Extended-release gabapentin in post-herpetic neuralgia

INTRODUCTION: In early 2011, the FDA gave approval to a new preparation of gabapentin, licensed for the treatment of post-herpetic neuralgia (PHN). Gabapentin is commonly used worldwide for multiple indications, which include neuropathic pain. The new drug combines generic gabapentin with a polymeric delivery system allowing for extended release and is licensed to be given only as a once-daily dosing regimen. AREAS COVERED: The article aims to review the available evidence relating to the pharmacokinetics, tolerability and efficacy of extended-release gabapentin (GpER). It addresses the current state of the drug's progress through regulation and the intention of its manufacturer for the market. EXPERT OPINION: Although GpER has been approved by the FDA for once-daily use in PHN, there is a relative paucity of data for both its efficacy and the optimum dosing schedule (once or twice a day). There are no data directly comparing GpER with the immediate-release preparation or other first-line treatments for PHN. Therefore, the true status of GpER as a treatment option needs to be enhanced with additional experimental evidence for its efficacy and favourable side-effect profile.     

多柔吡星注射剂治疗带状疱疹后遗神经痛的临床研究

目的观察多柔吡星注射剂治疗带状疱疹后遗神经痛的临床疗效及安全性。方法将104例带状疱疹后遗神经痛患者随机分为对照组52例和试验组52例。对照组予以脉冲射频治疗,每周2次,每次3 min;试验组予以多柔吡星每次10 mg,每2周1次,经椎间孔注射。2组患者均治疗4周。比较2组患者的临床疗效、视觉模拟评分法(VAS)评分、血清中白细胞介素-6(IL-6)和IL-10水平,以及药物不良反应的发生情况。结果治疗后,试验组和对照组的总有效率分别为86.54%(45例/52例)和69.23%(36例/52例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组血清中IL-6分别为(174.83±23.72)和(321.65±45.82)pg·mL^-1,IL-10分别为(183.46±28.11)和(164.67±21.31)μg·mL^-1,VAS评分分别为(2.32±0.65)和(3.51±0.84)分,差异均有统计学意义(均P<0.05)。试验组的药物不良反应主要有阻滞区皮肤麻木和心慌,对照组未发生药物不良反应。试验组和对照组的总药物不良反应发生率为5.77%和0,差异无统计学意义(P>0.05)。结论多柔吡星注射剂治疗带状疱疹后遗神经痛的临床疗效确切,促进炎性因子平衡,有效改善患者的疼痛症状,且不增加药物不良反应的发生率。     

Extended-release gabapentin in post-herpetic neuralgia

Introduction: In early 2011, the FDA gave approval to a new preparation of gabapentin, licensed for the treatment of post-herpetic neuralgia (PHN). Gabapentin is commonly used worldwide for multiple indications, which include neuropathic pain. The new drug combines generic gabapentin with a polymeric delivery system allowing for extended release and is licensed to be given only as a once-daily dosing regimen.

Areas covered: The article aims to review the available evidence relating to the pharmacokinetics, tolerability and efficacy of extended-release gabapentin (GpER). It addresses the current state of the drug's progress through regulation and the intention of its manufacturer for the market.

Expert opinion: Although GpER has been approved by the FDA for once-daily use in PHN, there is a relative paucity of data for both its efficacy and the optimum dosing schedule (once or twice a day). There are no data directly comparing GpER with the immediate-release preparation or other first-line treatments for PHN. Therefore, the true status of GpER as a treatment option needs to be enhanced with additional experimental evidence for its efficacy and favourable side-effect profile.     

