Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia

Postherpetic neuralgia (PHN) is a chronic pain syndrome that disproportionately affects the elderly; its incidence is anticipated to increase as the population ages. PHN presents as pain (continuous burning or intense paroxysmal), most often with tactile allodynia, which may be severe and disabling, resulting in poor quality of life and depression. Traditional treatments have included tricyclic antidepressants, anticonvulsants and opioids; however, adverse systemic effects associated with these agents have led to the development of a newer and potentially safer agent, the topical lidocaine patch 5% (Lidoderm), a targeted peripheral analgesic.This article reviews the clinical pharmacology of the lidocaine patch 5% for the treatment of PHN and summarises data from clinical trials of its safety, tolerability and efficacy. The Medline search terms "lidocaine" and "patch" were used to search for English-language articles on the pharmacokinetics of the lidocaine patch 5% and its clinical use for the treatment of PHN. Additional published studies not identified by the database search but performed by the authors or their colleagues were also included in the review.The systemic absorption of lidocaine from the patch was minimal in healthy adults when four patches were applied for up to 24 hours/day, and lidocaine absorption was even lower among PHN patients than healthy adults at the currently recommended dose. Vehicle-controlled and open-label trials found the lidocaine patch 5%, either alone or in combination with other agents, to be effective in the treatment of PHN. Most adverse events were at patch application sites; no clinically significant systemic adverse effects were noted, including when used long term or in an elderly population.In patients with PHN, the lidocaine patch 5% has demonstrated relief of pain and tactile allodynia with a minimal risk of systemic adverse effects or drug-drug interactions. Because of its proven efficacy and safety profile, the lidocaine patch 5% has been recommended as a first-line therapy for the treatment of the neuropathic pain of PHN.     

Treatment of postherpetic neuralgia: an update

Postherpetic neuralgia (PHN) is a chronic pain syndrome that is often refractory to treatment and can last for years, causing physical and social disability, psychological distress, and increased use of the healthcare system. In this paper we provide an update on recent developments in the treatment of PHN. We emphasise the results of recent studies that provide an evidence-based approach for treating PHN that was not available until very recently. In randomised, controlled clinical trials, the topical lidocaine patch, gabapentin, and controlled release oxycodone have been shown to provide superior pain relief in patients with PHN when compared with placebo. It has also recently been demonstrated that the tricyclic antidepressant nortriptyline provides equivalent analgesic benefit when compared with amitriptyline, but is better tolerated. Based on these results, nortriptyline can now be considered the preferred antidepressant for the treatment of PHN, although desipramine may be used if the patient experiences unacceptable sedation from nortriptyline. The topical lidocaine patch, gabapentin and controlled release oxycodone all appear to be as effective as tricyclic antidepressants in the treatment of patients with PHN, and the results of these recent studies suggest that each of these treatments should be considered early in the course of treatment. Additional controlled trials are needed to compare the efficacy and tolerability of these 4 treatments- tricyclic antidepressants, gabapentin, the topical lidocaine patch and controlled release opioid analgesics--used singly and in various combinations in the treatment of patients with PHN.     

Post-herpetic neuralgia: a review of advances in treatment and prevention

Post-herpetic neuralgia (PHN) is primarily a disease of the elderly and often refractory to treatment. Randomized and controlled trials have yielded several significant advances in the treatment and prevention of this disease. Treatment advances include the lidocaine patch, opioid analgesics, nortriptyline, amitriptyline, and gabapentin. However, no treatment regimen fully eliminates the pain. Improvements in prevention include prompt recognition and treatment of high-risk herpes zoster (HZ) patients with antiviral and analgesic therapies. Even with these advances, PHN remains a debilitating and painful disease. Vaccines offer the greatest promise of relief. The childhood vaccine against varicella zoster virus offers long-lasting immunity, largely preventing HZ and PHN. But most adults have already had varicella and are at risk for HZ and PHN as they age. Therefore, a more potent vaccine against varicella has been developed for use in adults. This vaccine offers a new and significant advance in the prevention of HZ and its most noteworthy complication, PHN.     

