Lamotrigine-antiparkinsonian activity by blockade of glutamate release?

Summary Recent experiments provide evidence that the NMDA-antagonist MK-801 has a locomotor-stimulating effect in monoamine-depleted rodents. These findings are based upon a hypothetical pathway-circuit including the basal ganglia as a model reflecting hypo- and hyperkinetic movement disorders. We have treated 5 patients suffering from Parkinson's disease with the antiepileptic drug lamotrigine which does not appear to be an NMDA-antagonist but acts functionally as a glutamate antagonist by inhibition of presynaptic glutamate release.     

Treatment-refractory bipolar disorder: classification to aid in clinical management

Bipolar disorder is an illness with complex symptomatology that encompasses severe symptoms of mood and thought disorder and can limit the cognitive range of human brain functioning. The Diagnostic and Statistical Manual, 4th edition and International Classification of Mental Disorder recommend subgroups of bipolar disorder based on symptoms, illness severity, and frequency of episodes. Pharmacological agents commonly used in the management of bipolar disorder include lithium; anticonvulsants, such as valproate, carbamazepine and lamotrigine; and recent years have witnessed increasing use of atypical antipsychotics. There are several intra- and inter-class differences in these compounds, especially relating to polarity of mood episode under consideration. Monotherapy trials have focused on efficacy of the compounds; few have explored combination therapy, especially in patients failing to respond or inadequately responding to one agent. Clinicians have frequently prescribed two or more compounds to stabilize moods. Monotherapy treatment of bipolar manic episode with various compounds including atypical antipsychotics, mood stabilizers such as lithium, valproic acid and carbamazepine yielded response rates of 50%. However, combination therapy of atypical antipsychotics with valproic acid or lithium offered an additional 20% improvement in the response rates. The article will review published data on augmentation studies, comment on case reports published in treatment-refractory bipolar disorder, and propose a new classification guideline for staging treatment-refractory bipolar disorder.     

高效液相色谱法测定人血浆中拉莫三嗪的浓度

目的建立测定人血浆中拉莫三嗪浓度的高效液相色谱法。方法色谱柱为SunFire C18(4.6 mm×250mm,5μm),流动相为水-乙腈-三乙胺(64.5:35:0.5,v/v/v),磷酸调节pH至6.5,流速为1.0 mL·min-1,血浆标本经乙酸乙酯-二氯甲烷(75:25,v/v)提取后,在237 nm波长下进行检测。结果拉莫三嗪在0.312 5⁴0.0μg·mL-1与峰面积呈良好的线性关系(Y=0.047 2X+0.069 3,r2=0.999 2),相对回收率均在82%40.0μg·mL-1与峰面积呈良好的线性关系(Y=0.047 2X+0.069 3,r2=0.999 2),相对回收率均在82%¹05%,日内和日间RSD均<5%。结论该方法专属性强、准确度好、灵敏度高、操作简便,适合临床上对拉莫三嗪血药浓度的常规监测。     

Review of lamotrigine and its clinical applications in epilepsy

Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.     

不同剂量拉莫三嗪治疗老年癫痫的比较研究

目的 探讨不同剂量拉莫三嗪治疗老年癫痫患者的临床疗效。方法 选择2014年7月—2018年2月洛阳市第三人民医院神经内科诊治的老年癫痫患者88例作为研究对象,根据拉莫三嗪使用剂量分为对照组（40例）和观察组（48例）。对照组患者给予大剂量拉莫三嗪片治疗,拉莫三嗪起始剂量25 mg/d,2周后为50 mg/d,第5周以后为目标剂量100 mg/d,维持100 mg/d治疗观察至第8周。观察组患者给予小剂量拉莫三嗪片治疗,起始剂量25 mg/d,2周后为50 mg/d,第5周以后为目标剂量50 mg/d,维持50 mg/d治疗观察至第8周。观察两组患者的临床疗效,同时比较两组患者蒙特利尔认知评估量表（MoCA）评分、P300潜伏期、波幅和不良反应情况。结果 治疗后,对照组和观察组总有效率分别为97.5%、97.9%,两组对比差异无统计学意义。治疗后,两组患者的MoCA评分均显著高于治疗前,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组治疗后的MoCA评分显著高于对照组,两组比较差异具有统计学意义（P<0.05）。治疗后,观察组的P300潜伏期显著降低,波幅明显升高,同组治疗前后比较差异具有统计学意义（P<0.05）;且观察组治疗后P300潜伏期及波幅显著优于对照组,两组比较差异具有统计学意义（P<0.05）。观察组治疗期间的不良反应发生率为6.3%,显著低于对照组的32.5%,两组比较差异具有统计学意义（P<0.05）。结论 相对于大剂量,小剂量拉莫三嗪治疗老年癫痫患者能达到很好的疗效,能减少不良反应的发生,改善患者的神经电生理功能与认知功能。     

Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review

Sienaert P, Lambrichts L, Dols A, De Fruyt J.
Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review.
Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment‐resistant bipolar depression, as found in randomized controlled trials and with special attention to the definition and assessment of treatment resistance. Methods: A Medline search (from database inception to May 2012) was performed using the search terms treatment resistance or treatment refractory, and bipolar depression or bipolar disorder, supplemented with 43 separate searches using the various pharmacologic agents or technical interventions as search terms. Results: Only seven studies met our inclusion criteria. These studies examined the effects of ketamine (n = 1), (ar)modafinil (n = 2), pramipexole (n = 1), lamotrigine (n = 1), inositol (n = 1), risperidone (n = 1), and electroconvulsive therapy (ECT) (n = 2). Conclusions: The available level I evidence for treatment strategies in resistant bipolar depression is extremely scarce, and although the response rates reported are reassuring, most of the strategies remain experimental. There is an urgent need for further study in homogeneous patient samples using a clear concept of treatment resistance.     

拉莫三嗪对海人酸致癫大鼠血清S100β含量的影响

目的：建立海人酸致痫模型,用ELISA法检测致痫大鼠血清S100β含量的变化及拉莫三嗪对其含量的影响。方法：将72只28d龄的Wistar大鼠随机分为3组,生理盐水组24只,KA组24只,LTG组24只,KA组及LTG组大鼠分别在脑立体定位仪下于海马CA3区注射海人酸建立KA模型。LTG组在建立模型前12h进行LTG灌胃治疗2次,各组模型点燃成功后分别于6h、12h、24h、72h于右心室采血,ELISA法测定血清S100β含量值。结果：与生理盐水组比较KA组及LTG组血清S100β含量明显升高（P〈0.05）,但LTG组与KA组比较血清S100β含量无显著变化（P〉0.05）。结论：提示S100β与癫痫发作存在着密切的关系,LTG可能并不是通过降低致痫大鼠血清S100β含量而发挥抗癫痫作用。