普瑞巴林治疗带状疱疹后神经痛的临床疗效观察

目的观察普瑞巴林治疗带状疱疹后神经痛的临床疗效和安全性。方法带状疱疹后神经痛患者80例,采用随机对照,分为治疗组和对照组,治疗组(n=40)给予普瑞巴林口服150 mg.d-1,对照组(n=40)给予卡马西平600 mg.d-1,观察时间为4周。采用视觉模拟评分(VAS)评估治疗前及治疗后1、2、3、4周疼痛程度,采用中国版生活质量量表(SF-36)对两组患者治疗前和治疗后4周生活质量情况进行评定,同时观察治疗期间McGill疼痛问卷简表(SF.MPQ)分值的改变、持续睡眠时间及不良反应。结果经过4周的治疗,治疗组较对照组疼痛程度明显减轻(P0.05),睡眠和生活质量改善情况优于对照组(P0.05),且不良反应相对较少(P0.05)。结论普瑞巴林可明显减轻带状疱疹后神经痛患者疼痛,改善生活质量。     

椎旁阻滞联合右美托咪定治疗带状疱疹后神经痛的临床疗效分析

目的观察椎旁注射联合右美托咪定(Dex)治疗带状疱疹后神经痛(PHN)的临床效果。方法在我科治疗PHN患者共60例,平均分为对照组和Dex组;对照组采用传统椎旁注射局麻药+糖皮质激素的方法,Dex组在对照组的基础上增加右美托咪定1μg/kg。分别观察治疗前、治疗中及治疗结束后1周、4周时的视觉模拟评分(VAS),匹兹堡睡眠质量指数(PSQI)评分,以及CD4+、CD8+和CD4+/CD8+。结果与对照组比较,Dex组在治疗中椎旁注射第3次以及治疗后第4周,VAS评分明显降低(P<0.05);Dex组睡眠质量明显增高(PSQI:10.05±1.88与12.71±1.93,P<0.05);与对照组相比较,Dex组能有效减轻患者免疫抑制(治疗后第1周CD4+/CD8+:1.68±0.14与1.46±0.12,P<0.01;治疗后第4周CD4+/CD8+:1.64±0.13与1.56±0.16,P<0.05)。结论椎旁阻滞联合Dex治疗PHN效果显著,并且与传统的椎旁阻滞联合激素治疗相比较,使用Dex可以改善患者睡眠、提高免疫功能、更快的促进患者康复。     

普瑞巴林联合强的松治疗带状疱疹后神经痛的疗效及安全性

目的 探讨普瑞巴林与强的松联合应用治疗带状疱疹神经痛患者的临床疗效及安全性.方法 选取2010年3月至2013年3月我院收治的带状疱疹后神经痛患者64例,按其就诊顺序均分为对照组及观察组,每组32例.对照组给予口服普瑞巴林,观察组给予普瑞巴林联合强的松治疗.比较两组的临床疗效及安全性.结果 治疗后3周,对照组疼痛发生率、疼痛程度评分、精神状况评分、不良反应发生率分别为56.25％、5.8±0.5、5.3±1.6、9.4％,观察组分别为28.12％、3.6±1.1、4.8±1.8、3.1％,两组比较,差异均具有统计学意义（P均＜ 0.05）;治疗9周后,对照组患者疼痛发生率、疼痛程度、精神状况、不良反应发生率为50.0％、2.8±0.9、3.1±0.9、12.5％,观察组为9.38％、0.9±0.06、2.3±0.6、6.25％,两组比较差异均具有统计学意义（P＜0.01或P＜0.05）.结论 普瑞巴林联合强的松治疗带状疱疹后神经痛疗效显著优于单用普瑞巴林,且不良反应发生率低于单用普瑞巴林,值得临床推广.     

神经阻滞联合微波治疗带状疱疹后遗神经痛的临床研究

目的观察神经阻滞联合微波治疗带状疱疹后遗痛的疗效。方法选择80例带状疱疹后遗痛患者，随机分为两组，A组采用维生素B12维生素B1联合消炎痛治疗；B组采用神经阻滞联合微波治疗。分别于治疗后1d，3d，7d，14d用视觉模拟评分法（VAS）对两组患者疼痛和睡眠程度进行评分。结果两组患者经治疗后，VAS评分有显著性差异（P〈0．001），B组患者的止痛效果和睡眠质量明显优于A组。结论神经阻滞联合微波治疗带状疱疹后遗神经痛，疗效显著而安全。     

