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Zhao C, Shrestha N, Ren H, Zhang B, Shen Y, Meng L, Wu D, Wang B, Fan B, Luo F. The PATCH trial: 5% lidocaine-medicated plaster for trigeminal neuralgia-Results of a multicentric, enriched enrollment, randomized withdrawal, double-blind, vehicle-controlled, parallel-group study. Headache 2024; 64:1318-1328. [PMID: 39193836 DOI: 10.1111/head.14814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 05/22/2024] [Accepted: 05/30/2024] [Indexed: 08/29/2024]
Abstract
OBJECTIVE To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN). BACKGROUND TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN. METHODS The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study. RESULTS The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007). CONCLUSIONS LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.
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Affiliation(s)
- Chunmei Zhao
- Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Niti Shrestha
- Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Hao Ren
- Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Baohui Zhang
- Department of Pain Management, Linfen People's Hospital, Linfen, Shanxi, China
| | - Ying Shen
- Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Lan Meng
- Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Dasheng Wu
- Department of Pain Management, Jilin Province People's Hospital, Jilin, China
| | - Baoguo Wang
- Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing, China
| | - Bifa Fan
- National Pain Management & Research Center, China-Japan Friendship Hospital, Beijing, China
| | - Fang Luo
- Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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Wang A, Li H, Xie Z, Li L, Jiang X, Guo Q, Hu F, Zhang J, Cui Y, Ding Y, Fang H, Han X, Guo S, Wang J, Ni N. Randomized, Placebo-Controlled, Multicenter Clinical Study on the Efficacy and Safety of Lidocaine Patches in Chinese Patients with Postherpetic Neuralgia. Dermatol Ther (Heidelb) 2023:10.1007/s13555-023-00938-8. [PMID: 37268784 DOI: 10.1007/s13555-023-00938-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 05/09/2023] [Indexed: 06/04/2023] Open
Abstract
INTRODUCTION To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). METHODS Patients were randomized to receive lidocaine patches or placebo every day for 4 weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. RESULTS Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. CONCLUSIONS Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.
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Affiliation(s)
- Aiping Wang
- Dermatology and Venereology Department, Peking University First Hospital, Beijing, China
| | - Hang Li
- Dermatology and Venereology Department, Peking University First Hospital, Beijing, China.
| | - Zhihong Xie
- Dermatology Department, Beijing Hospital, Beijing, China
| | - Lingfeng Li
- Dermatology and Venereology Department, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xian Jiang
- Dermatology and Venereology Department, West China Hospital, Sichuan University, Chengdu, China
| | - Qing Guo
- Dermatology Department, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Fengming Hu
- Department of Integrated Chinese and Western Medicine, Dermatology Hospital of Jiangxi Province, Nanchang, China
| | - Jianzhong Zhang
- Dermatology Department, Peking University People's Hospital, Beijing, China
| | - Yong Cui
- Dermatology Department, China-Japan Friendship Hospital, Beijing, China
| | - Yangfeng Ding
- Dermatology Department, Shanghai Skin Disease Hospital, Shanghai, China
| | - Hong Fang
- Dermatology Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiuping Han
- Dermatology Department, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shuping Guo
- Dermatology Department, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Junlong Wang
- Clinical Research Center, China State Institute of Pharmaceutical Industry, Shanghai, China
| | - Na Ni
- Clinical Research Center, China State Institute of Pharmaceutical Industry, Shanghai, China
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Sabatschus I, Bösl I, Prevoo M, Eerdekens M, Sprünken A, Galm O, Forstner M. Comparative Benefit-Risk Assessment for Lidocaine 700 mg Medicated Plaster and Pregabalin in Peripheral Neuropathic Pain Following a Structured Framework Approach. Pain Ther 2021; 11:73-91. [PMID: 34792789 PMCID: PMC8861254 DOI: 10.1007/s40122-021-00340-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/05/2021] [Indexed: 11/24/2022] Open
Abstract
Introduction Peripheral neuropathic pain (PNP) is difficult to treat. Several oral drugs are recommended as first-line treatments. Nevertheless, many patients cannot obtain sufficient pain relief or do not tolerate systemically active treatments. Topical treatments, with a lower risk of systemic side effects such as lidocaine 700 mg medicated plaster, are also recommended in treatment guidelines. This analysis compares the benefit–risk balance of topical 700 mg lidocaine medicated plaster with the benefit–risk balance of oral pregabalin administration for the treatment of PNP following current recommendations on benefit–risk assessment (BRA) methodology. Methods The Benefit–Risk Action Team (BRAT) framework was used as structured approach. Selection of key benefits and risks was supported by a patient survey. Published randomized controlled clinical trials were the main source to identify data related to key benefits and risks. The outcome of randomized clinical trials was compared with real-world evidence (RWE) data for consistency. Results Identified key benefits were pain reduction and improvement in quality of life. Key risks identified were application site reactions, dizziness, confusion, weight gain, peripheral edema, and blurred vision. Overall, there was similarity in key benefits between the comparators; however, a clear advantage regarding key risks in favor of lidocaine 700 mg medicated plaster was observed. This observation was consistent across data from a direct comparison trial, randomized placebo-controlled trials, as well as data from RWE studies. The low number of randomized controlled trials for lidocaine 700 mg medicated plaster was the main limitation. Conclusion Guided by the opinion of patients regarding key benefits and risks deemed important for treatments of peripheral neuropathic pain, our analysis showed that lidocaine 700 mg medicated plaster has a more favorable benefit–risk balance compared to pregabalin (300 and 600 mg daily). Supplementary Information The online version contains supplementary material available at 10.1007/s40122-021-00340-2.
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Voute M, Morel V, Pickering G. Topical Lidocaine for Chronic Pain Treatment. Drug Des Devel Ther 2021; 15:4091-4103. [PMID: 34616143 PMCID: PMC8487862 DOI: 10.2147/dddt.s328228] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 08/20/2021] [Indexed: 12/21/2022] Open
Abstract
Topical lidocaine is widely used in current practice for a variety of pain conditions. This literature review shows that its limited absorption and relative lack of systemic adverse events are an attractive analgesic option for a number of vulnerable patients. Topical lidocaine has been approved by health authorities for the treatment of post-herpetic neuralgia in a number of countries, and studies present some degree of evidence of its efficacy and safety in postsurgical pain, diabetic peripheral neuropathy, carpal tunnel syndrome, chronic lower back pain and osteoarthritis. Topical lidocaine may be a great alternative alone or in addition to systemic drugs and non-pharmacological approaches for an optimized pain management and in multimodal analgesia.
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Affiliation(s)
- Marion Voute
- CHU Clermont-Ferrand, Plateforme d'Investigation Clinique - Centre d'Investigation Clinique, CIC Inserm 1405, Clermont-Ferrand, F-63000, France
| | - Véronique Morel
- CHU Clermont-Ferrand, Plateforme d'Investigation Clinique - Centre d'Investigation Clinique, CIC Inserm 1405, Clermont-Ferrand, F-63000, France
| | - Gisèle Pickering
- CHU Clermont-Ferrand, Plateforme d'Investigation Clinique - Centre d'Investigation Clinique, CIC Inserm 1405, Clermont-Ferrand, F-63000, France.,Université Clermont Auvergne, Inserm 1107, Clermont-Ferrand, F-63000, France
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Dapsone Prevents Allodynia and Hyperalgesia and Decreased Oxidative Stress After Spinal Cord Injury in Rats. Spine (Phila Pa 1976) 2021; 46:1287-1294. [PMID: 34517396 DOI: 10.1097/brs.0000000000004015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Prospective longitudinal experimental study. OBJECTIVE We evaluate the effect of dapsone on tactile allodynia and mechanical hyperalgesia and to determine its anti-oxidant effect in a spinal cord injury (SC) model in rats. SUMMARY OF BACKGROUND DATA Neuropathic pain (NP) as result of traumatic spinal cord injury is a deleterious medical condition with temporal or permanent time-course. Painful stimuli trigger a cascade of events that activate the N-methyl-D-aspartate (NMDA) receptor, inducing an increase in oxidative stress. Since there is no effective treatment for this condition, dapsone (4,4'diaminodiphenylsulfone) is proposed as potential treatment for NP. Its anti-oxidant, neuroprotective, and anti-inflammatory properties have been documented, however, there is no evidence regarding its use for treatment of NP induced by SCI. METHODS In this study, we evaluated the anti-allodynic and anti-hyperalgesic effect of dapsone as preventive or acute treatment after NP was already established. Furthermore, participation of oxidative stress was evaluated by measuring lipid peroxidation (LP) and glutathione concentration (GSH) in rats with SCI. RESULTS Acute treatment with dapsone (3.1-25 mg/kg, i.p.) decreased nociceptive behaviors in a dose-dependent manner, decreased LP, and increased GSH in the injured tissue 15 days after the injury was produced. On the other hand, preventive treatment (3 h post-injury, once daily for 3 days) with dapsone (3.1-25 mg/kg, i.p.) yielded similar results. CONCLUSION The findings suggest that the anti-nociceptive effect of dapsone is regulated through the decrease of oxidative stress and the excitotoxicity is associated with the activation of NMDA receptors.Level of Evidence: N/A.
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Überall MA, Eerdekens M, Hollanders E, Bösl I, Sabatschus I. Lidocaine 700 mg medicated plaster for postherpetic neuralgia: real-world data from the German Pain e-Registry. Pain Manag 2021; 12:195-209. [PMID: 34372662 DOI: 10.2217/pmt-2021-0022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Aim: To provide real-world evidence for the effectiveness and tolerability of lidocaine 700 mg medicated plaster (LMP) compared with oral systemic first-line medications (OSM) in postherpetic neuralgia treatment. Patients & methods: Retrospective cohort study in patients refractory to at least one recommended OSM (single drug or a combination of drugs) using anonymized routine medical care data from the German Pain e-Registry. A matched pair approach using propensity score matching was employed. Results: A total of 1711 data sets of postherpetic neuralgia patients were identified per treatment group. The majority (>60%) had experienced pain for more than a year and reported a high burden of pain and reduced quality of life. Six months of LMP treatment provided significantly greater pain reductions, improvements in pain-related impairments and quality of life than OSM treatment (p < 0.001 for all parameters). Drug-related adverse events and treatment discontinuation due to drug-related adverse events also occurred less frequently under LMP treatment (p < 0.001). Conclusion: These real-world data confirm the effectiveness and good tolerability of LMP under routine medical care. The treatment was significantly more effective when compared with first-line oral systemic medications.
