Topical capsaicin (high concentration) for chronic neuropathic pain in adults

Sheena Derry; Andrew SC Rice; Peter Cole; Toni Tan; R Andrew Moore

doi:10.1002/14651858.CD007393.pub4

Capsaicina tópica (alta concentración) para el dolor neuropático crónico en adultos

Contraer todo Desplegar todo

Referencias

Referencias de los estudios incluidos en esta revisión

Ir a:

estudios excluidos
estudios a la espera de valoración
otras referencias
otras versiones publicadas

Backonja M, Wallace MS, Blonsky ER, Cutler BJ, Malan P Jr, Rauck R, et al, NGX-4010 C107 Study Group. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurology 2008;7(12):1106-12. [DOI: 10.1016/S1474-4422(08)70228-X]

Bischoff JM, Ringsted TK, Petersen M, Sommer C, Uçeyler N, Werner MU. A capsaicin (8%) patch in the treatment of severe persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled trial. PLoS One 2014;9(10):e109144. [DOI: 10.1371/journal.pone.0109144]

Brown S, Simpson DM, Moyle G, Brew BJ, Schifitto G, Larbalestier N, et al. NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials. AIDS Research and Therapy 2013;10(1):5. [DOI: 10.1186/1742-6405-10-5]

Clifford DB, Simpson DM, Brown S, Moyle G, Brew BJ, Conway B, et al, NGX-4010 C119 Study Group. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. Journal of Acquired Immune Deficiency Syndromes 2012;589(2):126-33. [DOI: 10.1097/QAI.0b013e31823e31f7]

Irving GA, Backonja MM, Dunteman E, Blonsky ER, Vanhove GF, Lu SP, et al, NGX-4010 C117 Study Group. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Medicine 2011;12(1):99-109. [DOI: 10.1111/j.1526-4637.2010.01004.x]

Brown S, Simpson DM, Moyle G, Brew BJ, Schifitto G, Larbalestier N, et al. NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials. AIDS Research and Therapy 2013;10(1):5. [DOI: 10.1186/1742-6405-10-5]

Simpson DM, Brown S, Tobias J, NGX-4010 C107 Study Group. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology 2008;70(24):2305-13. [DOI: 10.1212/01.wnl.0000314647.35825.9]

Astellas PharmaEurope BV (Sponsor). A phase III, double-blind, randomized, placebo-controlled, multicenter study evaluating the efficacy and safety of QUTENZA® in subjects with painful diabetic peripheral neuropathy (clinical study results). www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=76 Date first received: 6 February 2012. [ASTELLAS ID: E05-CL-3004]

Astellas Pharma Inc (Responsible party). A phase III, double-blind, randomized, placebo-controlled, multicenter study evaluating the efficacy and safety of QUTENZA® in subjects with painful diabetic peripheral neuropathy. clinicaltrials.gov/ct2/show/NCT01533428 Date first received: 12 February 2012. [ASTELLAS ID: E05-CL-3004] [CTG: NCT01533428]

Simpson DM, Robinson-Papp J, Van J, Stoker M, Jacobs H, Snijder RJ, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. Journal of Pain 2016 Oct 13 [Epub ahead of print]. [DOI: 10.1016/j.jpain.2016.09.008]

Enlace al artículo

Webster LR, Tark M, Rauck R, Tobias JK, Vanhove GF. Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia. BMC Neurology 2010;10:92. [DOI: 10.1186/1471-2377-10-92]

Webster LR, Malan TP, Tuchman MM, Mollen MD, Tobias JK, Vanhove GF. A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Journal of Pain 2010;11(10):972-82. [DOI: 10.1016/j.jpain.2010.01.270]

Referencias de los estudios excluidos de esta revisión

Ir a:

estudios incluidos
estudios a la espera de valoración
otras referencias
otras versiones publicadas

Backonja MM, Malan TP, Vanhove GF, Tobias JK, C102/106 Study Group. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomized, double-blind, controlled study with an open-label extension. Pain Medicine 2010;11(4):600-8. [DOI: 10.1111/j.1526-4637.2009.00793.x]