The potential cost-effectiveness of vaccination against herpes zoster and post-herpetic neuralgia

A clinical trial has shown that a live-attenuated varicella-zoster virus vaccine is effective against herpes zoster (HZ) and post-herpetic neuralgia (PHN). The aim of this study was to examine the cost-effectiveness of vaccination against HZ and PHN in Canada. A cohort model was developed to estimate the burden of HZ and the cost-effectiveness of HZ vaccination, using Canadian population-based data. Different ages at vaccination were examined and probabilistic sensitivity analysis was performed. The economic evaluation was conducted from the ministry of health perspective and 5% discounting was used for costs and benefits. In Canada (population = 30 million), we estimate that each year there are 130,000 new cases of HZ, 17,000 cases of PHN and 20 deaths. Most of the pain and suffering is borne by adults over the age of 60 years and is due to PHN. Vaccinating 65-year-olds (HZ efficacy = 63%, PHN efficacy = 67%, no waning, cost/course = $150) is estimated to cost $33,000 per QALY-gained (90% CrI: 19,000-63,000). Assuming the cost per course of HZ vaccination is $150, probabilistic sensitivity analysis suggest that vaccinating between 65 and 75 years of age will likely yield cost-effectiveness ratios below $40,000 per Quality-Adjusted Life-Year (QALY) gained, while vaccinating adults older than 75 years will yield ratios less than $70,000 per QALY-gained. These results are most sensitive to the duration of vaccine protection and the cost of vaccination. In conclusion, results suggest that vaccinating adults between the ages of 65 and 75 years is likely to be cost-effective and thus to be a judicious use of scarce health care resources.     

加巴喷丁与曲马多联用缓解老年患者带状疱疹后遗神经疼痛临床研究

目的探讨加巴喷丁与曲马多联用缓解老年患者带状疱疹后遗神经疼痛的临床效果及安全性。方法选择我院2011年6月至2014年6月带状疱疹后遗神经疼痛老年患者170例,采用随机抽样方法分为对照组和试验组,每组85例;两组患者入院后均采用常规对症支持治疗;对照组患者采用盐酸曲马多单用口服治疗;试验组患者则采用盐酸曲马多与加巴喷丁联用口服治疗。比较两组患者疼痛缓解疗效,治疗前后视觉模拟评价量表评分(VAS)、匹兹堡睡眠质量评分(PSQI)及不良反应发生率等。结果对照组和试验组患者疼痛缓解显效率分别为30.59%、52.94%,临床治疗总有效率分别为63.53%、95.29%,两组比较差异有统计学意义(P<0.05)。治疗后两组VAS评分降低,且试验组低于对照组,差异有统计学意义(P<0.05);治疗后两组PSQI评分升高,且试验组高于对照组,差异有统计学意义(P<0.05)。两组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论加巴喷丁与曲马多联用于老年带状疱疹后遗神经疼痛,可有效降低疼痛程度,提高睡眠质量,且不增加不良反应发生风险,疗效及安全性良好。     

普瑞巴林治疗带状疱疹后神经痛的临床观察

目的:观察普瑞巴林治疗带状疱疹后神经痛(post-herpetic neuralgia,PHN)的有效性和安全性。方法:52例PHN患者随机分为两组,对照组(n=26)采用传统药物治疗,治疗组(n=26)采用普瑞巴林,剂量从150 mg·d-1起,根据服药后患者疼痛的缓解程度以及不良反应予以调整,疗程4周。采用数字疼痛评分量表(NRS)评估用药前及第1,2和4周的疼痛程度。结果:两组用药后NRS评分均降低,普瑞巴林组治疗后1,2和4周的NRS评分明显低于对照组。普瑞巴林组不良反应较少且轻微,主要表现为头晕和嗜睡。结论:普瑞巴林治疗带状疱疹后神经痛有效且安全。     