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Ma K, Jiang W, Wang YX, Wang L, Lv Y, Liu JF, Liu RG, Liu H, Xiao LZ, Du DP, Lu LJ, Yang XQ, Xia LJ, Huang D, Fu ZJ, Peng BG, Liu YQ. Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch. World J Clin Cases 2021; 9:2110-2122. [PMID: 33850930 PMCID: PMC8017498 DOI: 10.12998/wjcc.v9.i9.2110] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/14/2021] [Accepted: 03/09/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic pain lasting more than 3 mo, or even several years can lead to disability. Treating chronic pain safely and effectively is a critical challenge faced by clinicians. Because administration of analgesics through oral, intravenous or intramuscular routes is not satisfactory, research toward percutaneous delivery has gained interest. The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area. It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery, which reduces the dose frequency and side effects. If not required, then the patch can be removed from the skin immediately. The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979. From then on, the transdermal patch has been widely used to treat many diseases. To date, no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery. The pain branch of the Chinese Medical Association, after meeting and discussing with experts and based on clinical evidence, developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.
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Affiliation(s)
- Ke Ma
- Department of Algology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Wei Jiang
- Department of Anesthesiology, Third Medical Center of People’s Liberation Army General Hospital, Beijing 100039, China
| | - Yun-Xia Wang
- Department of Algology, The Third People’s Hospital of Hubei Province, Hubei Zhongshan Hospital, Wuhan 430033, Hubei Province, China
| | - Lin Wang
- Department of Algology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
| | - Yan Lv
- Department of Algology, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Jin-Feng Liu
- Department of Algology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Rong-Guo Liu
- Department of Algology, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
| | - Hui Liu
- Department of Algology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Li-Zu Xiao
- Department of Algology, Shenzhen Sixth People’s Hospital (Nanshan Hospital), Shenzhen 518000, Guangdong Province, China
| | - Dong-Ping Du
- Department of Algology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China
| | - Li-Juan Lu
- Department of Algology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Xiao-Qiu Yang
- Department of Algology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Ling-Jie Xia
- Department of Algology, Henan Provincial People’s Hospital, Zhengzhou 450000, Henan Province, China
| | - Dong Huang
- Department of Algology, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Zhi-Jian Fu
- Department of Algology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Bao-Gan Peng
- Department of Orthopedics, The Third Medical Center, General Hospital of the Chinese People’s Liberation Army, Beijing 100039, China
| | - Yan-Qing Liu
- Department of Algology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
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Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review. Pharmaceutics 2021; 13:pharmaceutics13040450. [PMID: 33810493 PMCID: PMC8067282 DOI: 10.3390/pharmaceutics13040450] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/17/2021] [Accepted: 03/22/2021] [Indexed: 12/25/2022] Open
Abstract
Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients' quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences. Moreover, topical treatments applied locally may target the underlying mechanisms of peripheral sensitization and pain. Recent studies showed that peripheral sensitization results from interactions between neuronal and non-neuronal cells, with numerous signaling molecules and molecular/cellular targets involved. This narrative review discusses the molecular/cellular mechanisms of drugs available in topical formulations utilized in clinical practice and their effectiveness in clinical studies in patients with peripheral neuropathic pain. We searched PubMed for papers published from 1 January 1995 to 30 November 2020. The key search phrases for identifying potentially relevant articles were "topical AND pain", "topical AND neuropathic", "topical AND treatment", "topical AND mechanism", "peripheral neuropathic", and "mechanism". The result of our search was 23 randomized controlled trials (RCT), 9 open-label studies, 16 retrospective studies, 20 case (series) reports, 8 systematic reviews, 66 narrative reviews, and 140 experimental studies. The data from preclinical studies revealed that active compounds of topical treatments exert multiple mechanisms of action, directly or indirectly modulating ion channels, receptors, proteins, and enzymes expressed by neuronal and non-neuronal cells, and thus contributing to antinociception. However, which mechanisms and the extent to which the mechanisms contribute to pain relief observed in humans remain unclear. The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series. For topical ketamine and baclofen, data supporting their effectiveness are provided by both single RCTs and case series. The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy.
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Capsaicin 8% patch Qutenza and other current treatments for neuropathic pain in chemotherapy-induced peripheral neuropathy (CIPN). Curr Opin Support Palliat Care 2021; 15:125-131. [PMID: 33905384 DOI: 10.1097/spc.0000000000000545] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE OF REVIEW Current oral treatments for neuropathic pain associated with chemotherapy-induced peripheral neuropathy (CIPN) have limited clinical efficacy, and undesirable side-effects. Topically delivered treatments have the advantage of avoiding CNS side-effects, while relieving pain. We have reviewed treatments of neuropathic pain associated with CIPN, focusing on the Capsaicin 8% patch, which can provide pain relief for up to 3 months or longer after a single 30-60-min application. RECENT FINDINGS Capsaicin 8% patch is a licensed treatment in the EU/UK for neuropathic pain and shown to be safe and effective in providing pain relief for patients with CIPN. Repeated daily oral or topical administrations are not required, as with other current treatments. The side-effects are transient and restricted to the time around patch application. New evidence suggests the Capsaicin 8% patch can promote the regeneration and restoration of skin nerve fibres in CIPN, in addition to the pain relief. SUMMARY The Capsaicin 8% patch is now often a preferred a treatment option for localised neuropathic pain conditions, including the feet and hands in patients with CIPN. Capsaicin 8% patch can be repeated three-monthly, if needed, for a year. In addition to pain relief, it may have a disease-modifying effect.
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Wang Z, Sun Y, Liu B, Fan Z, Tian J, Lu T. External therapy of Chinese medicine for postherpetic neuralgia: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e23270. [PMID: 33327248 PMCID: PMC7738126 DOI: 10.1097/md.0000000000023270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 10/22/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Postherpetic neuralgia (PHN), the most common complication of herpes zoster, brings about a health-care burden at both the individual and societal levels. External therapy of Chinese medicine (ETCM) is an effective treatment of PHN generally available in China, yet there is incomplete evidence to evaluate the efficacy and safety of it. METHODS This protocol is based on the previous reporting items. We will search 3 English databases (PubMed, EMBASE, and the Cochrane Library) and 3 Chinese databases (CNKI, CBM, and Wan Fang Database) until January 2020. RCTs to evaluate the efficacy and safety of external therapy of Chinese medicine for postherpetic neuralgia will be included. The primary outcome will be assessed by VAS or NRS. We will use the criteria provided by Cochrane Handbook 5.3.0 for quality evaluation and risk assessment, and use the Revman 5.3 software for meta-analysis. ETHICS AND DISSEMINATION Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER CRD42020163511.
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Affiliation(s)
- Zheyi Wang
- Beijing University of Chinese Medicine
- School of Life Science
- Dongzhimen Hospital, Beijing University of Chinese Medicine
| | - Yize Sun
- Beijing University of Chinese Medicine
| | | | - Zhu Fan
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jinzhou Tian
- Dongzhimen Hospital, Beijing University of Chinese Medicine
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Gudin J, Argoff C, Fudin J, Greuber E, Vought K, Patel K, Nalamachu S. A Randomized, Open-Label, Bioequivalence Study of Lidocaine Topical System 1.8% and Lidocaine Patch 5% in Healthy Subjects. Postgrad Med 2020. [PMID: 32606914 DOI: 10.1080/00325481.2018.1512253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Purpose This study was designed to characterize drug delivery with lidocaine topical system 1.8% vs lidocaine patch 5% through 2 PK studies. Patients and Methods Two Phase 1, single-center, open-label, randomized PK studies were performed in healthy adults. In Study 1, 56 subjects received a single intravenous bolus of 0.7 mg/kg of lidocaine as a lead-in to allow for the accurate determination of apparent dose of both products. After a 7-day washout period, subjects were randomized to receive either lidocaine topical system 1.8% or lidocaine patch 5% for 12 hours followed by another 7-day washout period, after which subjects crossed over to receive the other treatment for 12 hours. In Study 2, 54 subjects were randomized to receive either lidocaine topical system 1.8% or lidocaine patch 5% for 12 hours. After a 7-day washout period, subjects crossed over to receive the other treatment. Adhesion and skin irritation assessments were performed after application of the products in Study 2. In both studies, serial blood samples were collected to measure the plasma concentration of lidocaine after product application. Safety assessments and adverse events were monitored in both studies. Results The comparative PK analysis demonstrated that the two products, despite their difference in drug load and strength, are bioequivalent. Both products were well tolerated. In Study 2, dermal response scores (skin tolerability after removal) were similar between lidocaine topical system 1.8% and lidocaine patch 5%, with a mean irritation score per patch <1 (barely perceptible erythema), which is not considered to be clinically significant. Conclusion Bioequivalence was demonstrated between lidocaine topical system 1.8% and lidocaine patch 5%. A comparison of the single-time adhesion scores at 12 hours in Study 2 favored lidocaine topical system 1.8% over lidocaine patch 5%. Both products were well tolerated as a single application in healthy adult human subjects. ClinicalTrialsgov NCT04144192, NCT04149938.
