Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia - Efficacy and dose-response trials
Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia - Efficacy and dose-response trials
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DOI：
10.1097/00000542-200205000-00005
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发表时间：
2002-05-01
期刊：
影响因子：
8.8
通讯作者：
Max, MB
中科院分区：
文献类型：
--
作者：
Sang, CN;Booher, S;Max, MB
背景：N-甲基-D-天冬氨酸谷氨酸受体拮抗剂在神经病理性疼痛患者中的重复剂量对照试验很少。作者试图使用一种新的两阶段设计来评估两种低亲和力N-甲基-D-天冬氨酸拮抗剂。作者在两项交叉试验中研究了疼痛性糖尿病神经病变（DN）和带状疱疹后神经痛（PHN）患者：（1）疗效试验（美沙芬vs美金刚）。活性安慰剂[劳拉西泮]）和（2）在来自第一项研究的应答者中优选活性药物的剂量反应试验（每名患者的最大耐受剂量的0%对25%对50%对100%）。结果：23例DN患者中有19例和21例PHN患者中有17例完成了疗效试验。DN和PHN的中位剂量分别为400和400 mg/天甲氨蝶呤，55和35 mg/天美金刚，1.8和1.2 mg/天劳拉西泮。在疗效试验中，在DN患者中，美沙芬使疼痛强度较基线平均降低33%，美金刚使疼痛强度平均降低17%，劳拉西泮使疼痛强度平均降低16%;达到中度以上疼痛缓解的受试者比例为美沙芬68%，美金刚47%，劳拉西泮37%。PHN患者的疼痛强度平均降低6%，美沙芬，美金刚胺2%，劳拉西泮0%。在疗效试验中，与安慰剂的比较未达到统计学显著性。在10例DN患者中，右美沙芬对疼痛强度有显著的剂量反应效应（P = 0.035），最高剂量明显优于劳拉西泮（P = 0.03）。结论：右美沙芬对DN患者的治疗效果与剂量有关。PUN的情况并非如此，这表明疼痛机制存在差异。选择性方法疼痛相关的N-甲基-D-天冬氨酸受体是必要的。
Background: There are few repeated dose-controlled trials of N-methyl-D-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-D-aspartate antagonists using a novel two-stage design.Methods. The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine rs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale.Results: Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorplian, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain Intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03).Conclusions: Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PUN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-D-aspartate receptors are warranted.