、-2.191、-3.216、3.061、3.036、3.021,P<0.01或P<0.05).两组治疗前后差值比较,LTG组比CBZ组Stroop读色时间减少,数字符号转换测验增加,计算力增加,差异均有统计学意义(t=3.167、2.142、2.101,P<0.01或P<0.05).QOLIE-31调查结果显示,与治疗前比较,LTG组和CBZ组治疗后综合生活质量、总体健康水平、认知功能、社会功能得分均增加(LTG组:t=3.321、2.462、3.294、3.512;CBZ组:t=3.314、3.149、3.294、3.202;P<0.01或P<0.05);LTG组与CBZ组治疗前后差值比较,认知功能、社会功能明显改善(t=2.257、2.140,均P<0.05),对发作的担心也减少(t=2.147、P<0.05). 结论 拉莫三嗪能够改善新诊断的部分性发作的癫痫患者认知功能,并提高生活质量.     

Prolonged anticonvulsant hypersensitivity syndrome related to lamotrigine in a patient with human immunodeficiency virus.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, potentially life-threatening allergic disorder, which is well described in relation to many aromatic anticonvulsants. Lamotrigine is a relatively new aromatic anticonvulsant agent that is thought to act on voltage-dependent sodium channels. Initially, it was licensed as add-on therapy for seizures inadequately controlled by other medications. However, its use has been broadened to other indications, including stand-alone therapy for seizures as well as for bipolar disorder. There is extensive experience with hypersensitivity syndromes related to phenytoin, carbomazepine, primidone, and phenobarbital, but fewer reactions have been reported to lamotrigine because of its relatively recent release. Patients with human immunodeficiency virus (HIV) have a higher rate of adverse reactions to many medications. It is unknown if they react more commonly to anticonvulsants such as lamotrigine. It is also unknown if the syndrome lias a tendency to be more severe or prolonged in such patients. The diagnosis of AHS may be particularly elusive in patients with HIV because its common features can easily be confused with an infectious etiology. We report the occurrence of a prolonged hypersensitivity syndrome likely related to lamotrigine in a 32-year-old female with HIV and review the literature regarding this condition.     

Fatal progressive hepatic necrosis associated with lamotrigine treatment: a case report and literature review

We present a case of fatal, progressive hepatotoxicity in a patient treated with lamotrigine. After presenting with a rash and fever, she developed elevated liver function tests and clinical sequelae of hepatic failure. The subacute course of her progressive liver damage is documented in serial liver biopsies. While her initial biopsy showed approximately 50% hepatocyte necrosis, her post mortem examination performed three weeks later displayed massive hepatic necrosis with extensive bile duct proliferation. Although she was taking other antipsychotics at the time, her clinical course best parallels other reports of lamotrigine-associated hepatotoxicity. Here we discuss not only the clinicopathologic findings of this case but also review the pertinent literature.     

Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy.

AIMS: To compare the efficacy and safety of lamotrigine and amitriptyline in controlling chronic painful peripheral neuropathy in diabetic patients. METHODS: A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 53). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time, each dose for 2 weeks, and lamotrigine orally, at doses of 25, 50 and 100 mg twice daily, each dose for 2 weeks, by optional titration were used. There was a placebo washout period for 2 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out. RESULTS: Good, moderate and mild pain relief were noted in 19 (41%), six (13%) and seven (15%) patients on lamotrigine and 13 (28%), five (11%) and 15 (33%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physicians global assessment, McGill pain questionnaire and Likert pain scale showed no significant difference between the treatments, although improvement with both treatments was seen from 2 weeks. Of the 44 adverse events reported, 33 (75%) were with amitriptyline, sedation being the commonest [in 19 (43%) patients]. Lamotrigine caused adverse events in 11 (25%), of which rash in three (7%) and elevations of creatinine in four (9%) were the most common. The preferred lamotrigine dose was 25 mg twice daily. CONCLUSIONS: As there are few differences between the two treatments in efficacy, lamotrigine 25 mg twice daily might be the first choice as it is associated with fewer adverse effects in our population.     

Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine

Animal studies show efficacy of intravenous lipid emulsion in the treatment of severe cardiotoxicity associated with local anesthetics, clomipramine, and verapamil, possibly by trapping such lipophilic drugs in an expanded plasma lipid compartment ("lipid sink"). Recent case reports describe lipid infusion for the successful treatment of refractory cardiac arrest caused by parenteral administration of local anesthetics, but clinical evidence has been lacking for lipid's antidotal efficacy on toxicity caused by ingested medications. A 17-year-old girl developed seizure activity and cardiovascular collapse after intentional ingestion of up to 7.95 g of bupropion and 4 g of lamotrigine. Standard cardiopulmonary resuscitation for 70 minutes was unsuccessful in restoring sustained circulation. A 100-mL intravenous bolus of 20% lipid emulsion was then administered, and after 1 minute an effective sustained pulse was observed. The patient subsequently manifested significant acute lung injury but had rapid improvement in cardiovascular status and recovered, with near-normal neurologic function. Serum bupropion levels before and after lipid infusion paralleled triglyceride levels. This patient developed cardiovascular collapse because of intentional, oral overdose of bupropion and lamotrigine that was initially refractory to standard resuscitation measures. An infusion of lipid emulsion was followed rapidly by restoration of effective circulation. Toxicologic studies are consistent with the lipid sink theory of antidotal efficacy.