October 1, 2009 — 研究者寻找难治型神经痛的新治疗方法，认为併gabapentinnortriptyline有效。他们提议将一个抗忧鬱药物加上解痉挛剂用於治疗难治型的神经痛。研究发现线上登载於9月30日的The Lancet期刊。
　　
第一作者、加拿大安大略皇后大学Ian Gilron医师在访问中向Medscape Neurology表示，神经疼痛相当具有挑战性，经常需使用多种药物。但是许多併用方式没有效果，我们希望在合理且有证据基础下研究併用方式。
　　
本试验由加拿大健康研究中心发起且提供支持。Gabapentin(加巴喷丁 )(商品名Neurontin，辉瑞药厂)是γ-胺基丁酸的一种3-烷基化相似物。原本发展用於治疗癲癇，但是已经普遍用於缓解疼痛。
　　
Nortriptyline去甲替林 (商品名Pamelor，诺华药厂)是amitriptyline的代谢物，据报告可以阻断正肾上腺素、血清素再吸收、钠通道、以及N-甲基-D-天(门)冬氨酸麩胺酸盐受体。
　　
丹麦Aarhus大学医院的Troels Jensen医师与Nanna Brix Finnerup医师在评论中表示，本研究颇受欢迎，因为我们极需改善此类慢性疼痛病患的治疗。
　　
神经疼痛影响了大约3%的人口，统合分析显示，获得适当疼痛缓解的病患不到三分之二(Pain 2005；118:289–305)。
　　
在最近的美国疼痛医学院年会中，专家进行有关难治型疼痛之挑战性的讨论。会议主持人、盐湖城犹他大学医学院的Perry Fine医师强调，目前的治疗可以完成的有限。

【治疗神经痛的挑战】
Jensen医师与Finnerup医师在文章中指出，一般而言，现有的药物缺乏分子特定性，而只作为抗痛觉敏感。现在已经在发展针对体觉皮质区特定部份的药物，可以在发生神经可塑型变化之前及早治疗。
　　
不过，一旦已经发生慢性疼痛，因其相关的生物、生理与社会影响，Jensen医师与Finnerup医师认为，单靠一、两种针对特定机转的药物仍可能无法治癒病患。
　　
在这个双盲、双虚拟交叉研究中，研究对象有56名病患；研究对象有糖尿病型多发性神经病变或者带状疱疹后神经痛，每日疼痛分数在0-10分的量表中至少4分。
　　
研究者随机将病患以1:1:1的比率进行分派。研究对象分别接受每天口gabapentinnortriptyline或併用两种。在治疗期间，研究者每6週调整药物，以达最大耐受剂量。
　　
试验的主要结果是在最大耐受剂量时的平均每日疼痛分数，採取治疗意向分析。
　　
Gilron医师等人发现，併用治疗组的疼痛显著低於单用gabapentin (-0.9；95%信心区间[CI]为 -1.4 至 -0.3; P = .001)或nortriptyline (-0.6；95% CI，-1.1至-0.1；P = .02) 。
　　
【最大耐受剂量的疼痛】治疗

治療	平均每日疼痛分數	95% CI
Gabapentin	3.2	2.5 – 3.8
Nortriptyline	2.9	2.4 – 3.4
併用	2.3	1.8 – 2.8

研究者报告指出，试验中没有任何病患有严重副作用；最常见的一般副作用为口乾，gabapentin组的病患体重增加较多。
　　
Gilron医师表示，併用治疗减少疼痛、也减少睡眠干扰且没有增加副作用。他也承认，这些效果还需要由其他中心研究验证。
　　
　Jensen医师与Finnerup医师指出，Gilron医师等人的试验结果来自研究者发起的两种神经痛常用药物的初步研究。可惜的是，这类研究很少见，因为多数药物研究是接受药厂资助、许多机构参与，以及大样本的研究。
　　
　现在这个研究的缺点是，研究者经费有限而限制了研究对象人数；他们使用交叉研究设计，每个病患也是自己的对照组。
　　
　研究者也没有提供比较相继使用与同时使用的效果的资料。Jensen医师与Finnerup医师指出，在临床实务，相继使用比较常见，但是在Gilron医师等人的研究中，同时给予了併用药物。
　　
　加拿大健康研究中心支持该研究。第一作者、Ian Gilron医师与资深作者、Robyn Houlden医师皆宣告接受辉瑞药厂的财务支持。编辑Troels Jensen医师宣告接受辉瑞、Eli Lilly以及Grunenthal等的资助。编辑Nanna Brix Finnerup医师宣告接受UCB Nordic的研究支持。
　　
　Lancet. 线上发表於2009年9月30日。