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Affiliation(s)
- Jeffrey Gudin
- Department of Anesthesiology, Englewood Hospital and Medical Center, Englewood, NJ, USA
| | - Charles Argoff
- Department of Neurology, Albany Medical Center, Albany, NY, USA
| | - Jeffrey Fudin
- Professional Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA
| | | | - Kip Vought
- Scilex Pharmaceuticals Inc., Palo Alto, CA, USA
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Gudin J, Argoff C, Fudin J, Greuber E, Vought K, Patel K, Nalamachu S. A Randomized, Open-Label, Bioequivalence Study of Lidocaine Topical System 1.8% and Lidocaine Patch 5% in Healthy Subjects. J Pain Res 2020; 13:1485-1496. [PMID: 32606914 PMCID: PMC7319520 DOI: 10.2147/jpr.s237934] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Accepted: 03/07/2020] [Indexed: 11/30/2022] Open
Abstract
Purpose This study was designed to characterize drug delivery with lidocaine topical system 1.8% vs lidocaine patch 5% through 2 PK studies. Patients and Methods Two Phase 1, single-center, open-label, randomized PK studies were performed in healthy adults. In Study 1, 56 subjects received a single intravenous bolus of 0.7 mg/kg of lidocaine as a lead-in to allow for the accurate determination of apparent dose of both products. After a 7-day washout period, subjects were randomized to receive either lidocaine topical system 1.8% or lidocaine patch 5% for 12 hours followed by another 7-day washout period, after which subjects crossed over to receive the other treatment for 12 hours. In Study 2, 54 subjects were randomized to receive either lidocaine topical system 1.8% or lidocaine patch 5% for 12 hours. After a 7-day washout period, subjects crossed over to receive the other treatment. Adhesion and skin irritation assessments were performed after application of the products in Study 2. In both studies, serial blood samples were collected to measure the plasma concentration of lidocaine after product application. Safety assessments and adverse events were monitored in both studies. Results The comparative PK analysis demonstrated that the two products, despite their difference in drug load and strength, are bioequivalent. Both products were well tolerated. In Study 2, dermal response scores (skin tolerability after removal) were similar between lidocaine topical system 1.8% and lidocaine patch 5%, with a mean irritation score per patch <1 (barely perceptible erythema), which is not considered to be clinically significant. Conclusion Bioequivalence was demonstrated between lidocaine topical system 1.8% and lidocaine patch 5%. A comparison of the single-time adhesion scores at 12 hours in Study 2 favored lidocaine topical system 1.8% over lidocaine patch 5%. Both products were well tolerated as a single application in healthy adult human subjects. ClinicalTrials.gov NCT04144192, NCT04149938. ![]()
Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/OsTX66XQcm0
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Affiliation(s)
- Jeffrey Gudin
- Department of Anesthesiology, Englewood Hospital and Medical Center, Englewood, NJ, USA
| | - Charles Argoff
- Department of Neurology, Albany Medical Center, Albany, NY, USA
| | - Jeffrey Fudin
- Professional Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA
| | | | - Kip Vought
- Scilex Pharmaceuticals Inc., Palo Alto, CA, USA
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Matteo C, Dovrtelova G, Di Clemente A, Frapolli R, Passoni A, Ceruti T, Marsella G, Cervo L, Zucchetti M. HPLC-MS/MS measurement of lidocaine in rat skin and plasma. Application to study the release from medicated plaster. J Chromatogr B Analyt Technol Biomed Life Sci 2020; 1138:121942. [PMID: 31918305 DOI: 10.1016/j.jchromb.2019.121942] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 10/18/2019] [Accepted: 12/16/2019] [Indexed: 11/17/2022]
Abstract
A simple, sensitive HPLC-MS/MS method was developed and validated for the determination of lidocaine in skin and plasma of rats. The methods were established and validated assessing lower limit of quantitation (LLOQ), linearity, intra and inter-day precision and accuracy, selectivity, recovery and matrix effect. Chromatography was done on a Gemini column embedded with C18 stationary phase (50 mm × 2.0 mm, 5 µm particle size), using a gradient with mobile phases consisting of 0.1% HCOOH in bidistilled water and 0.1% HCOOH in acetonitrile. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring, using target ions m/z 235.10 for lidocaine and m/z 245.10 for lidocaine-d10, used as internal standard. RESULTS: The linearity of the method was in the ranges of lidocaine concentrations 10.0-200.0 ng/mL for skin homogenate (accuracy 94.1-105.5%; R2 ≥ 0.998) and 0.025-2 ng/mL for plasma (accuracy 96.2-104.8%; R2 ≥ 0.996). The intra- and inter-day precision and accuracy determined on three quality control samples (20, 75 and 170 ng/mL for skin and 0.075, 0.4 and 1.5 ng/mL for plasma) were ≤4.2% and 103.8-108.2% for skin and ≤12.4% and 95.5-101.4% for plasma. The LLOQ was 10 ng/mL in skin homogenate and 0.025 ng/mL in plasma. The applicability of the method was demonstrated by measuring lidocaine in skin and plasma after exposure to medicated patches containing 5% lidocaine.
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Affiliation(s)
- C Matteo
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - G Dovrtelova
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Department of Pharmacology, Faculty of Medicine, RECETOX Centre, Faculty of Science, Masaryk University and International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic
| | - A Di Clemente
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - R Frapolli
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - A Passoni
- Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - T Ceruti
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - G Marsella
- Animal Care Unit, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - L Cervo
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - M Zucchetti
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
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[Long-term effectiveness of topical analgesics]. Schmerz 2019; 34:21-32. [PMID: 31562537 DOI: 10.1007/s00482-019-00416-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND Neuropathic pain consistently presents a significant therapeutic challenge. Topically applied analgesics have the advantage of showing low systemic side effects, but data on long-term effectiveness are lacking. Consequently, interviews were carried out with all patients being treated with topical analgesics in hospital. METHODS Ethics 16-5690, German Clinical Trials Register (DRKS) 00011877. Between 2008 and 2017 a total of 265 patients were treated at least once with either capsaicin 8% (C), lidocaine 5% (L) and/or perineural botulinum toxin type A (B). From this sample, 205 patients (77%) were interviewed by telephone for feedback on pain reduction (first/last treatment: low/moderate/very good), the possible reduction of analgesic prescription and if applicable the reasons for discontinuation of use (time of interview C: 26 ± 19 months, L: 61 ± 23 months, B: 11 ± 6 months after start). Further pretreatment data and diagnoses were obtained from the in-house documentation system. Responders or long-term responders were defined as patients with at least one moderate pain reduction after the first or last treatment, as long as the effect was adequately maintained. RESULTS In all treatment groups (56 ± 13 years, 62% male, C: 80, L: 84, B: 58 patients) patients with a long history of pain (C: 60 ± 73 months, L: 59 ± 66 months, B: 67 ± 71 months) and high pain intensity (numeric rating scale, NRS, C: 7 ± 2, L: 7 ± 2, B: 6 ± 2), were predominant. The highest primary and long-term responder rates were exhibited by L (57%/60%, B: 52%/37%, C: 23%/15%). With B, long-term responders were most frequently able to reduce analgesic use (74%, C: 58%, L: 38%). DISCUSSION Despite the long duration of the disease, the most used off-label topical drugs L and B demonstrated a high primary response rate (in contrast to C), with most benefiting from long-term treatment.
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Evaluation of the Population Pharmacokinetic Properties of Lidocaine and its Metabolites After Long-Term Multiple Applications of a Lidocaine Plaster in Post-Herpetic Neuralgia Patients. Eur J Drug Metab Pharmacokinet 2018; 42:801-814. [PMID: 28078530 PMCID: PMC5597703 DOI: 10.1007/s13318-017-0400-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Background and Objectives Lidocaine 5% medicated plaster is the first lidocaine containing product for chronic use. As no previous investigations have been conducted to evaluate the population pharmacokinetics of long-term exposure to lidocaine 5% medicated plasters, further insights into the evaluation of the pharmacokinetic properties of lidocaine and its metabolites were needed for the assessment of its safety. Methods The population pharmacokinetic properties of lidocaine and its metabolites were evaluated after multiple applications of lidocaine 5% medicated plasters based on data collected for up to 14.5 months from two phase III clinical trials (up to 2.5 months in the first trial, and up to 12 months in a follow-up trial) in post-herpetic neuralgia patients. Modeling was performed using nonlinear mixed effects as implemented in NONMEM® (nonlinear mixed-effect modeling) v.5. A stepwise forward inclusion and backward elimination procedure were used for covariate model building. Results The model provides reliable estimates of the pharmacokinetic behavior of lidocaine after medicated plaster application. It was validated using simulations and showed adequate predictive properties. Apparent Clearance was estimated to be 48 L/h after application of two or fewer plasters, whereas its value increased to 67 L/h after application of three plasters. Model-based simulations predicted no accumulation of lidocaine or any of its metabolites after long-term exposure of three simultaneous plasters up to 1 year. The variability explained by adding covariates into the model for the long-term exposures of lidocaine following one plaster or three simultaneous plaster applications was found to be very small with respect to the overall between-subject variability. Conclusions In conclusion, exposure to lidocaine after the application of the lidocaine medicated plaster was found to be primarily affected by the number of plasters simultaneously applied, i.e., it increased with the number of applied patches, but less than proportionally. No clinically relevant effect of other covariates was found to affect the exposure to lidocaine or its metabolites. As no accumulation was predicted by the model, long-term exposure to lidocaine and its metabolites is not expected to lead to any safety concerns in post-herpetic neuralgia patients.
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Martini A, Del Balzo G, Schweiger V, Zanzotti M, Picelli A, Parolini M, Chinellato E, Tamburin S, Polati E. Efficacy of lidocaine 5% medicated plaster (VERSATIS®) in patients with localized neuropathic pain poorly responsive to pharmacological therapy. Minerva Med 2018; 109:344-351. [PMID: 29856191 DOI: 10.23736/s0026-4806.18.05690-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Localized neuropathic pain (LNP) is a subgroup of neuropathic pain characterized by consistent and circumscribed area(s) of maximum pain, associated with negative or positive sensory signs and/or spontaneous symptoms characteristic of NP. Lidocaine medicated plasters (LMP) have shown to be effective in pain relief in selective LNP syndromes. METHODS We collected data of 130 patients in our database with LNP syndromes who used LMP. RESULTS Forty-one patients out of 130 patients (32%) were treated with antiepileptics, antidepressants and opioids without improvement and/or with intolerable adverse effects and are not assuming systemic therapy anymore. Globally, during the 12 months follow-up, 15% of patients reached a complete pain relief without any systemic therapy, mainly in trigeminal and post-herpetic neuralgia (P=0.009), 38% of patients reduced analgesic drug consumption with the highest reduction in radiculopathy, post-herpetic neuralgia and trigeminal neuralgia. Topical and transient adverse effects, such as itching or local erythema, were seen in 19/130 (14.6%) patients; 7 of these patients (5.4%) needed to discontinue the treatment due to the occurrence of adverse effects. The dropout rate on global population (excluding cured and lost to follow-up) was 45%, and the main cause of dropouts was the inefficacy of treatment in the first 3 months of therapy with LMP. CONCLUSIONS LMP treatment is safe and worth consideration also as add-on therapy in order to reduce analgesic drug consumption in selected LNP.
