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。     

多个癫痫相关基因多态性与拉莫三嗪治疗儿童癫痫血药浓度的相关性

  目的  拉莫三嗪是儿童癫痫的一线治疗药物,其血药浓度与临床疗效个体差异较大,药效学和药动学通路多个相关基因突变可能是个体差异大的原因,本研究探讨代谢酶UGT1A4,转运体OCT1与ABCB1,受体SCN1A基因多态性与拉莫三嗪治疗儿童癫痫稳态血药浓度的相关性。   方法  于2018年1月—2019年6月纳入杭州市第一人民医院单用拉莫三嗪治疗的49例癫痫儿童,采集拉莫三嗪治疗达稳定剂量超过7 d以上患儿的稳态谷浓度血浆,使用高效液相色谱法测定拉莫三嗪血药浓度,直接测序法分析代谢酶UGT1A4(rs2011425)、转运体OCT1(rs628031)、ABCB1(rs1045642与rs1128503)和受体SCN1A(rs3812718)的基因分型。采用Kruskal-Wallis H检验或Mann-Whitney U检验探究不同基因分型与拉莫三嗪(LTG)血药浓度及标准化血药浓度相关性[即LTG血浆药物浓度除以每日每千克体重的服药剂量, CDR,(μg/mL)/(mg/kg)],P < 0.05为具有显著相关性。   结果  转运体OCT1 rs628031与拉莫三嗪CDR具有显著相关性,其中AA+AG携带者CDR值显著高于GG携带者,分别是1.27(1.03, 2.20)和0.69(0.57, 1.02),P=0.002;但其他基因型与CDR值无显著相关性。   结论  CT1 rs628031基因突变可能是拉莫三嗪血药浓度和临床疗效个体差异大的重要因素。      

Lamotrigine for intractable migraine-like headaches in Sturge–Weber syndrome

We herein report that naratriptan remarkably improved intractable migraine-like headaches in a patient with Sturge–Weber syndrome (SWS) despite his past history of cerebral infarction. In addition, lamotrigine had a prophylactic effect on his visual aura and headaches. An 18-year-old male patient with SWS had intractable migraine-like headaches every several months from the age of 3 years. His migraine-like headaches were characterized by pulsating attacks preceded by left homonymous hemianopsia, which persisted after headache disappearance. In addition, after 14 years of age, the pulsating headaches were preceded by photophobia without homonymous hemianopsia and occurred almost daily. Headache pains were not improved by acetaminophen or loxoprofen sodium hydrate. Furthermore, various prophylactic drugs were ineffective. After obtaining informed consent, naratriptan was administered. The pain severity was reduced and the duration of headache with homonymous hemianopsia was shortened from several days to several hours. Interestingly, naratriptan also shortened the duration of homonymous hemianopsia to several hours. We confirmed that his headache attacks were not epileptic seizures by ictal electroencephalography. However, 25 mg/day of lamotrigine had a prophylactic effect on the frequency of headache. Moreover, lamotrigine led to complete remission of his headache without homonymous hemianopsia. Lamotrigine may have an advantage in terms of reducing the risk of cerebrovascular disease caused by migraine-like headaches and the use of triptans. The most effective management for migraine-like headaches in patients with SWS has not been established. Lamotrigine is a potentially effective option for patients with SWS with migraine-like headaches.     

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。     

Sudden unexpected death in epilepsy in lamotrigine randomized‐controlled trials

Purpose: Nonrandomized studies of the relationship of antiepileptic drugs (AEDs) with sudden unexpected death in epilepsy (SUDEP) may be susceptible to confounding by tonic–clonic seizure frequency, polypharmacy, and other potential risk factors for SUDEP. We evaluated the risk of SUDEP with lamotrigine (LTG) compared to active comparators and placebo in randomized controlled clinical trials conducted by GlaxoSmithKline (GSK) between 1984 and 2009. Methods: Among 7,774 subjects in 42 randomized clinical trials, there were 39 all‐cause deaths. Ten deaths occurred >2 weeks after discontinuation of study medication and were excluded. Narrative summaries of deaths were independently reviewed by three clinical experts (TT, LH, DF), who were blinded to randomized treatment arm. The risk of definite or probable SUDEP was compared between treatment arms for each trial type (placebo‐controlled, active‐comparator, crossover), using exact statistical methods. Key Findings: Of 29 on‐treatment deaths, eight were definite/probable SUDEP, four were possible SUDEP, and 17 were non‐SUDEP. The overall, unadjusted rate of definite/probable SUDEP for LTG was 2.2 events per 1,000‐patient years (95% confidence interval [95% CI] 0.70–5.4). The odds ratios (OR) for on‐treatment, definite/probable SUDEP in LTG arms relative to comparator arms, adjusted for length of exposure and trial, were the following: placebo‐controlled, OR 0.22 (95% CI 0.00–3.14; p = 0.26); active‐comparator, OR 2.18 (95% CI 0.17–117; p = 0.89); and placebo‐controlled cross‐over, OR 1.08 (95% CI 0.00–42.2; p = 1.0). Significance: There was no statistically significant difference in rate of SUDEP between LTG and comparator groups. However, the CIs were wide and a clinically important effect cannot be excluded.