Safety and efficacy outcomes of long-term treatment up to 4 years with 5% lidocaine medicated plaster in patients with post-herpetic neuralgia

Abstract Objective: Prospective evaluation of the long-term efficacy and safety of the 5% lidocaine medicated plaster in patients with post-herpetic neuralgia (PHN). Research design and methods: Patients with persisting pain for ≥3 months after acute herpes zoster and a baseline pain intensity of at least 4 on an 11-point numerical rating scale (NRS 0-10) were treated with 5% lidocaine medicated plasters for up to 5 years and monitored in regular intervals. Efficacy parameters are presented for the first 4 years and include patients' recall of pain relief (6-point verbal rating scale (VRS), clinical global impression of change (CGIC), patients' global impression of change PGIC), and the global evaluations of study medication. Safety parameters (clinical examination, skin evaluation, laboratory) and adverse events (AEs) were assessed at regular visits. Clinical trial registration: KF10004/02. Results: A total of 102 patients continuing from a 1 year main study period were included in an extension phase of up to 3 years. Ten patients (9.8%) dropped out due to lack of efficacy and 9 patients (8.8%) due to treatment-related AEs; 56 patients (54.9%) left the study for non-treatment-related reasons. Twenty-seven patients (26.4%) were still under treatment after a total treatment period of 4 years. On average, a pain relief of at least 4.3 (between moderate and a lot) was achieved throughout the study. At all visits the CGIC and the PGIC were much or very much improved in about 80% of patients. At the final visit, study medication was rated at least to be good by 91% of physicians and 89% of patients. Drug-related adverse events (DRAEs) were reported in 19 of 102 patients, mainly mild to moderate localized skin reactions. There were no hints for a reduced analgesic effect or an increase of DRAEs with long-term treatment. Conclusions: This study demonstrates that long-term treatment of ≥12 months with the 5% lidocaine medicated plaster is effective and well tolerated in PHN patients. These findings support the recommendations to use the 5% lidocaine medicated plaster as baseline therapy for localized neuropathic pain after herpes zoster infection (PHN).     

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.     

Post-herpetic neuralgia in older adults: evidence-based approaches to clinical management

Many individuals across the globe have been exposed to the varicella-zoster virus (VZV) that causes chickenpox. After chickenpox has resolved, the virus remains latent in the dorsal root ganglia where it can re-emerge later in life as herpes zoster, otherwise known as shingles. Herpes zoster is a transient disease characterised by a dermatomal rash that is usually associated with significant pain. Post-herpetic neuralgia (PHN) is the term used for the condition that exists if the pain persists after the rash has resolved. Advanced age and compromised cell-mediated immunity are significant risk factors for reactivation of herpes zoster and the subsequent development of PHN. Though the pathophysiology of PHN is unclear, studies suggest peripheral and central demyelination as well as neuronal destruction are involved. Both the vaccine against VZV (Varivax) and the newly released vaccine against herpes zoster (Zostavax) may lead to substantial reductions in morbidity from herpes zoster and PHN. In addition, current evidence suggests that multiple medications are effective in reducing the pain associated with PHN. These include tricyclic antidepressants, antiepileptics, opioids, NMDA receptor antagonists as well as topical lidocaine (lignocaine) and capsaicin. Reasonable evidence supports the use of intrathecal corticosteroids, but the potential for neurological sequelae should prompt caution with their application. Epidural corticosteroids have not been shown to provide effective analgesia for PHN. Sympathetic blockade may assist in treating the pain of herpes zoster or PHN. For intractable PHN pain, practitioners have performed delicate surgeries and attempted novel therapies. Although such therapies may help reduce pain, they have been associated with disappointing results, with up to 50% of patients failing to receive acceptable pain relief. Hence, it is likely that the most effective future treatment for this disease will focus on prevention of VZV infection and immunisation against herpes zoster infection with a novel vaccine.     

Topical lidocaine patch 5% may target a novel underlying pain mechanism in osteoarthritis

Recent literature and animal research has provided insight to potentially new analgesic targets for managing osteoarthritis (OA) pain. Primary afferent neurons located in affected joints express excessive amounts of abnormally functioning sodium (Na) channels on their surface in response to the inflammatory process. These Na channels may play an integral role in production of pain and hyperalgesia. Hence, the authors set out to conduct a 2-week, open-label, multicenter proof-of-concept study to evaluate the effectiveness and safety of lidocaine patch 5% monotherapy in adults with OA pain of the knee (n = 20). Patients with OA of one or both knees who were experiencing inadequate pain relief (defined as an average daily pain intensity of > 4 on a 0 to 10 pain scale) with their current analgesic regimen (i.e. APAP, NSAIDs, COX-2 inhibitors, tramadol) were enrolled and had all analgesic medications discontinued. Treatment with the lidocaine patch 5% resulted in significant improvements in the Western Ontario and McMaster Universities OA Index (WOMAC) pain, stiffness, physical function subscales and composite index (48.4, 41.1, 47.0, and 46.8% improvements respectively, p < 0.01). In addition, significant improvement was noted for pain intensity, pain relief, and pain interference with quality of life as measured by the Brief Pain Inventory (p < 0.05). The lidocaine patch 5% was generally well tolerated and no patients discontinued due to treatment-related adverse events. Given the open-label design, lack of a control group, and small sample size, the findings from our pilot study need to be confirmed by larger randomized controlled trials. Topical lidocaine patch 5% may provide clinicians with a novel, non-systemic therapy for OA pain with a unique mechanism of action.     

