拉莫三嗪与丙戊酸钠治疗癫对比分析

传统抗癫药物(AEDS)可使70%左右的癫发作得到有效控制,但仍有30%的患者通过传统AEDS正规治疗,发作仍不能被有效控制。国外自上世纪90年代起,有不少利用一些新型AEDS治疗癫的报道[1-2],我院将新型抗癫药物拉莫三嗪(lamotrigine,LTG)用于治疗癫患者,现报道如下。1对象与方法1.1对象病例来自我院2011-01—2012-01我院就诊癫患者,入选标准:(1)年龄18～58岁;(2)按照国际抗癫联     

拉莫三嗪对双相抑郁的治疗与预防

对拉莫三嗪治疗双相抑郁障碍的有效性进行了综述。     

拉莫三嗪治疗双相抑郁的对照研究

目的 评价拉莫三嗪治疗双相抑郁的疗效和安全性.方法 将62例双相抑郁发作患者随机分为拉莫三嗪组31例,碳酸锂组31例.分别口服拉莫三嗪50～250 mg/d,碳酸锂500～2 000 mg/d,疗程8周,分别于治疗前及治疗后2、4、8周末采用17项汉密尔顿抑郁量表(HAMD)、临床总体印象-严重度量表(CGI-S)进行评定.结果 治疗8周末,两组均取得较好的显效率及有效率,且拉莫三嗪组优于碳酸锂组;两组CGI较治疗前显著减少(P＜0.05),而两组间无统计学意义(P＞0.05).两组HAMD评分与治疗前比较于治疗4周末始,均明显降低(P＜0.05);而且治疗8周末,拉莫三嗪组HAMD评分明显低于碳酸锂组(P＜0.05).拉莫三嗪组不良反应较碳酸锂组少而轻.结论 拉莫三嗪治疗双相抑郁有较好疗效,且安全性较好.     

拉莫三嗪与丙戊酸钠治疗癫痫的疗效及对TCTGHDL-C及LDL-C水平的影响

目的：观察拉莫三嗪（lamotrigine ,LTG）与丙戊酸钠（valproate ,VPA）对癫痫（epilepsy ,EP）患者 TC、TG、HDL-C及LDL-C水平的影响。方法2011-03-2012-03我院确诊86例EP患者,分为观察组（43例）及对照组（43例）。对照组以V PA药物治疗,观察组加用L T G。对比2组疗效及治疗前后患者血脂水平的变化情况。结果观察组控制率55.81％（24/43）,有效率13.95％（6/43）,总有效率97.67％（42/43）,均显著高于对照组的32.56％（14/43）、32.56％（14/43）及83.72％（36/43）;而无效率2.33％（1/43）,显著低于对照组的16.28％（7/43）,差异均有统计学意义（ P＜0.05）。观察组患者血脂水平主要表现为先上升后下降趋势,且TC、TG及LDL-C在治疗6、12个月后的水平均显著低于对照组,差异均有统计学意义（P＜0.05）。结论 VPA联合LTG治疗EP可明显提升疗效,同时血脂水平较为稳定,值得临床推荐。     

拉莫三嗪联合丙戊酸钠治疗脑卒中继发癫痫患者的疗效观察

目的 观察拉莫三嗪联合丙戊酸钠治疗脑卒中继发癫痫患者的临床疗效.方法 选取我院2011-01-2012-01收治的80例脑卒中继发癫痫患者为研究对象,将患者抽签速记分为观察组与对照组,每组40例.对照组给予丙戊酸钠治疗,观察组给予拉莫三嗪联合丙戊酸钠治疗,比较2组临床疗效,比较治疗前、治疗6个月、12个月后癫痫发作持续时间、生活质量评分及不良反应发生率.结果 观察组有效率95.00％,高于对照组的80.00％,差异有统计学意义(P＜0.05).2组治疗前癫痫发作持续时间、生活质量评分比较差异无统计学意义(P＞0.05);治疗6个月、12个月后癫痫发作持续时间(2.76±1.53)min/次、(2.25±1.23)min/次,低于对照组;生活质量评分(63.82±6.30)分、(78.95±6.71)分,高于对照组,差异均有统计学意义(P＜0.05).2组不良反应发生率比较差异无统计学意义(P＞0.05).结论 拉莫三嗪联合丙戊酸钠治疗脑卒中后继发性癫痫,可提高临床疗效,缩短癫痫发作持续时间,提高生活质量,且不增加不良反应发生率,具有较好的临床应用价值.     