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Affiliation(s)
- Alvise Martini
- Department of Surgery, Dentistry, Maternal and Infant Sciences, Pain Therapy Center, Verona University Hospital, Policlinico GB Rossi, Verona, Italy -
| | - Giovanna Del Balzo
- Section of Forensic Medicine, Department of Medicine and Public Health, Verona University Hospital, Policlinico GB Rossi, Verona, Italy
| | - Vittorio Schweiger
- Department of Surgery, Dentistry, Maternal and Infant Sciences, Pain Therapy Center, Verona University Hospital, Policlinico GB Rossi, Verona, Italy
| | - Michele Zanzotti
- Department of Surgery, Dentistry, Maternal and Infant Sciences, Pain Therapy Center, Verona University Hospital, Policlinico GB Rossi, Verona, Italy
| | - Alessandro Picelli
- Department of Neurosciences, Biomedicine and Movement Sciences, Neuromotor and Cognitive Rehabilitation Research Center, Verona University Hospital, Policlinico GB Rossi, Verona, Italy
| | - Massimo Parolini
- Department of Surgery, Dentistry, Maternal and Infant Sciences, Pain Therapy Center, Verona University Hospital, Policlinico GB Rossi, Verona, Italy
| | - Eris Chinellato
- School of Science and Engineering, Middlesex University, London, UK
| | - Stefano Tamburin
- Department of Neurosciences, Biomedicine, and Movement Sciences, Verona University Hospital, Policlinico GB Rossi, Verona, Italy
| | - Enrico Polati
- Department of Surgery, Dentistry, Maternal and Infant Sciences, Pain Therapy Center, Verona University Hospital, Policlinico GB Rossi, Verona, Italy
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Leppert W, Malec-Milewska M, Zajaczkowska R, Wordliczek J. Transdermal and Topical Drug Administration in the Treatment of Pain. Molecules 2018; 23:molecules23030681. [PMID: 29562618 PMCID: PMC6017304 DOI: 10.3390/molecules23030681] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/12/2018] [Accepted: 03/13/2018] [Indexed: 12/21/2022] Open
Abstract
The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients' age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non-steroidal anti-inflammatory drugs (NSAIDs) applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti-inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline) act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.
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Affiliation(s)
- Wojciech Leppert
- Department of Palliative Medicine, Poznan University of Medical Sciences, Osiedle Rusa 55, 61-645 Poznan, Poland.
| | - Malgorzata Malec-Milewska
- Department of Anesthesiology and Intensive Care, Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland.
| | - Renata Zajaczkowska
- Department of Interdisciplinary Intensive Care, Jagiellonian University Medical College, 31-008 Krakow, Poland.
- Department of Anesthesiology and Intensive Therapy, University Hospital, 31-501 Krakow, Poland.
| | - Jerzy Wordliczek
- Department of Interdisciplinary Intensive Care, Jagiellonian University Medical College, 31-008 Krakow, Poland.
- Department of Anesthesiology and Intensive Therapy, University Hospital, 31-501 Krakow, Poland.
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Rousseau V, Morelle M, Arriuberge C, Darnis S, Chabaud S, Launay V, Thouvenin S, Roumenoff-Turcant F, Metzger S, Tourniaire B, Marec-Berard P. Efficacy and Tolerance of Lidocaine 5% Patches in Neuropathic Pain and Pain Related to Vaso-occlusive Sickle Cell Crises in Children: A Prospective Multicenter Clinical Study. Pain Pract 2018; 18:788-797. [DOI: 10.1111/papr.12674] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 12/11/2017] [Accepted: 12/14/2017] [Indexed: 01/20/2023]
Affiliation(s)
- Vanessa Rousseau
- Emergency Department and Pediatric Resuscitation; Civil Hospitals of Lyon; Mother-Child Hospital; Bron France
- Léon Bérard Center; Institute of Hematology and Pediatric Oncology; Lyon France
| | - Magali Morelle
- Léon Bérard Center; Department of Clinical Research and Innovation; Lyon France
- GATE (Analysis and Economic Theory Group); UMR5824; Lyon University; Lyon France
| | - Céline Arriuberge
- Pediatric Analgesia Unit; Trousseau University Hospital Center; Paris France
| | - Sophie Darnis
- Léon Bérard Center; Department of Clinical Research and Innovation; Lyon France
| | - Sylvie Chabaud
- Léon Bérard Center; Department of Clinical Research and Innovation; Lyon France
| | - Valérie Launay
- Emergency Department and Pediatric Resuscitation; Civil Hospitals of Lyon; Mother-Child Hospital; Bron France
| | - Sandrine Thouvenin
- Department of Hematology and Pediatric Oncology; University Hospital Center; Saint-Etienne France
| | | | - Séverine Metzger
- Léon Bérard Center; Department of Clinical Research and Innovation; Lyon France
| | - Barbara Tourniaire
- Pediatric Analgesia Unit; Trousseau University Hospital Center; Paris France
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Knezevic NN, Tverdohleb T, Nikibin F, Knezevic I, Candido KD. Management of chronic neuropathic pain with single and compounded topical analgesics. Pain Manag 2017; 7:537-558. [PMID: 29125423 DOI: 10.2217/pmt-2017-0020] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The goal of our review was to emphasize important aspects that physicians should take into consideration when prescribing topical analgesics as part of chronic neuropathic pain treatment. We discuss the dermatopharmacokinetics and microstructural components of the skin, differences between topical and transdermal drug delivery, and topical medication effects on peripheral neuropathy and central sensitization. Even though the US FDA approved topical analgesics are 8%-capsaicin and 5%-lidocaine patches for treating postherpetic neuralgia, there are many other studies conducted on the efficacy of topical ketamine cream, clonidine gel, topical gabapentin, topical baclofen and topical phenytoin for peripheral neuropathic pain, either alone or in combination with other formulations. Furthermore, we discuss new compounded topical analgesics that are becoming more popular and that are showing promising results in the management of chronic peripheral neuropathies. However, more studies are needed for elucidation of the role of topical analgesics and their effects, especially when combined with other treatments.
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Affiliation(s)
- Nebojsa Nick Knezevic
- Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA.,Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA.,Department of Surgery, University of Illinois, Chicago, IL 60612, USA
| | - Tatiana Tverdohleb
- Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA
| | - Farid Nikibin
- Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA
| | - Ivana Knezevic
- Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA
| | - Kenneth D Candido
- Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA.,Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA.,Department of Surgery, University of Illinois, Chicago, IL 60612, USA
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Sabatowski R, Bösl I, König S, Buchheister B, Meier T, Baron R. Treatment of postherpetic neuralgia with 5% lidocaine medicated plaster in elderly patients - subgroup analyses from three European clinical trials. Curr Med Res Opin 2017; 33:595-603. [PMID: 28035844 DOI: 10.1080/03007995.2016.1277990] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
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.
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Affiliation(s)
- Rainer Sabatowski
- a Comprehensive Pain Center, University Hospital Carl Gustav Carus Dresden , Dresden , Germany
| | - Irmgard Bösl
- b Grünenthal Global Innovations/Clinical Development , Aachen , Germany
| | - Simone König
- b Grünenthal Global Innovations/Clinical Development , Aachen , Germany
| | | | - Torsten Meier
- d Brüderkrankenhaus St. Josef Paderborn , Paderborn , Germany
| | - Ralf Baron
- e Division of Neurological Pain Research and Therapy, Department of Neurology , University Hospital of Schleswig-Holstein , Kiel Campus , Kiel , Germany
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Abstract
Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. This article is about postherpetic neuralgia (PHN), a devastating complication following reactivation of the varicella-zoster virus. The answer offers an explanation for why this pain occurs, and cites literature regarding its incidence and treatment.
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Binder A, Rogers P, Hans G, Baron R. Impact of topical 5% lidocaine-medicated plasters on sleep and quality of life in patients with postherpetic neuralgia. Pain Manag 2016; 6:229-39. [DOI: 10.2217/pmt-2015-0010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To determine the impact of 5% lidocaine-medicated plasters on sleep, quality of life and pain in 265 patients with postherpetic neuralgia (PHN). Patients & methods: An 8-week, open-label arm of a double-blind controlled withdrawal study. Results: Patients treated with 5% lidocaine had less trouble falling asleep, used less sleep medication, had fewer awakenings due to pain at night or in the morning and their perception of quality of life was improved. The 15 pain descriptors in the Short-Form McGill Pain Questionnaire were improved from baseline to week 8, with a decrease in the proportion of patients reporting ‘severe’ pain and an increase in the number reporting ‘none/mild’ pain. Conclusion: 5% lidocaine-medicated plasters provide benefits beyond pain relief for patients with postherpetic neuralgia.
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Affiliation(s)
- Andreas Binder
- Division of Neurological Pain Research & Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Peter Rogers
- Department of Pain Medicine, St Mary's Hospital, Portsmouth, UK
| | - Guy Hans
- Multidisciplinary Pain Center (PCT), Antwerp University Hospital (UZA), Edegem, Belgium
| | - Ralf Baron
- Division of Neurological Pain Research & Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
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de León-Casasola OA, Mayoral V. The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence. J Pain Res 2016; 9:67-79. [PMID: 26929664 PMCID: PMC4758786 DOI: 10.2147/jpr.s99231] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP). This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series). The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (≤7 years) use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug–drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events.