Referencias de los estudios en espera de evaluación

Ir a:

estudios incluidos
estudios excluidos
otras referencias
otras versiones publicadas

Vanhove T. A multicenter randomized, double-blind, controlled study to evaluate safety, tolerability and preliminary efficacy of two capsaicin concentration variations of NGX-1998 (10% or 20% w/w) in subjects with postherpetic neuralgia (PHN). clinicaltrials.gov/ct2/show/NCT01228838 Date first received: 25 October 2010. [CTG: NCT01228838] [NEUROGESX ID: C204]

Webster L, Bhattacharya S, Wallace M, Wells B, Tobias J, Babbar S. Efficacy and safety of NGX-1998, a novel topical liquid formulation of capsaicin, in patients with postherpetic neuralgia: results of a multi-center, placebo-controlled trial. Journal of Pain 2012;13 (4 Suppl 1):S72. [DOI: 10.1016/j.jpain.2012.01.300]

Referencias adicionales

Ir a:

estudios incluidos
estudios excluidos
estudios a la espera de valoración
otras versiones publicadas

Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. British Journal of Anaesthetics 2011;107(4):490-502. [DOI: 10.1093/bja/aer260]

Azevedo LF, Costa-Pereira A, Mendonça L, Dias CC, Castro-Lopes JM. The economic impact of chronic pain: a nationwide population-based cost-of-illness study in Portugal. European Journal of Health Economics 2016;17(1):87-98. [DOI: 10.1007/s10198-014-0659-4]

Baron R, Wasner G, Binder A. Chronic pain: genes, plasticity, and phenotypes. Lancet Neurology 2012;11(1):19-21. [DOI: 10.1016/S1474-4422(11)70281-2]

Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 2008;136(3):380-7. [DOI: 10.1016/j.pain.2007.08.013]

Bouhassira D, Chassany O, Gaillat J, Hanslik T, Launay O, Mann C, et al. Patient perspective on herpes zoster and its complications: an observational prospective study in patients aged over 50 years in general practice. Pain 2012;153(2):342-9. [DOI: 10.1016/j.pain.2011.10.026]

Burness CB, McCormack PL. Capsaicin 8% patch: a review in peripheral neuropathic pain. Drugs 2016;76:123-34. [DOI: 10.1007/s40265-015-0520-9]

Calvo M, Dawes JM, Bennett DL. The role of the immune system in the generation of neuropathic pain. Lancet Neurology 2012;11(7):629-42. [DOI: 10.1016/S1474-4422(12)70134-5]

Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate pain in millimetres? Pain 1997;72(1-2):95-7.

Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ (Clinical Research Ed) 1995;310:452-4.

Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta-epidemiological study. BMJ 2013;346:f2304. [DOI: 10.1136/bmj.f2304]

Demant DT, Lund K, Vollert J, Maier C, Segerdahl M, Finnerup NB, et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study. Pain 2014;155(11):2263-73. [DOI: 10.1016/j.pain.2014.08.014]

Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No: CD010111. [DOI: 10.1002/14651858.CD010111]

Derry S, Wiffen PJ, Moore RA, Quinlan J. Topical lidocaine for neuropathic pain in adults. Cochrane Database of Systematic Reviews 2014, Issue 7. Art. No: CD010958. [DOI: 10.1002/14651858.CD010958.pub2]

Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. Journal of Pain 2008;9(2):105-21. [DOI: 10.1016/j.jpain.2007.09.005]

Edwards JE, McQuay HJ, Moore RA, Collins SL. Reporting of adverse effects in clinical trials should be improved: lessons from acute postoperative pain. Journal of Pain and Symptom Management 1999;18(6):427-37. [DOI: 10.1016/S0885-3924(99)00093-7]

Astellas PharmaEurope BV (Sponsor). QUTENZATM versus pregabalin in subjects with peripheral neuropathic pain: an open-label, randomized, multicenter, non-inferiority efficacy and tolerability study. www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=83 Date first received: 11 July 2012. [EUDRACT NUMBER: 2011-005872-41]

eMC. Qutenza 179mg cutaneous patch. www.medicines.org.uk/emc/medicine/23156/SPC/qutenza 179mg cutaneous patch/ (accessed 28 April 2012).