拉莫三嗪治疗双相心境障碍对照研究

目的：探讨拉莫三嗪治疗双相情感障碍的疗效与安全性。方法：双相心境障碍患者135例,其中双相抑郁78例,躁狂57例。将患者随机分为3组,每组抑郁相26例,躁狂相19例。疗程32周。前8周为急性期治疗阶段,对照组抑郁相只服选择性5-羟色胺回收抑制剂（SSRI）类抗抑郁剂,躁狂相只服利培酮;拉莫三嗪组在对照组用药的基础上加服拉莫三嗪;碳酸锂组在对照组用药的基础上加服碳酸锂。后24周为巩固治疗阶段,所有患者随机分为两组,只服拉莫三嗪或碳酸锂。采用汉密尔顿抑郁量表（HAMD）、Young躁狂评定量表（YMRS）、治疗中出现的症状量表（TESS）评定疗效及安全性。结果：急性期治疗结束后,无论躁狂相还是抑郁相,拉莫三嗪组和碳酸锂组的临床疗效显著高于对照组（P〈0．01或〈0．05）。巩固治疗阶段两组相比,拉莫三嗪的抗抑郁作用较好,碳酸锂的抗躁狂作用较强。不良反应发生率,碳酸锂组40％,拉莫三嗪组22％。巩固治疗阶段病情复发率,拉莫三嗪组8％,碳酸锂组11％,两组差异无显著性（P〉0．05）。结论：拉莫三嗪作为心境稳定剂治疗双相情感障碍疗效可靠,不良反应小,与碳酸锂相比,抗抑郁作用更强。     

拉莫三嗪合并丙戊酸钠致Stevens Johnson综合征1例

<正>1病例患者男,67岁。因失眠、烦躁、情绪低落与兴奋话多交替发作1年余,加重1个月第2次住我院治疗。患者于2011年7月因人际关系处理不当,逐渐起病,表现内疚、自责、失眠,晚上入睡困难、早醒,醒后不能继续入睡。情绪低落,对任何事情均不感兴趣,认为活着没有意思。烦躁,有时坐立不安,出虚汗,浑身无力,曾因无力导致摔伤牙齿。急躁时感觉嗓子发哑、耳鸣,饮食差,至发病以来体质量下降近5 kg,怕冷。     

小剂量拉莫三嗪与丙戊酸合用治疗成人癫痫临床观察

目的 研究小剂量拉莫三嗪与丙戊酸合用治疗成年人各种类型癫痫的有效件和安全性.方法 对100例成年癫痫患者采用逐步增量的方法给予拉莫三嗪至每目100 mg,加约期4周,并继续服用原剂量的丙戊酸治疗,连续观察6月,记录患者发作的情况及不良反应.结果 小剂量拉其三嗪与丙戊酸合用总有效率为77.2%,完全控制50.O%,各种类型发作之间疗效比较差异无显著性(χ2=1.37,P>0.05);各型癫痫在人组4～6个月后较入组前3个月发作频率均减少,差异有显著性(P<0.05).不良反应发生率23.7%,与入组前后小良反应发牛率相比无显著变化(χ2=0.21,P>0.05).结论 小剂量托莫二三嗪与丙戊酸合用治疗成年人各种类犁癫痫均取得良好疗效,不良反应无增加.     

传统抗癫痫药丙戊酸添加拉莫三嗪治疗难治性癫痫

新诊断的癫痫患者主要使用抗癫痫药物(AED)治疗,其中大部分患者服用一种传统的AED后即不再发作,一部分患者需要联合多种AED(包括新型的AED)才能控制发作,能够利用AED很快得到控制的癫痫患者占70%左右.还有部分患者在接受了多种药物治疗后仍然不能控制病情,称为难治性癫痫.约占癫痫患者的30%,如何对这些患者进行有效的治疗,是目前癫痫诊治中的重要问题.本研究在传统抗癫痫药物丙戊酸治疗癫痫的基础上,添加拉莫三嗪治疗难治性癫痫,取得了较好的临床效果,报告道下.     