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Affiliation(s)
- Oscar A de León-Casasola
- Department of Anesthesiology, Division of Pain Medicine, Roswell Park Cancer Institute, NY, USA; University at Buffalo, School of Medicine and Biomedical Sciences. NY, USA
| | - Victor Mayoral
- Anesthesiology Department, Pain Management Unit, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Spain
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Niederberger E, Kuner R, Geißlinger G. [Pharmacological aspects of pain research in Germany]. Schmerz 2015; 29:531-8. [PMID: 26294077 DOI: 10.1007/s00482-015-0042-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
In spite of several approved analgesics, the therapy of pain still constitutes a challenge due to the fact that the drugs do not exert sufficient efficacy or are associated with severe side effects. Therefore, the development of new and improved painkillers is still of great importance. A number of highly qualified scientists in Germany are investigating signal transduction pathways in pain, effectivity of new drugs and the so far incompletely investigated mechanisms of well-known analgesics in preclinical and clinical studies. The highlights of pharmacological pain research in Germany are summarized in this article.
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Affiliation(s)
- E Niederberger
- pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Deutschland
| | - R Kuner
- Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 584, 69120, Heidelberg, Deutschland
| | - G Geißlinger
- pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Deutschland.
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Navez ML, Monella C, Bösl I, Sommer D, Delorme C. 5% Lidocaine Medicated Plaster for the Treatment of Postherpetic Neuralgia: A Review of the Clinical Safety and Tolerability. Pain Ther 2015; 4:1-15. [PMID: 25896574 PMCID: PMC4470968 DOI: 10.1007/s40122-015-0034-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Indexed: 12/23/2022] Open
Abstract
Postherpetic neuralgia (PHN) is a common, very painful, and often long-lasting complication of herpes zoster which is frequently underdiagnosed and undertreated. It mainly affects the elderly, many of whom are already treated for comorbidities with a variety of systemic medications and are thus at high risk of drug-drug interactions. An efficacious and safe treatment with a low interaction potential is therefore of high importance. This review focuses on the safety and tolerability of the 5% lidocaine medicated plaster, a topical analgesic indicated for the treatment of PHN. The available literature (up to June 2014) was searched for publications containing safety data regarding the use of the 5% lidocaine medicated plaster in PHN treatment; unpublished clinical safety data were also included in this review. The 5% lidocaine medicated plaster demonstrated good short- and long-term tolerability with low systemic uptake (3 ± 2%) and minimal risk for systemic adverse drug reactions (ADRs). ADRs related to topical lidocaine treatment were mainly application site reactions of mild to moderate intensity. The treatment discontinuation rate was generally below 5% of patients. In one trial, the 5% lidocaine medicated plaster was better tolerated than systemic treatment with pregabalin. The 5% lidocaine medicated plaster provides a safe alternative to systemic medications for PHN treatment, including long-term pain treatment.
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Affiliation(s)
- Marie Louise Navez
- Center for Pain Evaluation and Treatment, Saint Etienne Hospital, Saint Etienne, France,
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Paster Z, Morris CM. Treatment of the Localized Pain of Postherpetic Neuralgia. Postgrad Med 2015; 122:91-107. [DOI: 10.3810/pgm.2010.01.2103] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Khot S, Morgan CL, Kadambande S, Poole CD. Use of 5% lidocaine medicated plasters for the treatment of pain in routine hospital practice: patient reported pain, functioning and satisfaction. Curr Med Res Opin 2014; 30:1573-8. [PMID: 24773481 DOI: 10.1185/03007995.2014.915212] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE 5% lidocaine medicated plasters are a topical option in the treatment of peripheral neuropathic pain, as monotherapy or as an adjunct to systemic medication. This study sought to determine the impact of lidocaine plaster use on self-reported pain, functioning and patient satisfaction within a large teaching hospital. RESEARCH DESIGN AND METHODS Patients were selected from the pain and rheumatology outpatient departments in Cardiff, Wales (2008-9). Postal surveys were sent to patients prescribed lidocaine plaster asking whether patients currently used the plaster and, if not, reason for discontinuation. Patients were asked to record pain score before and after therapy initiation, percentage pain relief, duration of effectiveness and impact on functioning. MAIN OUTCOME MEASURES Pain scores, pain relief and levels of functioning before and after treatment. RESULTS A total of 850 surveys were dispatched; 408 (48.0%) responses received; 197 (48.3%) patients were current users at survey completion. Median pain score prior to plaster use was 8 (IQR 7-9). One month after initiation, median pain score was 6 (4-8, p < 0.001) overall and 5 (4-7, p < 0.001) for current users. Median pain relief, after initial month of plaster use, was 30% (10-60%) for all patients and 50% (30-70%) for current users, whilst pain relief at time of survey was 30% (0-60%) and 50% (30-70%), respectively. A total of 181 (93.3%) current users claimed the plasters were effective. All three measures of functioning were significantly improved in current users: sleep (63.3% versus 20.1%, p < 0.001), mood (59.2% versus 18.6%, p < 0.001) and activity level (50.0% versus 19.5%, p < 0.001). Median satisfaction was 5 (IQR 1-8) for all patients and 7 (5-9) for current plaster users. CONCLUSIONS The results of this study need to be considered within the context of a self-reported survey. However, pain, functioning and patient satisfaction were significantly improved in current users of 5% lidocaine medicated plasters.
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Affiliation(s)
- S Khot
- Department of Anaesthesia, Intensive Care and Pain Medicine, University Hospital of Wales , Cardiff , UK
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Diagnosis and management of neuropathic pain: Review of literature and recommendations of the Polish Association for the Study of Pain and the Polish Neurological Society – Part one. Neurol Neurochir Pol 2014; 48:262-71. [DOI: 10.1016/j.pjnns.2014.07.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Revised: 07/23/2014] [Accepted: 07/24/2014] [Indexed: 11/18/2022]
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Casale R, Di Matteo M, Minella CE, Fanelli G, Allegri M. Reduction of painful area as new possible therapeutic target in post-herpetic neuropathic pain treated with 5% lidocaine medicated plaster: a case series. J Pain Res 2014; 7:353-7. [PMID: 25018649 PMCID: PMC4075948 DOI: 10.2147/jpr.s65398] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Post-herpetic neuralgia (PHN) is neuropathic pain persisting after an acute episode of herpes zoster, and is associated with severe pain and sensory abnormalities that adversely affect the patient's quality of life and increase health care costs. Up to 83% of patients with PHN describe localized neuropathic pain, defined as "a type of neuropathic pain characterized by consistent and circumscribed area(s) of maximum pain". Topical treatments have been suggested as a first-line treatment for localized neuropathic pain. Use of 5% lidocaine medicated plaster could reduce abnormal nervous peripheral discharge and via the plaster could have a "protective" function in the affected area. It has been suggested that use of this plaster could reduce pain as well as the size of the painful area. To evaluate this possible outcome, we retrospectively reviewed eight patients with PHN, treated using 5% lidocaine medicated plaster. During a follow-up period of 3 months, we observed good pain relief, which was associated with a 46% reduction in size of the painful area after one month (from 236.38±140.34 cm(2) to 128.80±95.7 cm(2)) and a 66% reduction after 3 months (81.38±59.19 cm(2)). Our study cohort was composed mainly of elderly patients taking multiple drugs to treat comorbidities, who have a high risk of drug-drug interactions. Such patients benefit greatly from topical treatment of PHN. Our observations confirm the effectiveness of lidocaine plasters in the treatment of PHN, indicating that 5% lidocaine medicated plaster could reduce the size of the painful area. This last observation has to be confirmed and the mechanisms clarified in appropriate larger randomized controlled trials.
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Affiliation(s)
- Roberto Casale
- Department of Clinical Neurophysiology and Pain Rehabilitation Unit, Foundation Salvatore Maugeri, IRCCS, Pavia, Italy ; EFIC Montescano School, Montescano, Italy
| | - Maria Di Matteo
- Anesthesia and Intensive Care I, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy ; Study In Multidisciplinary Pain Research Group, Parma, Italy
| | - Cristina E Minella
- Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy ; Study In Multidisciplinary Pain Research Group, Parma, Italy
| | - Guido Fanelli
- Department of Anesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, Italy ; Study In Multidisciplinary Pain Research Group, Parma, Italy
| | - Massimo Allegri
- Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy ; Department of Clinical, Surgical, Diagnostic and Pediatric Science, University of Pavia, Pavia, Italy ; Study In Multidisciplinary Pain Research Group, Parma, Italy
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Liedgens H, Obradovic M, Nuijten M. Health economic evidence of 5% lidocaine medicated plaster in post-herpetic neuralgia. CLINICOECONOMICS AND OUTCOMES RESEARCH 2013; 5:597-609. [PMID: 24348056 PMCID: PMC3848379 DOI: 10.2147/ceor.s51776] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Post-herpetic neuralgia (PHN) is the most common and most debilitating complication of herpes zoster, and involves considerable associated costs. OBJECTIVE This paper presents results from nine health economic studies undertaken in eight European countries that compared lidocaine medicated plaster with gabapentin and/or pregabalin in PHN. It aims to support the increasing need for published cost-effectiveness data for health care decision-making processes in Europe. METHODS All studies were based on a similar core Markov model with data derived from clinical trials, local Delphi panels, and official national price and tariff lists. The main outcome measure was cost per quality-adjusted life year gained; time without pain or intolerable adverse events was also included as a secondary outcome measure. All studies focused on an elderly population of patients with PHN who had insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants. RESULTS Despite considerable differences in many of the variables used, the results showed remarkable similarity and suggested that use of lidocaine medicated plaster offered cost-savings in many of the countries studied, where it proved a highly cost-effective alternative to both gabapentin and pregabalin. CONCLUSION Lidocaine medicated plaster is a cost-effective alternative to gabapentin and pregabalin in the treatment of PHN. These savings are largely the result of the superior safety profile of the lidocaine medicated plaster.