复方利多卡因乳膏联合芬太尼透皮贴剂治疗老年患者带状疱疹后遗神经痛的临床观察

目的：观察复方利多卡因乳膏联合芬太尼透皮贴剂治疗带状疱疹后遗神经痛的疗效。方法60例临床诊断为带状疱疹后遗神经痛患者随机分为三组（复方利多卡因组、芬太尼透皮贴剂组和复方利多卡因联合芬太尼透皮贴剂组）,利多卡因乳膏组：在最痛的皮肤区涂抹复方利多卡因乳膏,根据皮肤大小涂抹,保留时间最大不超过12 h,每次间隔时间大于12 h,每天涂抹次数不超过3次;芬太尼透皮贴剂组：使用芬太尼初始剂量为12．5μg·h－1,如疼痛控制不满意,逐渐增加剂量（每72 h增加12．5μg·h－1）;利多卡因乳膏联合芬太尼透皮贴剂组：使用芬太尼初始剂量为12．5μg·h－1,如疼痛控制不满意,在最痛的皮肤区涂抹复方利多卡因乳膏。观察并记录治疗前三组的VAS（视觉模拟尺）评分及治疗4周后三组的VAS评分、统计三组中的芬太尼及利多卡因用量、并发症。结果三组患者疼痛均获得了明显缓解（P＜0．05）,利多卡因乳膏联合芬太尼透皮贴剂组的治疗满意度与芬太尼透皮贴剂组及利多卡因乳膏组相比,有统计学差异（P＜0．05）。结论复方利多卡因乳膏联合芬太尼透皮贴剂治疗带状疱疹后遗神经痛取得了较好的疗效,值得临床推广。     

Treatment of postherpetic neuralgia

OBJECTIVE: To review treatment options for postherpetic neuralgia (PHN). DATA SOURCES: Clinical literature selected by the authors accessed via MEDLINE. Search terms included postherpetic neuralgia, capsaicin, antidepressants, anticonvulsants, and lidocaine. STUDY SELECTION: Controlled trials relevant to PHN. DATA SYNTHESIS: Traditional analgesics offer little benefit for the treatment of PHN. The best results for pain relief have come from capsaicin and tricyclic antidepressants. Anticonvulsants have also been used, although the number of studies evaluating this is limited. More invasive therapies, such as transcutaneous electrical nerve stimulation and nerve blocks, can be considered if other therapies fail. CONCLUSION: Early diagnosis and treatment of herpes zoster may offer patients the best chance of preventing the development of PHN. However, if PHN does develop, the patient should seek treatment early for the best chance of pain relief.     

Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy

ABSTRACT

Objective: Neuropathic pain is often difficult to treat due to a complex pathophysiology. This study evaluated the efficacy, tolerability and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN).

Methods: Patients completing 4-week monotherapy with 5% lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase. Patients with adequate response to monotherapy (recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [NRS-3 score]) continued their previous therapy, whereas those with insufficient response received combination therapy. Efficacy endpoints included change in NRS-3 from combination phase baseline, Patient and Clinical Global Impression of Change (PGIC/CGIC), and patient's satisfaction with treatment. Safety evaluation included adverse events (AEs), drug-related AEs (DRAEs), and withdrawal due to AEs.

Clinical trial registration: EudraCT No. 2006-003132-29.

Results: Of 229 patients in the per-protocol set (PPS: 68 PHN and 161 DPN), 71 received 5% lidocaine medicated plaster monotherapy, 57 had pregabalin added to 5% lidocaine medicated plaster, 57 pregabalin monotherapy and 44 received 5% lidocaine medicated plaster in addition to continued pregabalin treatment. There were no meaningful differences in demographic data between the treatment groups. Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores. Patients receiving combination therapy achieved clinically relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy. Improvement was similar between the two combination therapy groups. Considerable improvements in patients’ treatment satisfaction were reported. Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated.