碳酸锂合并丙戊酸钠预防双相障碍复发的研究

目的比较碳酸锂合并丙戊酸钠与单用碳酸锂对预防双相障碍复发的疗效。方法对82例临床康复的双相障碍患者随机分为碳酸锂合并丙戊酸钠组及单用碳酸锂组,合并用药组44例,单用碳酸锂组38例,随访观察2年。结果合并用药组有效率为88.6%,单用碳酸锂组有效率为68.4%,两组比较差异有显著性(P<0.05)。结论碳酸锂合并丙戊酸钠对双相障碍有较好的预防复发作用。     

丙戊酸钠与无抽搐电休克治疗中老年双相情感障碍躁狂发作的疗效对比

目的对比丙戊酸钠注射液与无抽搐电休克治疗中老年双相情感障碍躁狂发作的疗效。方法选择我院收治的86例中老年双相情感障碍躁狂发作患者,采用随机数表法将86例患者分为对照组43例和观察组43例,2组均予以常规药物治疗,对照组在常规治疗基础上进行无抽搐电休克治疗,观察组予以丙戊酸钠注射液治疗,治疗2周后使用杨式躁狂评定量表(YMRS)评价症状改善情况,使用连线(TMT)测验与威斯康星卡片分类(WCTS)测验比较2组认知功能改善情况,对比2组预后情况。结果治疗后2组YMRS评分与治疗前相比均降低,治疗后1周2组YMRS评分无明显差异(P0.05);治疗后2周观察组YMRS评分显著低于对照组(P0.05);治疗2周后观察组TMT与WCTS结果均优于对照组(P0.05);观察组住院时间、住院费用、复发次数、约束时间和约束次数均低于对照组(P0.05)。结论在中老年双相情感障碍躁狂发作的治疗中应用丙戊酸钠注射液的效果优于无抽搐电休克治疗,可更好改善患者的症状,缩短住院时间,节省治疗费用,值得临床推广。     

托吡酯联合舍曲林治疗双相抑郁急性发作的对照研究

目的 评价与拉莫三嗪联合舍曲林治疗双相抑郁急性发作相比,托吡酯联合舍曲林治疗双相抑郁的疗效及安全性.方法 将符合CCMD -3双相抑郁诊断标准的68例患者随机进入拉莫三嗪联合舍曲林组(研究组)或托吡酯联合舍曲林组(对照组)接受治疗,最终研究组有30例和对照组有34例完成治疗,分别在治疗前和1、2、4、6、8周末评定HAMD、HAMA、TESS总分.结果 两组间HAMD、HAMA评分在第4、6周末具有统计学意义(P＜0.01,P＜0.05).两组内各阶段末HAMD、HAMA评分具有统计学意义(P＜0.01),提示托吡酯联合组与拉莫三嗪联合组对双相抑郁急性发作有效.两组TESS不良反应在第2、4周末差异具有统计学意义(P＜0.01).结论 托吡酯联合舍曲林治疗双相抑郁在疗效方面,有效且起效时间快;在安全性方面,托吡酯联合舍曲林治疗双相抑郁时不良反应较早出现,但经过持续坚持观察治疗后,在不良反应方面与拉莫三嗪联合舍曲林治疗双相抑郁的不良反应相当.     

Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy

PURPOSE: Treatment with sodium valproate (VPA) may be associated with polycystic ovarian syndrome (PCOS) in some women with epilepsy. By comparing hormone profiles in young adults taking VPA or lamotrigine (LTG) as monotherapy, this study aimed to explore whether a pharmacologic effect of VPA could be responsible for this observation. METHODS: Hormone profiles in men and women taking VPA (n = 40) or LTG (n = 36) monotherapy for epilepsy were compared. None of the women were receiving hormonal contraception or replacement. Patients gave details of seizure type and frequency, menstrual cycle, and medical and drug history. Body mass index was calculated, and fasting insulin, glucose, cholesterol, triglycerides (TG), high- and low-density lipoproteins, testosterone, dihydroepiandosterone (DHEA), androstenedione, sex hormone-binding globulin (SHBG), free androgen index (FAI), luteinising hormone (LH), follicle-stimulating hormone (FSH), and antiepileptic drug (AED) concentrations were measured. RESULTS: There were no differences between treatment groups for both sexes in age and seizure control. Only four obese VPA-treated women were hyperinsulinaemic (p = 0.05); three with abnormal menstrual cycles; one with raised testosterone. Testosterone (p = 0.02), FAI (p = 0.03), and TG (p = 0.02) levels were higher, however, in women taking the drug. Obese patients of both sexes (p = 0.01) and VPA-treated men (p = 0.03) had higher insulin concentrations. CONCLUSIONS: VPA therapy may be associated with subclinical elevation in fasting insulin levels. Testosterone and TG levels were higher in VPA-treated women compared with the levels in those taking LTG. However, only a minority of obese females exhibited biochemical characteristics suggestive of PCOS. Biochemical screening may allow women at risk of developing PCOS to avoid VPA.     

拉莫三嗪治疗精神分裂症和双相抑郁及重性抑郁症耐受性与敏感性的文献分析

目的 分析拉莫三嗪在精神分裂症、双相抑郁和重性抑郁症急性期治疗中耐受性与敏感性.方法 选择符合急性期、随机双盲、安慰剂对照的关于拉莫三嗪治疗急性期精神分裂症、双相抑郁和重性抑郁症的临床试验进行分析;以不良事件引起治疗终止发生率为拉莫三嗪的耐受性指标,以皮疹和头痛为敏感性指标.分别计算拉莫三嗪(200 mg/d)事件发生率相对于安慰剂事件发生率增加(ARI),以及拉莫三嗪(200 mg/d)治疗相对于安慰剂治疗所致1例不良事件发生前需要治疗的患者数(NNH);显著性检验以95%可信区间(95%CI)表示.结果 (1)难治性精神分裂症4项、双相抑郁4项、难治性双相抑郁1项和重性抑郁症3项临床试验被分析;(2)在难治性精神分裂症、双相抑郁及难治性双相抑郁、重性抑郁症的急性治疗期,与安慰剂比较,拉莫三嗪(200 mg/d)相关不良事件引起治疗终止NNH(95%CI)依次为323(-23～20)、-47(-17～60)、-34(-10～22)和-32(-14～158)例,皮疹依次为133(-51～29)、-46(-18～83)、51(-16～10)和-31(-15～1208)例,头痛依次为-26(-11～61)、-168(-16～19)、-28(-6～9)和53(-24～13)例,差异无统计学意义(95%CI包括0).结论 拉莫三嗪单药或增效治疗精神分裂症、双相抑郁和重性抑郁症具有良好的耐受性与安全性.

Abstract：

Objective To compare the tolerability and sensitivity of lamotrigine in the treatment of schizophrenia, bipolar depression and major depressive disorder (MDD). Methods Data from randomized,double-blind, placebo-controlled trials of lamotrigine adjunctive or monotherapy in the acute treatment of treatment-resistant schizophrenia, bipolar depression, and MDD were used. The discontinuation due to adverse events (DAEs) was used as an index of tolerability. The reported headache and occurrence of rash were used as indexes of sensitivity. Absolute risk increase (ARI) and number needed to harm (NNH) of lamotrigine at dose of 200 mg/d relative to placebo for DAEs, headache, and rash were estimated with 95% confidence interval (CI) to reflect the magnitude of variance. Results Four trials in treatment-resistant schizophrenia, 4 in bipolar depression, 1 in treatment-resistant bipolar depression and 3 in major depressive disorder were analyzed. In the acute treatment of treatment-resistant schizophrenia, bipolar depression or treatment-resistant bipolar depression and major depressive disorder, lamotrigine 200 mg/d did not significantly increase the risk for DAEs [NNH 95% CI respectively as 323(-23 to 20) ,-47(-17 to 60), -34(-10 to 22) and-32(-14 to 158)], rash [NNH 95% CI respectively as 133 (-51 to 29),-46(-18 to 83), 51 (-16 to 10) and -31 (-15 to 1208)] and headache [NNH 95% CI respectively as -26(-11 to 61),-168 (-16 to 19),-28 (-6 to 9) and 53 (-24 to 13)] relative to placebo. Conclusion The available data indicate patients with schizophrenia, bipolar depression and major depressive disorder tolerate lamotrigine 200 mg/d as well as placebo and have a similar sensitivity to lamotrigine as to placebo.     