胸椎旁注射治疗带状疱疹后神经痛

目的研究胸椎旁注射治疗胸背部带状疱疹后神经痛的疗效。方法胸背部带状疱疹后神经痛患者30例,给予胸椎旁注射,药物：神经妥乐平、得宝松、利多卡因、罗哌卡因。每周1次,共4周。记录治疗前后的VAS值,匹兹堡睡眠质量指数PSQI,是否存在痛觉超敏以及治疗过程中的不良反应。结果与治疗前比较,VAS值和PSQI均显著降低（P〈0.01）;VAS值：前3次注射每次均较上一次显著降低,但第4次与第3次比较,差异无统计学意义;痛觉超敏缓解率为78.26%;胸椎旁注射治疗中和治疗后未出现明显不良反应。结论胸椎旁注射治疗带状疱疹后神经痛疗效确切,安全可行。但3次以上的治疗则无必要。     

胸椎旁注射治疗带状疱疹后神经痛

目的研究胸椎旁注射治疗胸背部带状疱疹后神经痛的疗效。方法胸背部带状疱疹后神经痛患者30例,给予胸椎旁注射,药物:神经妥乐平、得宝松、利多卡因、罗哌卡因。每周1次,共4周。记录治疗前后的VAS值,匹兹堡睡眠质量指数PSQI,是否存在痛觉超敏以及治疗过程中的不良反应。结果与治疗前比较,VAS值和PSQI均显著降低(P<0.01);VAS值:前3次注射每次均较上一次显著降低,但第4次与第3次比较,差异无统计学意义;痛觉超敏缓解率为78.26%;胸椎旁注射治疗中和治疗后未出现明显不良反应。结论胸椎旁注射治疗带状疱疹后神经痛疗效确切,安全可行。但3次以上的治疗则无必要。     

Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain

Introduction: Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option.

Areas covered: This report summarizes both published and unpublished results of clinical trials with AmiKet. In post-herpetic neuralgia (PHN), AmiKet produces a significant analgesia which is comparable to that produced by oral gabapentin. In diabetic painful neuropathy, AmiKet showed a strong trend towards pain reduction. In mixed neuropathic pain, case series reports suggest a favourable response rate, but are limited by trial characteristics. AmiKet is absorbed minimally following topical administration. Over 700 patients have now received topical AmiKet in clinical regimens, and it is well-tolerated with the adverse effects mainly being application site reactions. Both agents are polymodal, and several mechanisms may contribute to the peripheral efficacy of AmiKet.

Expert opinion: Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination.     

An update on the pharmacological management of post-herpetic neuralgia and painful diabetic neuropathy

Neuropathic pain is a persistent pain condition that develops secondary to nerve injury. The two most common types of peripheral neuropathic pain are post-herpetic neuralgia (PHN) and painful diabetic neuropathy (PDN). Amitriptyline, nortriptyline, desipramine and imipramine are TCAs that have been shown to be effective for the symptomatic relief of PHN and PDN. Serotonin noradrenaline reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine have been shown to be very promising for the treatment of PDN with fewer adverse effects than TCAs. Selective serotonin reuptake inhibitors (SSRIs) were shown in a number of studies to have some efficacy in relieving PDN-related pain, yet other studies of the SSRIs have demonstrated conflicting outcomes. Most of the older antiepileptic studies were performed in patients with PDN; consequently, little is known about the efficacy of these drugs in patients with PHN. Carbamazepine, phenytoin and valproic acid were shown to be effective in ameliorating PDN-related pain. Other antiepileptic agents, including lamotrigine, oxcarbazepine and topiramate, have demonstrated some beneficial effects for the treatment of PDN, although they were also found to be ineffective in some PDN studies. alpha2delta Ligands such as gabapentin and pregabalin have been proven to be effective for the treatment of PHN and PDN in a number of large placebo-controlled trials. These drugs are useful not only in relieving pain but also in improving quality of life. Although the use of opioids for the treatment of neuropathic pain is controversial, a number of studies support the efficacy and safety of opioids in the treatment of neuropathic pain. Of these, oxycodone and tramadol have been shown to be superior to placebo for the treatment of PHN and PDN. A number of small studies have shown that dextromethorphan was effective in patients with PDN but not in patients with PHN. Topical agents such as lidocaine 5% patches and topical capsaicin are useful in ameliorating pain in patients with PHN but these agents are unsatisfactory for use as a sole agent. Although a number of drug treatments are available for the symptomatic relief of neuropathic pain symptoms, these agents do not provide satisfactory relief in all patients. For these patients, other treatment alternatives such as combination drug therapy that produces pain relief via distinctly different mechanisms may be successful. The purpose of this review is to compare the efficacy and limitations of currently available pharmacological treatments for the symptomatic relief of PHN and PDN, and to discuss the potential of combination therapy in PHN and PDN.     