Effective Practice and Organisation of Care (EPOC). 23. Worksheets for preparing a Summary of Findings using GRADE. Resources for review authors. Oslo: Norwegian Knowledge Centre for the Health Services. Available at: epoc.cochrane.org/epoc-specific-resources-review-authors (accessed 30 November 2016)2015.

US Department of Health and Human Services. Guidance for industry: skin irritation and sensitization testing of generic transdermal drug products. www.fda.gov/ohrms/dockets/98fr/990236Gd.pdf (accessed 13 December 2016).

Finnerup NB, Scholz J, Attal N, Baron R, Haanpää M, Hansson P, et al. Neuropathic pain needs systematic classification. European Journal of Pain 2013;17(7):953-6. [DOI: 10.1002/j.1532-2149.2012.00282.x]

Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurology 2015;14(2):162-73. [DOI: 10.1016/S1474-4422(14)70251-0]

Gülfe A, Kristensen LE, Saxne T, Jacobsson LT, Petersson IF, Geborek P. Utility-based outcomes made easy: the number needed per quality-adjusted life year gained. An observational cohort study of tumor necrosis factor blockade in inflammatory arthritis from Southern Sweden. Arthritis Care and Research 2010;62(10):1399-406. [DOI: 10.1002/acr.20235]

Gustorff B, Dorner T, Likar R, Grisold W, Lawrence K, Schwarz F, et al. Prevalence of self-reported neuropathic pain and impact on quality of life: a prospective representative survey. Acta Anaesthesiological Scandinavica 2008;52(1):132-6.

Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence - inconsistency. Journal of Clinical Epidemiology 2011;64(12):1294-302. [DOI: 10.1016/j.jclinepi.2011.03.017]

Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso-Coello P, et al. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. Journal of Clinical Epidemiology 2013;66(2):151-7. [DOI: 10.1016/j.jclinepi.2012.01.006]

Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables - binary outcomes. Journal of Clinical Epidemiology 2013;66(2):158-72. [DOI: 10.1016/j.jclinepi.2012.01.012]

Hall GC, Carroll D, McQuay HJ. Primary care incidence and treatment of four neuropathic pain conditions: a descriptive study, 2002-2005. BMC Family Practice 2008;9:26. [DOI: 10.1186/1471-2296-9-26]

Hall GC, Morant SV, Carroll D, Zahava LG, McQuay HJ. An observational descriptive study of the epidemiology and treatment of neuropathic pain in a UK general population. BMC Family Practice 2013;14:28. [DOI: 10.1186/1471-2296-14-28]

Helfert SM, Reimer M, Höper J, Baron R. Individualized pharmacological treatment of neuropathic pain. Clinical Pharmacology and Therapeutics 2015;97(2):135-42. [DOI: 10.1002/cpt.19]

Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.

Hoffman DL, Sadosky A, Dukes EM, Alvir J. How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy? Pain 2010;149(2):194-201. [DOI: 10.1016/j.pain.2009.09.017]

Ikenberg R, Hertel N, Moore RA, Obradovic M, Baxter G, Conway P, et al. Cost-effectiveness of tapentadol prolonged release compared with oxycodone controlled release in the UK in patients with severe non-malignant chronic pain who failed 1st line treatment with morphine. Journal of Medical Economics 2012;15(4):724-36. [DOI: 10.3111/13696998.2012.670174]

Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clinical Trials 1996;17:1-12. [DOI: 10.1016/0197-2456(95)00134-4]

Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, et al. A new definition of neuropathic pain. Pain2011;152(10):2204-5. [DOI: 10.1016/j.pain.2011.06.017]