拉莫三嗪维持治疗双相障碍躁狂发作的疗效评价

目的评价拉莫三嗪维持治疗双相障碍躁狂发作的疗效。方法将73例维持期双相障碍躁狂发作患者随机分为两组，研究组用拉莫三嗪系统治疗，对照组用碳酸锂系统治疗，共治疗12周，并在入组时和治疗后第4、12、24周末评定蹂狂量表（BRMS）和社会功能缺陷筛查量表（SDSS），分别评估躁狂症状严重程度和社会功能受损情况，副反应量表（TESS）评定不良反应。结果在治疗第4周末及第12周末，研究组BRMS和SDSS评分均较治疗前有显著性降低（P〈0.05），而对照组无显著性变化。治疗第4周末、第12周末及第24周末，研究组的BRMS和SDSS评分均显著低于对照组（P〈0.05）。结论拉莫三嗪对双相障碍躁狂发作的维持期治疗有显著疗效，且可有效改善患者的社会功能。     

丙戊酸钠与碳酸锂治疗躁狂发作对照研究

目的：比较丙戊酸钠与碳酸锂治疗躁狂发作的疗效和不良反应。方法：对80例躁狂发作患者随机均分为丙戊酸钠组和碳酸锂组，在治疗前，治疗2、4、8周末分别用Bech-Rafaelsen躁狂量表(RBRMS)和临床疗效总评量表(CGI)及副反应量表(TESS)评定疗效和不良反应。结果：丙戊酸钠组治疗2周后BRMS总分，及各因子分比治疗前明显降低，且显著低于碳酸锂组，两组治疗8周BRMS总分各因子分均显著低于治疗前，差异显著。治疗2、4、8周末TESS评分，丙戊酸钠组显著低于碳酸锂组，差异有显著性。结论：丙戊酸钠治疗躁狂发作疗效好，起效快，不良反应小。     

Lurasidone adjunctive with lithium or valproate for bipolar depression: A placebo-controlled trial utilizing prospective and retrospective enrolment cohorts

In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium or valproate, patients with bipolar I depression were randomized to 6 weeks of double-blind treatment with lurasidone (N = 180) or placebo (N = 176), added to background treatment with lithium or valproate. All patients were treated with lithium or valproate for a minimum of 4 weeks prior to screening. This was confirmed either by prospective treatment after study enrolment (run-in cohort), or retrospectively, with blood levels of lithium and valproate at screening (non-run-in cohort). Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP-S), respectively. Treatment with lurasidone was associated with non-significant improvement at week 6 vs. placebo for the MADRS total score (−11.8 vs −10.4; P = 0.176), and the CGI-BP-S score (−1.36 vs −1.13; P = 0.095). Significant separation from placebo was observed from weeks 2–5 for the MADRS and weeks 3–5 for the CGI-BP-S. Improvement in the placebo-subtracted MADRS total score was notably larger at week 6 for the non-run-in cohort compared to the run-in cohort (LS mean difference in endpoint change scores, −4.6; P = 0.009). Adverse events most frequently reported for lurasidone were akathisia, somnolence, and extrapyramidal side effects. In conclusion, lurasidone adjunctive with lithium or valproate demonstrated significant improvement in depressive symptoms based on the MADRS from weeks 2–5 but not at the primary week 6 endpoint.     

Effectiveness of lamotrigine in bipolar disorder in a clinical setting

Objective

To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Method

Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results

One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean ± SD age 42.2 ± 14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1 ± 1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434 ± 444 days, and mean final dose was 236 ± 132 mg/day without valproate, and 169 ± 137 mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255 ± 242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264 ± 375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674 ± 479 days, but had subsequent psychotropic added at 146 ± 150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.

Conclusion

In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.