Conclusions: In patients with PHN and painful DPN failing to respond to monotherapy, combination therapy with 5% lidocaine medicated plaster and pregabalin provides additional clinically relevant pain relief and is safe and well-tolerated.     

Topical lidocaine patch 5% may target a novel underlying pain mechanism in osteoarthritis

SUMMARY

Recent literature and animal research has provided insight to potentially new analgesic targets for managing osteoarthritis (OA) pain. Primary afferent neurons located in affected joints express excessive amounts of abnormally functioning sodium (Na) channels on their surface in response to the inflammatory process. These Na channels may play an integral role in production of pain and hyperalgesia. Hence, the authors set out to conduct a 2-week, open-label, multicenter proof-of-concept study to evaluate the effectiveness and safety of lidocaine patch 5% monotherapy in adults with OA pain of the knee (?n = 20). Patients with OA of one or both knees who were experiencing inadequate pain relief (defined as an average daily pain intensity of > 4 on a 0 to 10 pain scale) with their current analgesic regimen (i.e. APAP, NSAIDs, COX-2 inhibitors, tramadol) were enrolled and had all analgesic medications discontinued. Treatment with the lidocaine patch 5% resulted in significant improvements in the Western Ontario and McMaster Universities OA Index (WOMAC) pain, stiffness, physical function subscales and composite index (48.4, 41.1, 47.0, and 46.8% improvements respectively, p < 0.01). In addition, significant improvement was noted for pain intensity, pain relief, and pain interference with quality of life as measured by the Brief Pain Inventory (?p < 0.05). The lidocaine patch 5% was generally well tolerated and no patients discontinued due to treatment-related adverse events. Given the open-label design, lack of a control group, and small sample size, the findings from our pilot study need to be confirmed by larger randomized controlled trials. Topical lidocaine patch 5% may provide clinicians with a novel, non-systemic therapy for OA pain with a unique mechanism of action.     

Tolerability of treatments for postherpetic neuralgia.

Herpes zoster occurs in up to 20% of people infected with varicella-zoster virus, due to reactivation of the virus from latently infected sensory ganglia. Although pain is a typical feature of acute zoster, pain persisting for more than a month after resolution of the rash is less common and is termed postherpetic neuralgia (PHN). The pain associated with PHN is neuropathic in origin and is notoriously difficult to treat. The incidence of herpes zoster and its associated complications both increase with age, so PHN should be seen more commonly in an aging population. Vaccination with live, attenuated varicella vaccine is safe and efficacious, particularly in children. It decreases the incidence of acute varicella and subsequent herpes zoster. Aciclovir is well tolerated, with renal toxicity only at high intravenous doses. Treatment of acute varicella with aciclovir attenuates acute illness but does not prevent herpes zoster. Treatment of herpes zoster with aciclovir or its derivatives minimises symptoms and may reduce the rate of PHN. Foscarnet is an alternative for an aciclovir-resistant virus but its use is limited by renal and CNS toxicity. Corticosteroids reduce acute pain in herpes zoster but do not affect the incidence of PHN. Their use in some patients may be limited by adverse effects such as gastritis and impaired glucose tolerance. Treatment of established PHN is difficult and may require a holistic approach. Tricyclic antidepressants and gabapentin are the systemic agents with the most proven benefit, although opioids such as oxycodone and NMDA receptor antagonists such as ketamine may be useful in some people. Adverse effects from tricyclic antidepressants are common but usually mild, while gabapentin is generally well tolerated. Although effective, the relatively common adverse effects of opioids and ketamine limit their usefulness in treating PHN. Topical treatment with 5% lidocaine patch or capsaicin is of benefit in some patients and is generally well tolerated. Intrathecal methyl prednisolone may be considered for intractable pain but efficacy and safety have not been confirmed.     