Google Scholar

Kalso E, Aldington DJ, Moore RA. Drugs for neuropathic pain. BMJ 2013;347:f7339. [DOI: 10.1136/bmj.f7339]

Katusic S, Williams DB, Beard CM, Bergstralh EJ, Kurland LT. Epidemiology and clinical features of idiopathic trigeminal neuralgia and glossopharyngeal neuralgia: similarities and differences, Rochester, Minnesota, 1945-1984. Neuroepidemiology 1991;10:276-81. [DOI: 10.1159/000110284]

Kern KU, Nowack W, Poole C. Treatment of neuropathic pain with the capsaicin 8% patch: is pretreatment with lidocaine necessary? Pain Practice 2014;14(2):E42-50. [DOI: 10.1111/papr.12143]

Knolle E, Zadrazil M, Kovacs GG, Medwed S, Scharbert G, Schemper M. Comparison of cooling and EMLA to reduce the burning pain during capsaicin 8% patch application: a randomized, double-blind, placebo-controlled study. Pain 2013;154(12):2729-36. [DOI: 10.1016/j.pain.2013.08.001]

Koopman JS, Dieleman JP, Huygen FJ, de Mos M, Martin CG, Sturkenboom MC. Incidence of facial pain in the general population. Pain 2009;147(1-3):122-7. [DOI: 10.1016/j.pain.2009.08.023]

L'Abbé KA, Detsky AS, O'Rourke K. Meta-analysis in clinical research. Annals of Internal Medicine 1987;107:224-33. [DOI: 10.7326/0003-4819-107-2-224]

Loke YK, Derry S. Reporting of adverse drug reactions in randomised controlled trials - a systematic survey. BMC Clinical Pharmacology 2001;1:3. [DOI: 10.1186/1472-6904-1-3]

Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No: CD007115. [DOI: 10.1002/14651858.CD007115.pub3]

Moore RA, Gavaghan D, Tramèr MR, Collins SL, McQuay HJ. Size is everything - large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 1998;78(3):209-16. [DOI: 10.1016/S0304-3959(98)00140-7]

Moore RA, Derry S, Makinson GT, McQuay HJ. Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports. Arthritis Research and Therapy 2005;7(3):R644-65. [DOI: 10.1186/ar1704]

Moore RA, Barden J, Derry S, McQuay HJ. Managing potential publication bias. In: McQuay HJ, Kalso E, Moore RA, editors(s). Systematic Reviews in Pain Research: Methodology Refined. Seattle: IASP Press, 2008:15-23. [ISBN: 978-0-931092-69-5]

Moore RA, Derry S, McQuay HJ. Discontinuation rates in clinical trials in musculoskeletal pain: meta-analysis from etoricoxib clinical trial reports. Arthritis Research and Therapy 2008;10(3):R53. [DOI: 10.1186/ar2422]

Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No: CD007076. [DOI: 10.1002/14651858.CD007076.pub2]

Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No: CD007938. [DOI: 10.1002/14651858.CD007938.pub2]

Google Scholar

Moore RA, Gaskell H, Rose P, Allan J. Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject) from clinical trial reports and published trial data. BMC Blood Disorders 2011;11:4. [DOI: 10.1186/1471-2326-11-4]

Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No: CD008242. [DOI: 10.1002/14651858.CD008242.pub2]

Moore RA, Straube S, Eccleston C, Derry S, Aldington D, Wiffen P, et al. Estimate at your peril: imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses. Pain 2012;153(2):265-8. [DOI: 10.1016/j.pain.2011.10.004]

Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. BMJ 2013;346:f2690. [DOI: 10.1136/bmj.f2690]

Moore RA, Straube S, Aldington D. Pain measures and cut-offs - 'no worse than mild pain' as a simple, universal outcome. Anaesthesia 2013;68(4):400-12. [DOI: 10.1111/anae.12148]

Moore RA, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non-cancer pain and chronic neuropathic pain. Pain Practice 2014;14(1):79-94. [DOI: 10.1111/papr.12050]

Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No: CD007938. [DOI: 10.1002/14651858.CD007938.pub3]

Google Scholar

Moore RA, Cai N, Skljarevski V, Tölle TR. Duloxetine use in chronic painful conditions - individual patient data responder analysis. European Journal of Pain 2014;18(1):67-75. [DOI: 10.1002/j.1532-2149.2013.00341.x]

Morris JA, Gardner MJ. Calculating confidence intervals for relative risk, odds ratios and standardised ratios and rates. In: Gardner MJ, Altman DG, editors(s). Statistics with Confidence - Confidence Intervals and Statistical Guidelines. London: British Medical Journal, 1995:50-63.

Mou J, Paillard F, Turnbull B, Trudeau J, Stoker M, Katz NP. Efficacy of Qutenza® (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza Clinical Trials Database. Pain 2013;154(9):1632-9. [DOI: 10.1016/j.pain.2013.04.044]

National Institute for Health and Care Excellence (NICE). Neuropathic pain - pharmacological management: the pharmacological management of neuropathic pain in adults in non-specialist settings, 2013. www.nice.org.uk/guidance/cg173 (accessed 30 November 2016).

Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, et al. Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study. BMJ 2010;341:c3515. [DOI: 10.1136/bmj.c3515]

O'Brien EM, Staud RM, Hassinger AD, McCulloch RC, Craggs JG, Atchison JW, et al. Patient-centered perspective on treatment outcomes in chronic pain. Pain Medicine 2010;11(1):6-15. [DOI: 10.1111/j.1526-4637.2009.00685]

Astellas PharmaEurope BV (Sponsor). A randomized, controlled, long-term safety study evaluating the effect of repeated applications of QUTENZATM plus standard of care versus standard of care alone in patients with painful diabetic peripheral neuropathy. www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=75 Date first received: 10 November 2011. [ASTELLAS ID: E05-CL-3002] [CTG: NCT01478607] [EUDRACT NUMBER: 2009-016458-42]

PaPaS author and referee guidance. papas.cochrane.org/papas-documents (accessed 30 November 2016).

Phillips TJ, Cherry CL, Cox S, Marshall SJ, Rice AS. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials. PLoS One 2010;5(12):e14433.

Rappaport ZH, Devor M. Trigeminal neuralgia: the role of self-sustaining discharge in the trigeminal ganglion. Pain 1994;56:127-38. [DOI: 10.1016/0304-3959(94)90086-8]

The Nordic Cochrane Centre, The Cochrane CollaborationReview Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Simpson DM, Brown S, Tobias JK, Vanhove GF, NGX-4010 C107 Study Group. NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: results of a 52-week open-label study. Clinical Journal of Pain 2014;30(2):134-42. [DOI: 10.1097/AJP.0b013e318287a32f]

Straube S, Derry S, Moore RA, McQuay HJ. Pregabalin in fibromyalgia: meta-analysis of efficacy and safety from company clinical trial reports. Rheumatology 2010;49(4):706-15. [DOI: 10.1093/rheumatology/kep432]

Straube S, Moore RA, Paine J, Derry S, Phillips CJ, Hallier E, et al. Interference with work in fibromyalgia: effect of treatment with pregabalin and relation to pain response. BMC Musculoskeletal Disorders 2011;12:125. [DOI: 10.1186/1471-2474-12-125]

Astellas PharmaEurope BV (Sponsor). A multicentre, single-arm, open-label study of the repeated administration of QUTENZA^TM for the treatment of peripheral neuropathic pain. www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=81 Date first received: 28 October 2010. [EUDRACT NUMBER: 2009-016457-18]

Sultan A, Gaskell H, Derry S, Moore RA. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials. BMC Neurology 2008;8:29. [DOI: 10.1186/1471-2377-8-9]

Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. Journal of Pain 2006;7(4):281-9. [DOI: 10.1016/j.jpain.2005.11.008]

Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008;70(18):1630-5. [DOI: 10.1212/01.wnl.0000282763.29778.59]