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Lidocaine 5 % patches as an effective short-term co-analgesic in cancer pain. Preliminary results. Support Care Cancer 2013; 21:3153-8. [PMID: 24000041 DOI: 10.1007/s00520-013-1948-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2012] [Accepted: 08/13/2013] [Indexed: 10/26/2022]
Abstract
PURPOSE To analyze the short-term efficacy and patients' subjective perception of the use of lidocaine 5 % patches for painful scars (post-thoracotomy and post-mastectomy) and pain caused by chest wall tumors. METHODS This is a prospective, descriptive, non-controlled, non-randomized, open-label study of patients seen in the palliative care outpatient clinic. Demographic data, variables relating to the severity of the pain, and concomitant therapy both at the start and end of treatment, the need for interventional anesthetic techniques (IAT), patients' subjective perception and treatment-related side effects were all recorded. RESULTS Twenty patients were included with a mean follow-up of 29.2 days. The treatment led to a statistically significant clinical improvement in pain severity. There was no clinically significant opioid dose escalation during the treatment period. Only three patients required IAT to relieve the pain. Sixty five percent of patients were very satisfied with the therapy. No systemic or local adverse events were reported. CONCLUSIONS The addition of lidocaine 5 % patches is effective in the short term for the treatment of neuropathic cancer pain accompanied by allodynia, whether deriving from a painful scar or chest wall tumor. These findings need to be confirmed by randomized controlled trials with larger samples.
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Bruckenthal P, Barkin RL. Options for treating postherpetic neuralgia in the medically complicated patient. Ther Clin Risk Manag 2013; 9:329-40. [PMID: 23990726 PMCID: PMC3753169 DOI: 10.2147/tcrm.s47138] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Patients with postherpetic neuralgia (PHN) are often of advanced age or immunocompromised and likely to have ≥1 comorbid medical condition for which they receive ≥1 medication (polypharmacy). Comorbidities affecting renal or hepatic function can alter pharmacokinetics, thereby impacting the efficacy or tolerability of PHN analgesic therapies. Cardiovascular, cerebrovascular, or psychiatric comorbidities may increase patient vulnerability to potential adverse events associated with some PHN analgesic therapies. Because PHN is a localized condition, localized therapy with a topical analgesic (lidocaine patch 5% and capsaicin 8% patch or cream) may provide adequate efficacy while mitigating the risk of systemic adverse events compared with oral analgesics (eg, tricyclic antidepressants, anticonvulsants, opioids). However, combined therapy with a topical and an oral analgesic or with >1 oral analgesic may be needed for optimal pain management in some patients. This review summarizes how comorbidities and concomitant medications should be taken into account when selecting among available pharmacotherapies for PHN and provides recommendations for the selection of therapies that will provide analgesia while minimizing the risk of adverse events.
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Affiliation(s)
- Patricia Bruckenthal
- Department of Graduate Studies in Advanced Practice Nursing, Stony Brook University School of Nursing, Stony Brook, NY, USA
| | - Robert L Barkin
- Department of Anesthesiology, Family Medicine, and Pharmacology, Rush University Medical College, Chicago, IL, USA
- Department of Anesthesiology, Northshore University Health System Pain Centers, Skokie and Evanston Hospitals, Skokie and Evanston, IL, USA
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Abstract
OPINION STATEMENT Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines and virus reactivates to cause zoster (shingles), which can occur anywhere on the body. Skin lesions resolve within 1-2 weeks, while complete cessation of pain usually takes 4-6 weeks. Zoster can be followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, meningoencephalitis, cerebellitis, myelopathy, multiple ocular disorders and vasculopathy that can mimic giant cell arteritis. All of the neurological and ocular disorders listed above may also develop without rash. Diagnosis of VZV-induced neurological disease may require examination of cerebrospinal fluid (CSF), serum and/ or ocular fluids. In the absence of rash in a patient with neurological disease potentially due to VZV, CSF should be examined for VZV DNA by PCR and for anti-VZV IgG and IgM. Detection of VZV IgG antibody in CSF is superior to detection of VZV DNA in CSF to diagnose vasculopathy, recurrent myelopathy, and brainstem encephalitis. Oral antiviral drugs speed healing of rash and shorten acute pain. Immunocompromised patients require intravenous acyclovir. First-line treatments for post-herpetic neuralgia include tricyclic antidepressants, gabapentin, pregabalin, and topical lidocaine patches. VZV vasculopathy, meningoencephalitis, and myelitis are all treated with intravenous acyclovir.
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Affiliation(s)
- Maria A. Nagel
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Don Gilden
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA
- Department of Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
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Khadem T, Stevens V. Therapeutic options for the treatment of postherpetic neuralgia: a systematic review. J Pain Palliat Care Pharmacother 2013; 27:268-83. [PMID: 23901906 DOI: 10.3109/15360288.2013.816408] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Postherpetic neuralgia (PHN) is a chronic and painful condition that may result in significant disturbances to normal activities and decreases in the quality of life for those affected. Despite the availability of several first- and second-line treatment options, many patients may experience refractory pain. The objectives of this review were to summarize evidence for Food and Drug Administration (FDA)-approved and off-label therapies for the treatment of PHN and to present gaps in the current literature for future research focus. Several agents, including pregabalin, gabapentin, and opioids, have been shown to significantly improve pain when compared with placebo. However, evidence regarding the comparative effectiveness of these treatment alternatives is lacking. In order to choose the optimal treatment, providers should consider issues related to efficacy, safety, and tolerability in conjunction with patient goals, preferences, and adherence issues. Evidence from randomized or observational studies that directly compare agents with each other should help to inform treatment choices.
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Affiliation(s)
- Tina Khadem
- Department of Pharmacy Practice, SUNY Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York, USA
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Kern KU, Nalamachu S, Brasseur L, Zakrzewska JM. Can treatment success with 5% lidocaine medicated plaster be predicted in cancer pain with neuropathic components or trigeminal neuropathic pain? J Pain Res 2013; 6:261-80. [PMID: 23630431 PMCID: PMC3623573 DOI: 10.2147/jpr.s39957] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
An expert group of 40 pain specialists from 16 countries performed a first assessment of the value of predictors for treatment success with 5% lidocaine-medicated plaster in the management of cancer pain with neuropathic components and trigeminal neuropathic pain. Results were based on the retrospective analysis of 68 case reports (sent in by participants in the 4 weeks prior to the conference) and the practical experience of the experts. Lidocaine plaster treatment was mostly successful for surgery or chemotherapy-related cancer pain with neuropathic components. A dose reduction of systemic pain treatment was observed in at least 50% of all cancer pain patients using the plaster as adjunct treatment; the presence of allodynia, hyperalgesia or pain quality provided a potential but not definitively clear indication of treatment success. In trigeminal neuropathic pain, continuous pain, severe allodynia, hyperalgesia, or postherpetic neuralgia or trauma as the cause of orofacial neuropathic pain were perceived as potential predictors of treatment success with lidocaine plaster. In conclusion, these findings provide a first assessment of the likelihood of treatment benefits with 5% lidocaine-medicated plaster in the management of cancer pain with neuropathic components and trigeminal neuropathic pain and support conducting large, well-designed multicenter studies.
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Orellana Silva M, Yañez V, Hidalgo G, Valenzuela F, Saavedra R. 5% lidocaine medicated plaster use in children with neuropathic pain from burn sequelae. PAIN MEDICINE 2012; 14:422-9. [PMID: 23279572 DOI: 10.1111/pme.12020] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Neuropathic pain is a challenge in children with burn sequelae. Although relatively infrequent, the intensity and chronicity of neuropathic pain negatively impact functionality and quality of life. The use of 5% lidocaine medicated plaster has not previously been reported in children. We explored the effectiveness and safety of 5% lidocaine medicated plaster to treat neuropathic pain in children with burn sequelae. DESIGN Three-month prospective, uncontrolled study. SETTING Corporation of Aid to Burned Children (COANIQUEM), a nonprofit pediatric burn rehabilitation center in Chile. SUBJECTS Fourteen pediatric patients with burn sequelae neuropathic pain. OUTCOME MEASURES Demographics, burn and pain evolution (type, intensity [using Wong-Baker FACES], and Douleur Neuropathique 4 [DN4]), and patient functionality. Plasma lidocaine levels were measured at 0, 12, 36, and 60 hours after treatment commencement. RESULTS Fourteen patients were evaluable for plasma lidocaine levels. Twelve patients were available for clinical assessment (two patients lost to follow-up) [mean (standard deviation)]: age, 11 years 7 months (2 years 6 months); weight, 45 kg (11.9 kg); burn evolution, 5 years 6 months (4 years); time between burn and pain onset, 3 years 6 months (3 years 2 months); time between pain onset and treatment, 5.1 months (4.8 months); lidocaine, between < and ½ plaster; initial pain intensity (FACES), 6.8 (1.6); final pain intensity, 0 in 11/12 patients; DN4, initial-6, final-2.3. All patients reported improved functionality. Plasma lidocaine levels were ≤27.45 ng/mL (>180 times below critical levels). No adverse reactions occurred. CONCLUSIONS These are the first published data suggesting that 5% lidocaine medicated plaster improves patient functionality, and is effective and safe for the treatment of neuropathic pain in pediatric patients with burn sequelae.
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Affiliation(s)
- Matias Orellana Silva
- Pain Unit, Department of Rehabilitation, COANIQUEM (Corporation of Aid to Burned Children), Santiago, Chile.
