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Clinical Efficacy of New Antiepileptic Drugs in Refractory Partial Epilepsy: Experience in the United States With Three Novel Drugs 总被引:1,自引:1,他引:0
Jacqueline A. French 《Epilepsia》1996,37(S2):S23-S26
Summary: A number of new antiepileptic drugs (AEDs), including topiramate (TPM), felbamate (FBM), and gabapentin (GBP), are approved or believed to be close to approval for marketing in the United States. Key efficacy findings for these AEDs in refractory partial epilepsy were reviewed. Large and significant drug-placebo differences were observed with TPM in two large dose-finding trials conducted in the United States. The minimal effective dose of TPM in the population studied was determined to be approximately 200 mg/day, and doses above 600 mg/day produced good efficacy but little incremental benefit versus the lower dosages for the overall study population. FBM is active in partial epilepsy, although seizure reduction is less marked and drug interactions complicate the findings. GBP is also active in this population, but only the 1,800 mg/day dosage was significantly better than placebo with respect to percent re-sponders. It may be useful to explore higher dosage ranges for both FBM and GBP if they can be well tolerated. 相似文献
3.
目的研究托吡酯(TPM)对慢性癫痫大鼠海马碱性成纤维细胞生长因子(bFGF)表达的影响。方法制作戊四氮(PTZ)慢性癫痫点燃大鼠模型,分为PTZ组、TPM组及正常对照组,每组又以5d、10d、15d3个时间点各分为3小组。免疫组化法观察各组海马CAl、CA3区及齿状回bFGF表达,HE染色观察病理形态学改变。结果(1)行为学观察:PTZ组和TPM组在癫痫发作上无明显差别。(2)bFGF表达:①各组齿状回区bFGF表达:PTZ组和TPM组各时点表达不断增高,与正常对照组比较差异有统计学意义(均P〈0.01),尤以10d及15d时增高更明显,与5d时比较差异有统计学意义(均P〈0.05)。②各组CAl区bFGF表达:PTZ组各时点均有明显表达,且随时间延长而表达不断增高,各时点比较差异有统计学意义(均P〈0.01),与正常对照组比较差异有统计学意义(均P〈0.01);TPM组在5d时与正常对照组比较差异有统计学意义(P〈0.01),而10d、15d时逐渐下降,接近正常对照组水平。③各组CA3区bFGF表达:5d时3组比较差异无统计学意义。但PTZ组和TPM组在10d时与正常对照组比较差异有统计学意义(P〈0.01),PTZ组在15d时和TPM组及正常对照组比较差异有统计学意义(均P〈0.01)。(3)病理形态学改变:PTZ组和TPM组的海马CAl、CA3区尤其是CAl区可见较多神经元发生变性和坏死,PTZ组更显著。结论PTZ点燃过程中海马bF-GF表达增高,尤其在CAl区,且随时间延长有表达不断增高的趋势。TPM可能通过减少海马神经元损伤而明显下调海马CAl、CA3区bFGF的表达。 相似文献
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The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice 总被引:1,自引:0,他引:1
Hans-Peter R. Bootsma †Albert P. Aldenkamp Leonie Diepman Jacques Hulsman Danielle Lambrechts Loes Leenen Marian Majoie Ad Schellekens †Marc de Krom 《Epilepsia》2006,47(S2):24-27
Summary: Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV. 相似文献
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV. 相似文献
6.
In this review the state of the art of treating patients with epilepsy in the nineties in the Netherlands is presented. It describes general strategies for treatment with antiepileptic drugs and the history of development of the classical anticonvulsant drugs. Eight new drugs, including vigabatrin, lamotrigine, felbamate, oxcarbazepine, gabapentin, tiagabine, levetiracetam and topiramate are discussed. A review of their pharmacological and clinical properties is presented. Dutch experience with these drugs is included. 相似文献
7.