Űçeyler N, Sommer C. High-dose capsaicin for the treatment of neuropathic pain: what we know and what we need to know. Pain and Therapy 2014;3(2):73-84. [DOI: 10.1007/s40122-014-0027-1]

van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain 2014;155(4):654-62. [DOI: 10.1016/j.pain.2013.11.013]

van Nooten FE, Charokopou M, Poole C, Treur M. A systematic literature review and network meta-analysis of capsaicin 8% patch versus oral neuropathic pain medications for the treatment of painful diabetic peripheral neuropathy. Value in Health 2015;18(7):A659. [DOI: 10.1016/j.jval.2015.09.2388]

von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron 2012;73(4):638-52. [DOI: 10.1016/j.neuron.2012.02.008]

Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2163-96. [DOI: 10.1016/S0140-6736(12)61729-2]

Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice ASC, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No: CD010567. [DOI: 10.1002/14651858.CD010567.pub2]

Referencias de otras versiones publicadas de esta revisión

Ir a:

estudios incluidos
estudios excluidos
estudios a la espera de valoración
otras referencias

Derry S, Lloyd R, Moore RA, McQuay HJ. Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No: CD007393. [DOI: 10.1002/14651858.CD007393.pub2]

Derry S, Sven-Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No: CD007393. [DOI: 10.1002/14651858.CD007393.pub3]

Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ (Clinical Research Ed) 2004;328(7446):991. [10.1136/bmj.38042.506748.EE]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

estudios excluidos
estudios a la espera de clasificación

Backonja 2008

*Study characteristics*
Methods	RCT, DB, multicentre, parallel groups, single application, 12‐week duration. Patch applied to painful area, up to 1000 cm² Oral pain medication continued without change. Transdermal opioids (morphine equivalent ≤ 60 mg/day) permitted, but not topical analgesics Rescue medication: after application participants allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days Pain assessed daily (average pain for last 24 hours). PGIC assessed at endpoint. Clinic visits at 4, 8, 12 weeks
Participants	Postherpetic neuropathy with at least moderate pain, ≥ 6 months since vesicle crusting. Exclusion: pain in/around facial area N = 402 M = 190, F = 212 Mean age: 71 years Baseline pain: 30 mm to 90 mm (mean 60 mm)
Interventions	(1) Capsaicin patch 8%, n = 206 (2) Control patch, n = 196 Topical local anaesthetic applied for 60 min, then patch applied for 60 min Control patch contained 0.04% capsaicin to mimic AEs
Outcomes	PI: 11‐point numeric pain rating scale (responder: ≥ 30% and ≥ 2‐point reduction from baseline) PGIC: 7‐point scale (responder: much and very much improved) AEs Withdrawals
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Low risk	Remote treatment assignment, using unique number on printed labels affixed to outside of patch envelope
Blinding (performance bias and detection bias) All outcomes	Low risk	Low concentration of capsaicin in "identically formulated" control patch to mimic local skin reaction of active treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified (no details) LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Low risk	206 participants in capsaicin arm,196 participants in control arm

Bischoff 2014

*Study characteristics*
Methods	RCT, DB, PC, parallel group, single application, 12‐week duration. Pain assessment twice daily in 3 days before treatment and clinical visits at 1, 2, 3 months.
Participants	Persistent pain after inguinal herniorrhaphy score ≥ 5/10 for > 6 months Exclusion: bilateral groin pain, allergy to any component of treatment, comorbidity that might interfere with treatment or assessment N = 46 M = 42, F = 4 Mean age: 54 years Baseline pain on movement: 5.5/10 (range 3 to 7)
Interventions	(1) Capsaicin patch 8%, n = 24 (23 treated) (2) Placebo patch, n = 22 Topical local anaesthetic (EMLA; lidocaine + prilocaine) applied for 60 min, then patch applied to groin area for 60 min Cool packs applied to skin for 45 to 60 min after patch removal and cleansing Stable (≥ 4 weeks) analgesic medication continued without change
Outcomes	SPID ‐ difference between groups at 4, 8, 12 weeks AEs Withdrawals
Notes	Oxford Quality Score: R2, DB2, W1. Total = 5/5 Study terminated early due to expiry of placebo patch
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"computer‐generated randomization list"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"placebo patches were identical in appearance and composition (in regard to vehicle substances)". 70% of capsaicin participants and 80% of placebo participants correctly guessed assignment
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Imputation unclear
Size	High risk	< 50 participants per treatment arm