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Abstract
Postherpetic neuralgia (PHN) represents a potentially debilitating and often undertreated form of neuropathic pain that disproportionately affects vulnerable populations, including the elderly and the immunocompromised. Varicella zoster infection is almost universally prevalent, making prevention of acute herpes zoster (AHZ) infection and prompt diagnosis and aggressive management of PHN of critical importance. Despite the recent development of a herpes zoster vaccine, prevention of AHZ is not yet widespread or discussed in PHN treatment guidelines. Diagnosis of PHN requires consideration of recognized PHN signs and known risk factors, including advanced age, severe prodromal pain, severe rash, and AHZ location on the trigeminal dermatomes or brachial plexus. PHN pain is typically localized, unilateral and chronic, but may be constant, intermittent, spontaneous and/or evoked. PHN is likely to interfere with sleep and daily activities. First-line therapies for PHN include tricyclic antidepressants, gabapentin and pregabalin, and the lidocaine 5 % patch. Second-line therapies include strong and weak opioids and topical capsaicin cream or 8 % patch. Tricyclic antidepressants, gabapentinoids and strong opioids are effective but are also associated with systemic adverse events that may limit their use in many patients, most notably those with significant medical comorbidities or advanced age. Of the topical therapies, the topical lidocaine 5 % patch has proven more effective than capsaicin cream or 8 % patch and has a more rapid onset of action than the other first-line therapies or capsaicin. Given the low systemic drug exposure, adverse events with topical therapies are generally limited to application-site reactions, which are typically mild and transient with lidocaine 5 % patch, but may involve treatment-limiting discomfort with capsaicin cream or 8 % patch. Based on available clinical data, clinicians should consider administering the herpes zoster vaccine to all patients aged 60 years and older. Clinicians treating patients with PHN may consider a trial of lidocaine 5 % patch monotherapy before resorting to a systemic therapy, or alternatively, may consider administering the lidocaine 5 % patch in combination with a tricyclic antidepressant or a gabapentinoid to provide more rapid analgesic response and lower the dose requirement of systemic therapies.
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Affiliation(s)
- Srinivas Nalamachu
- International Clinical Research Institute, Inc., 8675 College Blvd, Suite 150, Overland Park, KS 66210 USA
| | - Patricia Morley-Forster
- Interdisciplinary Pain Program, University of Western Ontario, St. Josephs Hospital, Room B3-628, 268 Grosvenor Street, London, ON N6A 4V2 Canada
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Tontodonati M, Ursini T, Polilli E, Vadini F, Di Masi F, Volpone D, Parruti G. Post-herpetic neuralgia. Int J Gen Med 2012; 5:861-71. [PMID: 23109810 PMCID: PMC3479946 DOI: 10.2147/ijgm.s10371] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background In spite of the large body of evidence available in the literature, definition and treatment of Post-Herpetic Neuralgia (PHN) are still lacking a consistent and universally recognized standardization. Furthermore, many issues concerning diagnosis, prediction and prevention of PHN need to be clarified in view of recent contributions. Objectives To assess whether PHN may be better defined, predicted, treated and prevented in light of recent data, and whether available alternative or adjunctive therapies may improve pain relief in treatment recalcitrant PHN. Methods Systematic reviews, meta-analyses, randomized controlled trials, cohort studies and protocols were searched; the search sources included PubMed, Cochrane Library, NICE, and DARE. More than 130 papers were selected and evaluated. Results Diagnosis of PHN is essentially clinical, but it can be improved by resorting to the many tools available, including some practical and accessible questionnaires. Prediction of PHN can be now much more accurate, taking into consideration a few well validated clinical and anamnestic variables. Treatment of PHN is presently based on a well characterized array of drugs and drug associations, including, among others, tricyclic antidepressants, gabapentinoids, opioids and many topical formulations. It is still unsatisfactory, however, in a substantial proportion of patients, especially those with many comorbidities and intense pain at herpes zoster (HZ) presentation, so that this frequent complication of HZ still strongly impacts on the quality of life of affected patients. Conclusion Further efforts are needed to improve the management of PHN. Potentially relevant interventions may include early antiviral therapy of acute HZ, prevention of HZ by adult vaccination, as well as new therapeutic approaches for patients experiencing PHN.
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Tarameshloo M, Norouzian M, Zarein-Dolab S, Dadpay M, Mohsenifar J, Gazor R. Aloe vera gel and thyroid hormone cream may improve wound healing in Wistar rats. Anat Cell Biol 2012; 45:170-7. [PMID: 23094205 PMCID: PMC3472143 DOI: 10.5115/acb.2012.45.3.170] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2012] [Revised: 07/25/2012] [Accepted: 08/09/2012] [Indexed: 11/27/2022] Open
Abstract
Therapeutic effects of various treatment options in wound healing have been one of the most controversial issues in surgical science. The present study was carried out to examine and compare the effects of Aloe vera gel, thyroid hormone cream and silver sulfadiazine cream onsutured incisions in Wistar rats. In a randomized controlled trial, thirty-six Wistar male rats, 250 to 300 g, received surgical incisions followed by topical application of Aloe vera gel, thyroid hormone cream and silver sulfadiazine 1%. To assess the efficacy of each treatment technique, a histological approach was used to evaluate the mean number of fibroblasts, macrophages, neutrophils, blood vessel sections and thickness of the regenerating epithelium and dermis on days 4, 7 and 14. Re-epithelialization and angiogenesis were significantly improved in Aloe vera gel group compared with the other treatments while thyroid hormone cream had positive effects on day 4 (P≤0.05). Topical administration of Aloe vera gel is recommended as the treatment of choice for surgical incisions.
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Affiliation(s)
- Mahsa Tarameshloo
- Department of Anatomy and Cell Biology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Sabatowski R, Hans G, Tacken I, Kapanadze S, Buchheister B, Baron R. Safety and efficacy outcomes of long-term treatment up to 4 years with 5% lidocaine medicated plaster in patients with post-herpetic neuralgia. Curr Med Res Opin 2012; 28:1337-46. [PMID: 22769236 DOI: 10.1185/03007995.2012.707977] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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).
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Affiliation(s)
- Rainer Sabatowski
- Comprehensive Pain Center (USC), University Hospital Carl Gustav Carus, Dresden, Germany.
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Abstract
BACKGROUND The topical 5% lidocaine medicated plaster is recommended as first-line treatment for localized peripheral neuropathic pain. SCOPE In order to provide an overview of the efficacy and safety of the lidocaine plaster in the treatment of different neuropathic pain conditions, all efficacy and safety studies (randomized, controlled, or open-label with well described methodology), case reports, and pharmacological studies on the lidocaine plaster retrieved from a PubMed literature research (1960-March 2012) plus additional references identified from retrieved articles were included. FINDINGS The lidocaine plaster is efficacious in the treatment of neuropathic pain symptoms associated with previous herpes zoster infection. Results from a large open-label controlled study suggest that the lidocaine plaster could be at least as effective as systemic pregabalin in the treatment of postherpetic neuralgia and painful diabetic polyneuropathy. Open-label studies indicate efficacy in the treatment of other localized neuropathic pain conditions, such as painful idiopathic sensory polyneuropathy, complex regional pain syndrome, carpal tunnel syndrome sequelae, postsurgical and posttraumatic pain. Quality of life markedly improved in a variety of neuropathic pain conditions and long-term treatment provided sustained relief in patients with neuropathic pain who are responsive to lidocaine plaster. The lidocaine plaster is usually well tolerated. The risk of systemic adverse events and pharmacokinetic interactions with concomitant medication is minimal owing to low systemic exposure. CONCLUSIONS Treatment of several, primarily neuropathic and mixed-pain conditions with the 5% lidocaine medicated plaster was found efficacious and safe. Further controlled studies, in particular where only small open-label studies or case reports are available, should be considered.
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Affiliation(s)
- Gérard Mick
- Center for Pain Evaluation and Treatment, University Neurological Hospital, Lyon, France.
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Überall MA, Müller-Schwefe GHH. Patient perceptions associated with the 5% lidocaine medicated plaster in daily practice. Curr Med Res Opin 2012; 28:901-9. [PMID: 22506624 DOI: 10.1185/03007995.2012.685929] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To evaluate patients' perceptions of 5% lidocaine medicated plaster for treatment of chronic neuropathic pain in daily clinical practice. RESEARCH DESIGN AND METHODS In a prospective, multicentre, non-interventional observation, patient-reported outcome data were collected in clinical practices in Germany using the German Pain Questionnaire for pre-treatment documentation and the German Pain Diary for documentation of weekly treatment-associated changes. Questionnaires were completed by the patients without input from their physicians. MAIN OUTCOME MEASURES Mean changes over the 12-week treatment period in pain intensity, in impairments of daily activities (modified pain disability index, mPDI) and of quality of life (quality of life impairment by pain inventory, QLIP), in Hospital Anxiety and Depression Scale scores (HADS-A and HADS-D), and in overall burden of pain. RESULTS Data of 922 patients were evaluated. Mean average pain intensity over 24 h improved by 5.1 points (74%) from 6.9 ± 1.6 points at baseline. A 30% reduction in overall pain intensity was already observed within the first 2-3 weeks with continuous further reductions until end of observation. Marked improvements in anxiety and depression scores (40% and 52%, respectively), and in pain-related restrictions in daily life activities (66%) and quality of life (157%) were also noted. Burden of pain was reduced by 56.2 points (73%) from 77.5 points at baseline. Stratification by diagnosis showed a treatment effect of lidocaine plaster for all underlying conditions with highest treatment effects for diabetic polyneuropathy and postherpetic neuralgia. CONCLUSIONS In a patient population where 46% of individuals already suffered from chronic to markedly chronic pain, patients perceive the 5% lidocaine medicated plaster as an efficacious topical treatment of chronic neuropathic pain in daily clinical practice. Strongest pain relief as well as associated improvements in pain-related restrictions were observed within the first five treatment weeks; however, beneficial effects continued until end of observation.
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Affiliation(s)
- Michael A Überall
- Institute for Neurological Sciences, Algesiology and Paediatrics, Nürnberg, Germany.