Conclusions: chronic pain studies of lidocaine patch 5% using the Neuropathic Pain Scale

Many chronic pain patients have multiple etiologies for their pain, and accurate characterization of pain qualities and pain relief is essential for managing their pain. The ability to utilize a validated tool for assessing pain qualities and for identifying unique analgesic therapy effects on different pain qualities may assist clinicians in devising an appropriate treatment regimen. The Neuropathic Pain Scale (NPS) is a novel pain metric for characterizing pain in 10 dimensions. The ability to differentiate among pain qualities for each patient may result in a more refined and effective choice of therapy. The three research articles in this Supplement demonstrate the utility of the NPS in chronic pain patients treated with the lidocaine patch 5%, a peripherally acting medication that is not associated with systemic accumulation of the active drug. Significant reduction in the intensity of commonly reported pain qualities in patients with neuropathic and non-neuropathic chronic pain due to low-back pain, osteoarthritis, post-herpetic neuralgia, and painful diabetic neuropathy were achieved. The NPS offers clinicians a reliable means to accurately identify pain qualities associated with each individual patient and to target and assess the efficacy of various therapeutic options on those pain components. Utilizing the NPS, the lidocaine patch 5% was effective in treating chronic pain of both neuropathic and non-neuropathic origins suggesting that a given treatment's effect on various pain qualities may be consistent across pain types.     

Qutenza的药理和临床评价

 带状疱疹后神经痛(postherpetic neuralgia,PHN)是带状疱疹的严重并发症,在疱疹皮损消退后疼痛持续时间常常超过3个月。Qutenza(辣椒碱8%贴剂),为瞬时感受器电位香草酸受体1激动剂,能减轻PHN的疼痛。文中对Qutenza的作用机制、临床应用及不良反应等做一综述。     

Treatment of postherpetic neuralgia with 5% lidocaine medicated plaster in elderly patients – subgroup analyses from three European clinical trials

Objective: To investigate short- and long-term effectiveness and safety of the 5% lidocaine medicated plaster in the treatment of postherpetic neuralgia (PHN) in elderly patients (≥70 years of age).

Methods: Data from three European clinical trials was compared after stratification according to age (<70 years and ≥70 years). Length of study phase investigated was 4 weeks for study 1, 8 weeks for study 2, and up to 12 months for study 3. Effectiveness outcome measures were pain intensity, pain relief, allodynia severity, Clinical Global Impression of Change, and Patient Global Impression of Change. Safety was assessed by adverse event documentation.

Results: Mean average pain intensity improved in the elderly by ?2.1 (SD 2.1) vs. ?2.5 (SD 2.0) for <70 year old patients after 4 weeks, by ?1.4 (SD 1.8) vs. ?1.7 (SD 1.3) after 8 weeks, and by ?1.5 (SD 1.9) vs. ?2.7 (SD 2.2) after 12 months. Most patients presented with allodynia (>85% of elderly, >78% of younger patients) which was described by >51% as painful or extremely painful. Allodynia severity was markedly reduced in both groups during all three trials. Drug-related adverse events occurred in <20% of elderly and <15% of <70 year old patients and were mainly skin related.

Conclusions: The 5% lidocaine medicated plaster provided pain relief and marked reductions in allodynia severity in elderly PHN patients with an excellent safety profile under short- and long-term treatment supporting the addition of the plaster to the treatment armamentarium for this age group.

Study limitations: All analyzed study phases were open-label and lacking a placebo control group.     

5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label,non-inferiority two-stage RCT study

ABSTRACT

Objective: To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN).

Study design and methods: This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of ≥2 points or an absolute value of ≤4 points on the 11-point Numerical Rating Scale (NRS-3). Secondary endpoints included 30% and 50% reductions in NRS-3 scores; change in allodynia severity rating; quality of life (QoL) parameters EQ-5D, CGIC, and PGIC; patient satisfaction with treatment; and evaluation of safety (laboratory parameters, vital signs, physical examinations, adverse events [AEs], drug-related AEs [DRAEs], and withdrawal due to AEs).

Results: Ninety-six patients with PHN and 204 with painful DPN were analysed (full analysis set, FAS). Overall, 66.4% of patients treated with the 5% lidocaine medicated plaster and 61.5% receiving pregabalin were considered responders (corresponding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin.

Conclusion: 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and QoL compared with pregabalin for both indications, supporting its first line position in the treatment of localized neuropathic pain.     