Combination Gabapentin and Nortriptyline May Ease Neuropathic Pain October 1, 2009 — Researchers looking for new ways to treat refractory neuropathic pain suggest that combining gabapentin with nortriptyline may be beneficial. They propose that adding an antidepressant to an anticonvulsant used for pain relief may ease difficult-to-treat neuropathic pain. Exploratory findings were published online September 30 in the Lancet. "Given the challenges of neuropathic pain, polypharmacy is frequently used," lead investigator Ian Gilron, MD, from Queen's University in Kingston, Ontario, Canada, said during an interview. "But many combinations are not beneficial. We wanted to study this combination in a rational and evidence-based way," Dr. Gilron told Medscape Neurology. Dr. Ian Gilron  The trial was investigator initiated and was supported by the Canadian Institutes of Health Research. Gabapentin (Neurontin, Pfizer) is a 3-alkylated analogue of γ aminobutyric acid. It was originally developed for the treatment of epilepsy but is widely used as a pain reliever. Nortriptyline (Pamelor, Novartis) is a metabolite of amitriptyline and reportedly blocks norepinephrine, serotonin uptake, sodium channels, and N-methyl-D-aspartate glutamate receptors. "This study is most welcome because improved treatment for patients with chronic types of pain is urgently needed," Dr. Troels Jensen and Dr. Nanna Brix Finnerup, from the Aarhus University Hospital in Denmark, said in an accompanying comment. Neuropathic pain affects an estimated 3% of the general population, and a meta-analysis showed that less than two thirds of patients obtain sufficient pain relief (Pain 2005;118:289–305). At the recent American Academy of Pain Medicine annual meeting, experts discussed the challenges of refractory neuropathic pain. Session moderator Perry Fine, MD, from the University of Utah School of Medicine, Salt Lake City, emphasized the limits to what can be accomplished with current therapies. Challenge of Treating Neuropathic Pain "Generally, available drugs lack molecular specificity and simply act as antihyperalgesics," Dr. Jensen and Dr. Finnerup add in their article. Drugs that target specific parts of somatosensory processing are now in development and could be used for early treatment before neuroplastic changes have taken place. However, once chronic pain has set in, with all of its associated biological, psychological, and social effects, Dr. Jensen and Dr. Finnerup suggest that 1 or even 2 drugs that target a specific mechanism are unlikely to cure the patient. In this double-blind, double-dummy, crossover trial, investigators studied 56 patients. Participants had diabetic polyneuropathy or postherpetic neuralgia and a daily pain score of at least 4 on a scale of zero to 10. Investigators randomly assigned patients in a 1:1:1 ratio. Participants received 1 of 3 sequences of daily oral gabapentin, nortriptyline, and a combination of both. During each 6-week treatment period, investigators titrated the drugs toward the maximum tolerated dose. The primary outcome for the trial was mean daily pain at maximum tolerated dose. Analysis was by intention to treat. Dr. Gilron and his team found that pain with combination therapy was significantly lower than with gabapentin (?0.9; 95% confidence interval [CI], ?1.4 to ?0.3; P = .001) or nortriptyline (?0.6; 95% CI, ?1.1 to ?0.1; P = .02) alone. Pain at Maximum Tolerated Dose Therapy  Mean Daily Pain  95% CI  Gabapentin 3.2 2.5 – 3.8 Nortriptyline 2.9 2.4 – 3.4 Combination 2.3 1.8 – 2.8 Investigators report no serious adverse events for any patients during the trial. The most common adverse effect was dry mouth, and the participants reported more weight gain in the gabapentin group. "Combination therapy decreased pain, but it also decreased sleep interference without increasing side effects," Dr. Gilron said. He acknowledged that these promising results will need to be replicated at other centers. "Gilron and colleagues' trial benefits from being an investigator-initiated study of 2 commonly used drugs for neuropathic pain," note Dr. Jensen and Dr. Finnerup. "This type of study is unfortunately rare because most drug studies are based on large sample sizes from many sites and financed by drug companies." A drawback of the current study was that the investigators had to keep costs down and thus limited the number of participants. They used a crossover design in which each participant served as his or her own control. The investigators also provide no data on the benefits of sequential vs simultaneous combination treatment. "In clinical practice, sequential treatment is most common," Dr. Jensen and Dr. Finnerup point out, "but in Gilron and colleagues' study, drugs in combination were given simultaneously." This study was supported by the Canadian Institutes of Health Research. Lead author Dr. Ian Gilron and senior author Dr. Robyn Houlden have disclosed receiving financial support from Pfizer. Editorialist Dr. Troels Jensen has disclosed that he has received funding from Pfizer, Eli Lilly, and Grunenthal. Editorialist Dr. Nanna Brix Finnerup has disclosed receiving research support from UCB Nordic. Lancet. Published online September 30, 2009. 加巴喷丁 【别  名】卡巴番定 , 加巴喷丁 【外文名】Gabapentin,Neurontin 【药理毒理】Gabapentin是美国Warner-Lanbert公司首先开发的抗癫痫药，于1993年首次在英国上市。加巴喷丁是一种新颖的抗癫痫药，它是γ－氨基丁酸（GABA）的衍生物，其药理作用与现有的抗癫痫药不同，最近研究表明加巴喷丁的作用是改变GABA代谢产生的。加巴喷丁在各种动物模型中均显示预防癫痫的作用，另外，在动物痉挛、镇痛和肌萎缩性测索硬化模型中也显示作用。加巴喷丁对脑组织的新颖结合点有高的亲和性，它能通过氨基酸转移体通过体内一些屏障，同其它抗惊厥药相比，加巴喷丁具有较小的行为和心血管副作用。 【药理作用】： 加巴喷丁抗惊厥作用的机制尚不明确，但动物试验提示，与其他上市的抗惊厥药物相似，加巴喷丁可抑制癫痫发作。小鼠和大鼠最大电休克试验、苯四唑癫痫发作试验以及其他动物试验（如遗传性癫痫模型等）结果提示，加巴喷丁具有抗癫痫作用，但这些癫痫模型与人体的相关性尚不清楚。 加巴喷丁在结构上与神经递质GABA相关，但不与GABA受体产生相互作用，它既不能代谢转化为GABA或GABA激动剂，也不是GABA摄取或降解的抑制剂。放射性配体结合试验发现，加巴喷丁浓度达到100μM时，对许多常见受体位点无亲和力，包括苯二氮受体、谷氨酸受体、NMDA受体、quisqualate受体、海人草酸受体、番木鳖碱-不敏感性或-敏感性的氨基乙酸受体、α1、α2或β受体、腺苷A1或A2受体、M或N受体、多巴胺D1或D2受体、H1受体、5-羟色胺S1或S2受体、阿片μ，δ或k受体、尼群地平或地尔硫标记的电压敏感钙通道位点、蛙毒素A　20-α-苯甲酸盐标记的电压敏感的钠通道位点。由于在评价药物对NMDA受体作用的几个常用试验所得出的结果是相反，故目前尚无任何关于加巴喷丁对NMDA受体作用的统一认识。 体外研究显示加巴喷丁在大鼠脑内的结合位点分布于新皮层和海马，其高亲和力的结合蛋白被证实为电压激活钙通道的辅助亚单位，相关功能尚未阐明。 【适应症】难治的不全性癫痫。有报道，抗焦虑药加巴喷丁（gabapentin）和抗病毒药伐昔洛韦（valacyclovir）联用可减少急性带状疱疹后遗神经痛的危险。 【不良反应】包括嗜睡，眩晕，行走不稳，疲劳感。这些副作用常见于用药早期。只要从小剂量开始，缓慢地增加剂量，多数人都能耐受。儿童偶尔会急躁易怒，停药以后会消失。 【用法用量】第一次睡前服300毫克。以后每天增加30毫克，用量可以高达每天3600毫克上述剂量需分三次服用。 【注意事项】对本药过敏者禁用。 【规格】胶囊：100mg/粒。300mg/片,400mg/片.

去甲替林
药物名称：去甲替林
药物别名：去甲阿米替林、Nortrllen，Pamelor，Sensival
英文名称：Nortriptyline
说　明： 片剂：10mg；25mg。
功用作用： 为阿米替林的代谢产物，具有抗抑郁作用，起效快适用于伴有紧张，焦虑的抑郁症患者。亦可用于焦虑状态。
用法用量： 口服：10mg，每日3～4次。需要时可渐增至25mg，每日3次。青少年、老年人10mg，tid。
注意事项：
（1）本品不良反应比丙米嗪少而且轻。常见有口干、嗜睡、便秘、视力模糊、排尿困难、心悸，偶见心律失常、眩晕、运动失调、癫痫样发作、体位性低血压、肝损伤及迟发性运动障碍。
（2）严重心脏病、青光眼及排尿困难者禁用。