目的:观察托吡酯预防动物热性惊厥发作的疗效与毒副反应。方法:60只对热惊厥敏感的Wistar大鼠,随机分为两组,分别按4或8mg/(k·d)的剂量灌服托吡酯20d后,观察其热性惊厥敏感性改变情况和毒副反应。结果:Wistar大鼠用药后,在热水浴中发生惊厥的时间分别从(247.8±84.9)s、(243.4±99.4)s延长到(353.6±79.3)s、(329.2±78.1)s(t分别为3.07、3.59,P均<0.01);发生惊厥的持续时间分别从(283.0±112.3)s、(298.3±84.0)s缩短到(178.9±84.8)s、(230.3±74.0)s(t分别为3.33、4.18,P均<0.01);热惊厥发生程度也明显减轻,分别从2.9±0.9、2.7±0.7降低到1.8±0.9、1.3±0.9(t分别为4.89、6.65,P均<0.01);热惊厥控制率达95%(57/60,P<0.01);不良反应发生率虽然较高为65.0%(39/60),但表现轻微,而引起动物死亡等严重不良反应发生却只有16.7%(10/60),两者相比差异非常显著(χ2=29.1,P<0.01),而血常规和肝肾功均无异常改变。结论:托吡酯用于预防动物热性惊厥的发生具有剂量较小,疗效高,安全性较好等优点。 相似文献
8.
托吡酯治疗儿童癫癎出现泌汗障碍的临床观察与随访 总被引:4,自引:0,他引:4
目的研究托吡酯治疗儿童癫癎时出现的泌汗障碍(少汗或无汗)及其对策.方法通过追踪随访了解泌汗障碍与托吡酯服用的时间、季节、剂量、加药速度等的关系,合用其他抗癫癎药的影响,以及出现泌汗障碍后的转归.结果泌汗障碍与托吡酯服用的时间、剂量、加药速度无相关性,不同患儿间存在很大差异,不受合并用药的影响,高温时节症状明显,减缓加药速度可增加易感患儿对泌汗障碍的耐受性.结论托吡酯治疗儿童癫癎时出现的泌汗障碍为托吡酯所致,停药后泌汗功能恢复正常,大部分患儿对其耐受性好,泌汗障碍为非器质性损伤. 相似文献
9.
Bahram Mohammadi Klaus Krampfl Cener Cetinkaya Heiner Wolfes Reinhard Dengler Johannes Bufler 《Pharmacological research》2005,51(6):587-592
Glycine receptor channels are pentameric ligand-gated ion channels that respond to the application of inhibitory neurotransmitters by opening of a chloride-selective central pore. Topiramate (TPM) is a broad-spectrum antiepileptic drug used as add-on or monotherapy for focal seizures. In the present study the interaction of TPM with glycine receptor channels was studied on outside-out patches from HEK293 cells expressing alpha1beta glycine receptor channels. The patch clamp techniques combined with ultra fast solution exchange enabled us to investigate the kinetics of receptor channels in presence of TPM. Our study showed no agonistic or potentiating effect for TPM on glycine receptor channels. However, in presence of 1 mM glycine + 1 mM TPM, the desensitization got faster and the peak current amplitude decreased. After the end of glycine + TPM pulses, off-currents occurred, suggestive for a specific channel block mechanism. 相似文献
10.
PURPOSE: There is controversy between clinicians and statisticians on the appropriateness of the number needed to treat (NNT) as a summary statistic to report the effectiveness of a treatment. We examine the two viewpoints and make proposals concerning the reporting of clinical trial results. METHODS: In the context of antiepileptic treatments, we explain the two different viewpoints and illustrate the use of the odds ratio, relative risk, absolute difference, and NNT on the results of randomized clinical trials with topiramate (TPM). Special attention is paid to the use of these summary statistics in meta-analyses. Here, the NNT is the expected number of patients one would need to treat to achieve a single occurrence of a specified good outcome (e.g., 50% reduction in seizure rate) in comparison to no (or placebo) treatment. RESULTS: Although the NNT is readily interpretable in some instances, it exhibits undesirable statistical behavior in other cases. In particular, confidence intervals for the NNT may split into two intervals and extend to positive and negative infinity when treatment efficacy is not clearly established by the data. Meta-analyses cannot be sensibly conducted directly on the NNT scale. CONCLUSIONS: Although other measures, such as the odds ratio, have been more commonly used in the context of meta-analyses, clinicians prefer the NNT because it gives them a clearer clinical interpretation of the effectiveness of a (new) treatment. On the other hand, statisticians do not recognize the value of the NNT, as it has undesirable statistical properties. Some reconciliation between the two views could be achieved when the clinicians acknowledge the weak aspects of the NNT and when statisticians realize that statistical appropriateness is not the same as clinical relevance. It is suggested that the NNT be used as a secondary reporting tool not on an equal footing with the classic scales. 相似文献