中药联合针灸治疗带状疱疹后遗神经痛的疗效探究

目的 探究带状疱疹后遗神经痛患者采取针灸联合中药内服方案治疗的临床效果.方法 80例带状疱疹后遗神经痛患者,根据随机数字表法分为对照组与观察组,各40例.对照组提供常规西药对症治疗,观察组给予针灸联合中药方案治疗,比较两组患者疼痛改善效果以及睡眠质量改善效果.结果 观察组疼痛改善总有效率92.5％高于对照组的75.0％...     

The cost effectiveness of infliximab for severe treatment-resistant rheumatoid arthritis in the UK

OBJECTIVE: To estimate the cost effectiveness (from the UK NHS and personal social service perspectives) of infliximab plus methotrexate (MTX) compared with MTX alone, in the treatment of patients with severe rheumatoid arthritis (RA) who were not adequately controlled on disease-modifying antirheumatic drugs and who were resistant to MTX. METHOD: Clinical data for the first year of therapy were taken from the ATTRACT (Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy) and a Markov model developed to assess costs and consequences in the longer term. Transition probabilities and health state valuations for the model were estimated based on the ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) cohort, and resource use and costs ( 2,000 pounds values) obtained from various sources in the UK. Univariate sensitivity analyses were conducted to test the robustness of the results. RESULTS: The primary analysis suggested that infliximab plus MTX had an ICER of 33,618 pounds per QALY gained. Alternative modelling assumptions and various other sensitivity analyses were applied, but the ICER always remained within the range for interventions typically funded by the NHS. CONCLUSION: This model suggests, with its underlying assumptions and data, that the combination of infliximab and MTX may be a cost-effective treatment (from the UK NHS and personal social service perspectives) for patients experiencing RA that cannot be maintained on MTX alone.     

Double-blind, placebo-controlled clinical trial of a mixture of gangliosides ('Cronassial') in post-herpetic neuralgia

A double-blind, parallel-group clinical trial was carried out in 25 patients with post-herpetic neuralgia to determine the efficacy and tolerability of a mixture of gangliosides ('Cronassial') compared with placebo. Patients were allocated at random to receive treatment with either 'Cronassial' (100 mg in 2 ml buffered solution) or placebo given by 11 subcutaneous injections over a period of 27 days, and their symptoms assessed on entry and after 2, 4 and 8 weeks. The four aspects of pain considered (overall pain, hyperaesthesia, stabbing pain and constant ache) all showed maintained reductions in severity with 'Cronassial' treatment, but not with placebo. In the case of hyperaesthesia, this difference between treatments was statistically significant (both during and after the course of injections), even with the relatively small number of patients in this study. Sleep patterns showed significant sustained improvements with 'Cronassial', but not with placebo treatment. Other psychological assessments (general psychological state, appetite and mood) showed little difference between 'Cronassial' and placebo treatment. Although 'Cronassial' was well tolerated systemically, 1 of the 12 patients was withdrawn because of general malaise, and 5 patients had local pain at the injection sites. Two of these 5 patients were withdrawn from the study. There were no withdrawals in the placebo group. It is suggested that further studies employing greater numbers of patients should be carried out to confirm the efficacy of gangliosides in improving symptoms of patients with post-herpetic neuralgia.