汉族人拉莫三嗪相关过敏反应与HLA-B*1502的相关性

目的研究在汉族人中拉莫三嗪相关过敏反应是否与HLA-B*1502有相关性。方法对在郑州人民医院诊断为癫痫的患者在服用拉莫三嗪前进行HLA-B*1502测定,将服用拉莫三嗪12周后出现过敏反应者作为实验组,未出现过敏反应者作为对照组1,服用其他非芳香族抗癫痫药物出现过敏反应者为对照组2,检测对照组2的HLA-B*1502阳性率,对3组间HLA-B*1502的阳性率进行比较。结果实验组HLA-B*1502的阳性率为41.86%,对照组1为14.02%,对照组2为13.33%.实验组阳性率高于对照组1(χ2=13.86,P<0.05)及对照组2(χ2=6.83,P=0.009),对照组1与对照组2比较差异无统计学意义(χ2=0.009,P=0.924)。结论HLA-B*1502可能与汉族人拉莫三嗪相关过敏反应相关。     

拉莫三嗪与奥卡西平单药治疗成人新诊断局灶性癫痫的长期疗效及安全性比较

目的 比较拉莫三嗪(LTG)和奥卡西平(OXC)单药治疗成人新诊断局灶性癫痫的长期疗效、耐受性和安全性。方法 收集本院癫痫专病门诊新诊断的局灶性癫痫,随机分成OXC组和LTG组,根据临床情况调整剂量,OXC最大剂量1200 mg/d,LTG最大剂量300 mg/d,至少随访3年,评估二种药物单药治疗成人新诊断局灶性癫痫无发作率、保留率及不良反应。结果 2009年6月-2016年6月符合入组标准146例,其中OXC组74例,LTG组72例,2组1年无发作率分别为35.1%和51.3%(χ2=3.9,P=0.047),3年无发作率分别为21.6%和40.2%(χ2=5.96,P=0.015),LTG组总体无发作率高于OXC组(P<0.05); OXC组和LTG组1年保留率分别为59.5%和69.4%(χ2=1.59,P=0.208),3年保留率分别为44.6%和51.4%(χ2=0.68,P=0.411),LTG组总体保留率亦高于OXC组,但无明显差异(P>0.05)。OXC组和LTG组最常见的不良反应均为皮疹(6.8% vs. 8.3%)。结论 LTG单药治疗新诊断成人局灶性癫痫的长期无发作率高于OXC,两者不良反应较轻,有较好的安全性。     

RP-HPLC法同时测定人血清中4种抗癫痫药的浓度

目的：建立同时测定人血清中拉莫三嗪(LTG)、苯巴比妥(PB)、苯妥英(PHT)和卡马西平(CBZ)浓度的高效液相色谱法。方法血清样品经甲醇沉淀蛋白后直接进样测定。色谱柱采用Waters Symmetry C18柱(250 mm×4.6 mm,5μm),流动相为甲醇-水(55∶45),检测波长235 nm。结果 LTG、PB、PHT和CBZ的线性范围分别是1.56~50、3.13~100、2.19~70、1.09~35μg/ml,平均回收率均>98%。结论本方法操作简便,结果准确,适用于临床治疗药物监测。     

Efficacy and tolerability of lamotrigine in Juvenile Myoclonic Epilepsy in adults: A prospective,unblinded randomized controlled trial

PurposeControlled randomized studies recommending the clinical use of lamotrigine in adult populations with the diagnosis of Juvenile Myoclonic Epilepsy are still lacking. To compare the efficacy and tolerability of lamotrigine versus valproate in adult patients with JME.MethodsThis was a prospective, randomized, controlled, pragmatic, long-term and open-label treatment trial. Patients were randomized to use valproate or lamotrigine. The primary end points of the study were: (1) time from randomization to treatment failure (withdrawal); (2) time from randomization to seizures remission. Secondary ending points were: (1) frequency of clinically important adverse events and (2) change in the QOLIE-31 after randomization. The definition of seizure remission was based on disappearance of all seizure types and EEG discharges.ResultsWe found that the time to withdraw treatment after randomization was not significantly different in lamotrigine and valproate groups. Long-term seizures freedom was equal in the both groups of the trial; only 8 (19.1%) patients randomized to lamotrigine and 6 (19.4%) randomized to valproate were not seizure free after 4 months of treatment. Between 17.03% (lamotrigine) and 35.3% (valproate) of patients reported adverse reactions at some point in the intention-to treat study (p = 0.07). All subscales of the QOLIE-31 questionnaire, except that related to side effects of medication, improved more than 5 points with respect to baseline period in both groupsConclusionLamotrigine is effective in adult patients with Juvenile Myoclonic Epilepsy and better tolerated than valproate, although the incidence of idiosyncratic reactions could be a cause of concern.     

拉莫三嗪联合MECT治疗难治性抑郁症的临床对照研究

目的:观察拉莫三嗪联合MECT治疗难治性抑郁症的疗效;方法:选取符合入组条件的难治性抑郁症门诊或住院患者47名,采取病例组对照的方法,运用拉莫三嗪联合MECT治疗,观察期限6周。入组后拉莫三嗪1周后加至200mg/d;自第2周始,每周3次,隔日治疗,均接受总数8次的MECT治疗。对照组选取住院符合难治性的抑郁症患者39例,采取拉莫三嗪联合假性MECT治疗的方法,药物剂量同观察组。两组的效果评估采取精神科医生精神现况检查评估、患者及家属自我体验效果结合抑郁自评量表(SDS)和17项版本的汉密尔顿抑郁量表减分率共同评价。结果:研究组完成观察数44例。终止观察3例,脱落率6.38%,其中因出现皮疹终止观察2例,自行停止观察1例。对照组完成观察数37例,脱落2例,脱落率5.13%;两组的脱落率和副反应比较差异没有显著性(P0.05)。研究结果显示,两组分别在精神科现况检查(PSE)、患者/家属体验、SDS和汉密尔顿抑郁量表(17项版本)的评定结果中,"痊愈"项目的两组间比较均显示出了差异性(χ~2=6.11,9.01,10.23,8.24;P0.01)。患者/家属体验评估中两组间的"有效"指标比较,差异有显著性(χ~2=2.66,P0.05);余项目的两组间比较没有显示出差异性(P0.05)。结论:拉莫三嗪联合MECT治疗难治性抑郁症安全有效,可以作为候选方案之一;单用拉莫三嗪治疗难治性抑郁症疗效尚不确定。     