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Clère F, Delorme-Morin C, George B, Navez M, Rioult B, Tiberghien-Chatelain F, Ganry H. 5% lidocaine medicated plaster in elderly patients with postherpetic neuralgia: results of a compassionate use programme in France. Drugs Aging 2012; 28:693-702. [PMID: 21913735 DOI: 10.2165/11595600-000000000-00000] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND Postherpetic neuralgia (PHN) is a common, debilitating complication of herpes zoster that has a major impact on patients' quality of life. PHN prevalence increases with advancing age. One treatment option is the topical analgesic 5% lidocaine (lignocaine) medicated plaster (Versatis®), which has been proven to be efficacious and well tolerated in a number of randomized clinical studies. OBJECTIVE The aim of this analysis was to assess the use of the lidocaine medicated plaster under clinical practice conditions in a patient population whose previous PHN treatment with antidepressant and/or antiepileptic agents was inadequate or was not tolerated, or for whom such treatment was contraindicated or not recommended. METHODS This was a prospective, multicentre, non-interventional observation conducted in private and public health centres in France under a compassionate use programme (CUP). To obtain this new - and, at the time, unauthorized - PHN treatment alternative, physicians (in accordance with French guidelines) had to complete standardized case report forms for each patient before his/her inclusion in the CUP. As it was a CUP and therefore a non-interventional observation, returning documented information on follow-up visits to the medication provider was voluntary, and only a limited number of physicians returned completed forms. Documentation was, however, mandatory for adverse events (AEs) occurrence. Depending on the size of the painful skin area, up to three lidocaine plasters daily were applied for a maximum of 12 hours with plaster-free intervals of at least 12 hours. The study assessed changes in the prescription of concomitant PHN medication from the start of lidocaine plaster treatment to the last follow-up visit, both in terms of the sum of all concomitant PHN treatments and stratified by type of treatment: antiepileptic drugs, tricyclic antidepressants (TCAs), serotonin reuptake inhibitors (SRIs), classical analgesics (classified as step 1, 2 or 3 according to the WHO cancer pain ladder), transcutaneous electrical nerve stimulation, and others (mainly NSAIDs). AEs were monitored for safety. RESULTS A total of 625 patients were included in the CUP and permitted to receive lidocaine plaster treatment. Physicians returned 273 documented follow-up visit report forms. The mean ± SD CUP duration (i.e. duration of lidocaine plaster treatment) was 2.4 ± 2.5 months (median 1 month). Efficacy was assessed in the group of patients with documented follow-up visits (n = 273; mean ± SD age 73.6 ± 11.2 years), of whom 184 were aged ≥70 years (elderly efficacy population). The safety analysis included 625 patients (mean ± SD age 73.2 ± 11.9 years). Lidocaine plaster treatment resulted in a significant mean reduction of one concomitant PHN treatment per patient in the overall efficacy population analysed at the end of the observation (p < 0.001). In both populations (overall efficacy and elderly efficacy population), significantly fewer patients received TCAs (p = 0.003 and p = 0.001, respectively), step 3 analgesics (p = 0.001 and p = 0.005, respectively), and other miscellaneous treatments (p < 0.001 for both populations); there was also a significant reduction in the proportion of patients who took step 2 analgesics (p = 0.009) in the overall efficacy group. AEs (mainly related to local plaster application) were documented for 2.6% of the patients in the safety population; none were considered serious. CONCLUSIONS In day-to-day clinical practice management of PHN, treatment with the 5% lidocaine medicated plaster permitted a significant quantitative reduction in concomitant treatments for neuropathic pain in the overall efficacy population. In the subgroup aged ≥70 years, the quantitative reduction was non-significant. However, in both populations, 5% lidocaine medicated plaster reduced use of TCAs and step 3 analgesics. An improved polymedication status and good tolerability in this likely multimorbid age group indicate that the plaster is a new therapeutic alternative for patients suffering from PHN in France.
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Affiliation(s)
- Florentin Clère
- Centre Hospitalier, Consultation Pluridisciplinaire de la Douleur, Chateauroux, France
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Nalamachu S. Comment: Systematic Review and Meta-Analysis of Efficacy, Safety, and Tolerability Data from Randomized Controlled Trials of Drugs Used to Treat Postherpetic Neuralgia. Ann Pharmacother 2012; 46:764-5; author reply 765. [DOI: 10.1345/aph.1p777a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Affiliation(s)
- Srinivas Nalamachu
- President and Medical Director International Clinical Research Institute Leawood, KS
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Pharmacological management of persistent pain in older persons. THE JOURNAL OF PAIN 2012; 12:S21-9. [PMID: 21396598 DOI: 10.1016/j.jpain.2011.01.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2010] [Revised: 12/20/2010] [Indexed: 12/19/2022]
Abstract
Drugs without a strong evidence base and outside of recommendations are too often prescribed for older adults. Established guidelines such as Beers criteria have identified both specific medications and certain drug classes as inappropriate for older adults, primarily due to adverse effects. Age-related physiological changes in distribution, metabolism, and elimination often alter the effects of pharmacotherapies in older adults. When designing a therapeutic program, all elements contributing to the pathophysiology of painful conditions should be considered, as well as the mechanisms of action of analgesic drug classes. Both appropriate and inappropriate medications for older adults are detailed herein, as well as their contraindications and potential drug-drug or drug-disease interactions. The number needed to treat (NNT) can be useful in considering efficacy, while the safety of a pharmacotherapy is indicated by the calculated number needed to harm (NNH). The NNT is a measure describing the number of patients who require treatment for every 1 who reaches the therapeutic goal, and the NNH describes the number of participants who manifest side effects; these can further be segregated into numbers who withdraw from studies due to intolerable side effects. These parameters, along with a patient's comorbidities and concomitant medications, should be considered when selecting an analgesic and dose regimen. In addition, practitioners should avoid prescribing multiple-drug therapies that have overlapping pharmacodynamics or that may have an adverse pharmacokinetic interaction.
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Hama A, Sagen J. Combination Drug Therapy for Pain following Chronic Spinal Cord Injury. PAIN RESEARCH AND TREATMENT 2012; 2012:840486. [PMID: 22550581 PMCID: PMC3324948 DOI: 10.1155/2012/840486] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 01/06/2012] [Indexed: 12/15/2022]
Abstract
A number of mechanisms have been elucidated that maintain neuropathic pain due to spinal cord injury (SCI). While target-based therapeutics are being developed based on elucidation of these mechanisms, treatment for neuropathic SCI pain has not been entirely satisfactory due in part to the significant convergence of neurological and inflammatory processes that maintain the neuropathic pain state. Thus, a combination drug treatment strategy, wherein several pain-related mechanism are simultaneously engaged, could be more efficacious than treatment against individual mechanisms alone. Also, by engaging several targets at once, it may be possible to reduce the doses of the individual drugs, thereby minimizing the potential for adverse side effects. Positive preclinical and clinical studies have demonstrated improved efficacy of combination drug treatment over single drug treatment in neuropathic pain of peripheral origin, and perhaps such combinations could be utilized for neuropathic SCI pain. At the same time, there are mechanisms that distinguish SCI from peripheral neuropathic pain, so novel combination therapies will be needed.
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Affiliation(s)
- Aldric Hama
- The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, 1095 SW 14th Terrace, Miami, FL 33136, USA
| | - Jacqueline Sagen
- The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, 1095 SW 14th Terrace, Miami, FL 33136, USA
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Differential effects on sensory functions and measures of epidermal nerve fiber density after application of a lidocaine patch (5%) on healthy human skin. Eur J Pain 2012; 15:907-12. [DOI: 10.1016/j.ejpain.2011.03.011] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2010] [Revised: 02/02/2011] [Accepted: 03/28/2011] [Indexed: 11/17/2022]
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de Leon-Casasola O. New developments in the treatment algorithm for peripheral neuropathic pain. PAIN MEDICINE 2011; 12 Suppl 3:S100-8. [PMID: 21752181 DOI: 10.1111/j.1526-4637.2011.01160.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Neuropathic pain often imposes a substantial and unrelenting burden on those individuals who have it; single-agent analgesics typically only reduce pain at best. Worldwide, five sets of treatment recommendations offer insight into managing neuropathic pain, including two European guidelines, one Canadian, one Latin American, and another constructed under the auspices of the International Association for the Study of Pain (IASP). The analgesics common to these guidelines are topical lidocaine, secondary amine tricyclic antidepressants, serotonin and norepinephrine dual reuptake inhibitors, calcium channel α(2)-δ ligands, tramadol, and opioid antagonists. Still, significant knowledge gaps in the treatment of neuropathic pain conditions have hampered the development of algorithms and multimodal approaches. As the evidence base expands, the addition of new comparative trial data will further refine the development of new guidance for clinical management of neuropathic pain. New alternatives for managing neuropathic pain, such as the high-concentration capsaicin patch, will enlarge the treatment armamentarium and potentially impact therapeutic guidelines.
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Affiliation(s)
- Oscar de Leon-Casasola
- School of Medicine and Biomedical Sciences, University at Buffalo, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
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Argoff CE. Review of current guidelines on the care of postherpetic neuralgia. Postgrad Med 2011; 123:134-42. [PMID: 21904096 DOI: 10.3810/pgm.2011.09.2469] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
An unfortunate minority of patients with acute herpes zoster (AHZ) experience pain beyond the typical 4-week duration, and roughly 10% develop the distressing complication of postherpetic neuralgia (PHN), often defined as pain persisting for > 4 months after the onset of the rash. Elderly patients are at increased risk of PHN. The pathophysiology of PHN is complex, likely involving both peripheral and central processes. This complexity may create opportunities for pharmacologic interventions with multiple differing mechanisms of action. Consequently, complementary combinations of pharmacologic agents are frequently more effective than any monotherapy. Current US and international guidelines on the care of patients with PHN are reviewed and interpreted here to facilitate their effective incorporation into the practice of primary care physicians, acknowledging the contrasts that often exist between the clinical trial populations analyzed to craft so-called evidence-based medicine and the individual patients seen in daily practice, many of whom may not have been candidates for those clinical trials. First-line treatments for PHN include tricyclic antidepressants, gabapentin and pregabalin, and the topical lidocaine 5% patch. Opioids, tramadol, capsaicin cream, and the capsaicin 8% patch are recommended as either second- or third-line therapies in different guidelines. Therapies that have demonstrated effectiveness for other types of neuropathic pain are discussed, such as serotonin-norepinephrine reuptake inhibitors, the anticonvulsants carbamazepine and valproic acid, and botulinum toxin. Invasive procedures such as sympathetic blockade, intrathecal steroids, and implantable spinal cord stimulators have been studied for relief of PHN, mainly in patients refractory to noninvasive pharmacologic interventions. The main guidelines considered here are those issued by the American Academy of Neurology for the treatment of postherpetic neuralgia (2004) and general guidelines for the treatment of neuropathic pain issued by the Special Interest Group on Neuropathic Pain of the International Association for the Study of Pain (2007) and the European Federation of Neurological Societies (2010).
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