Cost-effectiveness analysis of a lidocaine 5% medicated plaster compared with gabapentin and pregabalin for treating postherpetic neuralgia: a german perspective

OBJECTIVE: This study set out to assess the cost effectiveness of using a 5% lidocaine (lignocaine) medicated plaster for the treatment of postherpetic neuralgia (PHN) compared with gabapentin, pregabalin 300 mg/day or 600 mg/day in German primary care. The analysis took the perspective of the Statutory Health Insurance scheme (GKV). METHODS: A Markov model was used to calculate the costs (2007) and benefits of the lidocaine plaster, gabapentin 1800 mg/day and pregabalin 300 or 600 mg/day over a 6-month time horizon in elderly patients with PHN who experienced insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants. The model calculated the cost per quality-adjusted life-year (QALY) gained and the cost per additional month without symptoms or intolerable adverse effects. The majority of transition probabilities were obtained from randomized controlled trials identified from a systematic literature review. Further model inputs, including resource use, concomitant medication and long-term efficacy/adherence data, were obtained from a Delphi panel. Utility values were taken from a previous study and age adjusted. Cost data were obtained from official price tariffs. Mortality, indirect costs and costs associated with inpatient treatment were not considered in the present analysis due to the perspective and time horizon employed. RESULTS: Over the 6-month period modelled, the mean total therapy cost per patient treated with the lidocaine plaster was euro911, compared with euro728 for gabapentin, euro875 for pregabalin 300 mg/day and euro977 for pregabalin 600 mg/day. Treatment with the lidocaine plaster was related to greater numbers of QALYs and more months without symptoms or intolerable adverse effects (mean 0.300 QALYs and 4.06 months per patient) than with gabapentin (mean 0.247 QALYs and 2.72 months), pregabalin 300 mg/day (mean 0.253 QALYs and 3.02 months) or pregabalin 600 mg/day (mean 0.256 QALYs and 3.22 months). The lidocaine plaster cost euro3453/QALY gained and euro137 per additional month without adverse effects or symptoms relative to gabapentin and euro766/QALY and euro35 per month without adverse effects or symptoms relative to pregabalin 300 mg/day. The lidocaine plaster dominated pregabalin 600 mg/day, being less costly and more effective. Probabilistic sensitivity analysis indicated that there is a 99.36% chance that the lidocaine plaster is the most clinically effective treatment considered in the analysis and a 99.09% chance that the lidocaine plaster is the most cost-effective treatment of the four therapies considered in the analysis if the GKV is willing to pay at least euro20 000/QALY gained. Extensive deterministic sensitivity analyses demonstrated that the findings are robust. CONCLUSIONS: The 5% lidocaine-medicated plaster is a cost-effective treatment option for the management of PHN in Germany compared with gabapentin and both 300 and 600 mg/day of pregabalin.     

利多卡因减轻异丙酚注射痛最佳剂量研究

目的研究利多卡因减轻异丙酚注射痛最佳剂量。方法160例ASA评级Ⅰ-Ⅱ级择期行人工流产术女性患者,随机分为A、B、C、D共4组,每组40例,A组：预先推注利多卡因40mg后即推注异内酚150mg;B组、c组和D组均预先推注2ml生理盐水,之后B组推注10mg利多卡因与150mg异丙酚混合液;C组推注20mg利多卡因与异丙酚150mg混合液;D组推注40mg利多卡因与150mg异丙酚混合液。结果A组发生注射痛总计13例,占总数32％,B组发生注射痛总计11例．占总数27％,两者之间差异无统计学意义;C组和D组与A、B两组分别相比较均有统计学差异,C组与D组之间差异无统计学意义。结论利多卡因与异丙酚混合后注射的止痛效果要好于预先沌射,20mg利多卡因混合液为减轻异丙酚注射痛最佳剂量。     

Dental impaction pain model as a potential tool to evaluate drugs with efficacy in neuropathic pain

Intravenous lidocaine, a nonspecific Na-channel blocker, was used to assess the dental impaction model for evaluation of neuropathic pain drugs. Sixty patients, experiencing moderate or severe pain after removal of > or = 2 third molars, were randomized (2:2:1:1) to lidocaine (4 mg/kg; maximal dose 300 mg), oxycodone/acetaminophen (10/650 mg), placebo, and active placebo (diphenhydramine, 50 mg). Lidocaine provided a modest degree of pain relief. Predefined endpoints of total pain relief and sum of pain intensity at 2, 4, and 6 hours showed numerically, not statistically significantly, greater pain relief versus placebo. A significantly greater effect over placebo was observed in peak effect and at shorter time points (30 minutes and 1 hour), consistent with the pharmacokinetic profile (plasma concentration of approximately 2 mug/mL). Oxycodone/acetaminophen provided significantly greater analgesia versus placebo, validating study conduct, and significantly greater pain relief was observed versus lidocaine, which is consistent with a smaller portion of dental extraction pain being of neuropathic origin.