拉莫三嗪和丙戊酸钠联合治疗儿童难治性癫痫临床观察

目的了解丙戊酸钠和拉莫三嗪联合治疗小儿难治性癫痫的疗效及安全性。方法收集难治性儿童癫痫患者29例,进行拉莫三嗪联合丙戊酸钠治疗,以治疗前3个月癫痫发作频度为对照,对治疗后12个月内的疗效、不良反应、耐受性及安全性进行自身对比研究。结果全面性发作7例,部分性发作12例,部分继发全面发作8例,Lennox Gastaut综合征2例。完全控制5例,显效4例,有效7例,总有效率48.3%。治疗前后发作频率减少有显著性差异（P〈0.01）。不良反应的发生率为17.2%（5/29）。常见的不良反应为皮疹、乏力、头晕、头痛、恶心、食欲下降。结论拉莫三嗪和丙戊酸钠联合应用为一种有效,安全而经济的治疗小儿难治性癫痫的方法,值得临床应用。     

Comparison of plasma,saliva, and hair lamotrigine concentrations

BackgroundIn some clinical situations (pregnancy, aging, drug resistance, toxicity), measurements of lamotrigine plasma levels may be reliable. Limited studies indicate that saliva and hair could be alternative sources for monitoring lamotrigine therapy. The drug content in hair can also be used to assess the history of drug therapy and to ascertain long-term patient compliance. The aims of this study were to 1) determine the correlations among plasma, saliva, and hair lamotrigine concentrations, 2) evaluate saliva as an alternative matrix for monitoring drug levels and 3) evaluate hair as a source of information on adherence to antiepileptic treatment and on the correlation of hair concentrations with clinical outcomes in patients with epilepsy.MethodsPlasma, saliva, and hair lamotrigine concentrations were measured by liquid chromatography–tandem mass spectrometry in positive ionization mode. The study group (n = 85) was recruited among the epileptic patients at the Institute of Psychiatry and Neurology, Warsaw, Poland.ResultsPlasma concentrations were not influenced by sex, age, or the concomitant use of other antiepileptic drugs. Lamotrigine saliva and plasma concentrations were strongly correlated (r = 0.82, p < 0.001). Lamotrigine hair concentrations were correlated with the plasma concentrations (r = 0.53, p < 0.001) and daily dose in mg/kg (r = 0.23, p = 0.024). The analysis revealed no significant correlation between lamotrigine hair levels and the number of seizures in the previous 3 months (r = -0.1, p > 0.05).ConclusionsThe lamotrigine saliva concentration is strongly correlated with its plasma level, and saliva can be used as an alternative matrix to plasma for monitoring. Lamotrigine can also be successfully measured in hair, and the drug levels in hair tend to be correlated with the levels in plasma. However, lamotrigine levels in hair may not correspond to clinical outcomes (i.e., seizure episodes).     

拉莫三嗪对大鼠脑缺血再灌注损伤的神经保护作用

目的:探讨拉莫三嗪(lamotrigine,LTG)对脑缺血再灌注损伤的神经细胞的保护作用。方法:Pulsinelli四血管闭塞法建立大鼠全脑缺血再灌注损伤模型,观测LTG对脑缺血再灌注损伤后脑细胞外液谷氨酸含量的动态变化,脑组织的病理改变和神经细胞凋亡。结果:(1)再灌注组、治疗组谷氨酸基础水平与对照组基本相同,缺血后迅速升高,再灌注30min达高峰,其后逐渐下降。再灌注组在30～330min内显著高于对照组(P<0.05),治疗组在30～330min内显著高于对照组,但低于再灌注组(P<0.05)。(2)TUNEL法发现治疗组凋亡细胞较再灌注组明显减少(P<0.05)。结论:脑缺血再灌注损伤后,早期使用LTG治疗,明显减轻脑组织中兴奋性氨基酸含量,增加神经元细胞的存活率。     

Mood stabilizing drugs lamotrigine and olanzapine increase expression and activity of glutathione s-transferase in primary cultured rat cerebral cortical cells

The anticonvulsant lamotrigine and atypical antipsychotic olanzapine, as therapeutic alternative mood stabilizing drugs to lithium and valproate, are well-tolerated maintenance treatments for bipolar disorder. Previous studies in our laboratory showed that both lithium and valproate increased expression of glutathione s-transferase (GST)-M1 subtype in primary cultured rat cerebral cortical cells. GST conjugates glutathione, the major antioxidant in brain, with a variety of oxidized products to form non-toxic and excretable products, and plays an important role in cellular protection against oxidative stress. The purpose of the present study is to determine whether lamotrigine and olanzapine also regulate GST-M1. Using immunoblotting analysis and spectrophotometric assay, we examined the effect of lamotrigine or olanzapine on GST-M1 protein levels and GST enzyme activity in primary cultured rat cerebral cortical cells. We found that chronic treatment with lamotrigine or olanzapine increased both GST-M1 protein levels and GST enzyme activity. These results suggest that GST-M1 may contribute a significant component to the treatment of bipolar disorder with mood stabilizing drugs.