Clifford 2012

*Study characteristics*
Methods	RCT, DB, parallel groups, single application, 12‐week duration. Patches applied to both feet, up to 1120 cm² Oral pain medication continued without change. Transdermal opioids (morphine equivalent ≤ 80 mg/day) permitted, but not topical analgesics, or implanted medical device for pain relief Rescue medication: during application participants allowed oral oxycodone solution (1 mg/mL) and local cooling; after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days, and paracetamol (≤ 3 g/day) throughout Pain assessed daily (average pain for last 24 hours). PGIC assessed at 12 weeks. Clinic visits at 4, 8, 12 weeks
Participants	HIV‐associated distal sensory neuropathy for ≥ 2 months Exclusion: previous use of NGX‐4010 (capsaicin) N = 494 M = 432, F = 62 Mean age: 50 years Baseline pain: 30 mm to 90 mm (mean 60 mm)
Interventions	(1) Capsaicin patch 8% 30 min, n = 167 (2) Capsaicin patch 8% 60 min, n = 165 (3) Placebo patch 30 min, n = 73 (4) Placebo patch 60 min, n = 89 Topical local anaesthetic applied for 60 min, then patch applied for 30 or 60 min Control patch contained 0.04% capsaicin to mimic AEs
Outcomes	PI: 11‐point numeric pain rating scale (responder: ≥ 30% reduction from baseline) PGIC: 7‐point scale (reporting: slightly, much and very much improved) AEs Withdrawals
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "allocation scheme prepared by Fisher Clinical Services"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not described as identical; "low‐dose capsaicin control patches were used instead of placebo to provide effective blinding ..."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Unclear risk	50 to 200 participants per treatment arm.

Irving 2011

*Study characteristics*
Methods	RCT, DB, multicentre, parallel‐group, single application, 12‐week duration. Patch applied to painful area, up to 1120 cm² Oral pain medication continued without change. Transdermal opioids (morphine equivalent ≤ 60 mg/day) permitted, but not topical analgesics Pain assessed daily (average pain for last 24 hours). PGIC assessed at 4, 8, 12 weeks. Clinic visits at 4, 8, 12 weeks
Participants	Postherpetic neuropathy with at least moderate pain, ≥ 6 months since vesicle crusting. Exclusion: pain above neck area N = 416 M = 190, F = 226 Mean age: 70 years Baseline pain: 30 mm to 90 mm (mean 57 mm)
Interventions	(1) Capsaicin patch 8%, n = 212 (2) Control patch, n = 204 Topical local anaesthetic applied for 60 min, then patch applied for 60 min Control patch contained 0.04% capsaicin to mimic AEs
Outcomes	PI: 11‐point numeric pain rating scale (responder: ≥ 30%, ≥ 50%, and ≥ 2‐point reduction from baseline) PGIC: 7‐point scale (responder: much and very much improved) AEs Withdrawals
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "allocation scheme prepared by Fisher Clinical Services"
Allocation concealment (selection bias)	Low risk	Each kit "designated by a unique kit number, which was printed on the investigational drug label affixed to the outer bag enclosure and on each individual patch envelope"
Blinding (performance bias and detection bias) All outcomes	Low risk	"The NGX‐4010 [capsaicin] and control patches were identical in appearance, as were the blinded study kits"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis.
Size	Low risk	> 200 participants per treatment arm

Simpson 2008

*Study characteristics*
Methods	RCT, DB, multicentre, parallel groups, single application, 12‐week duration. Patches applied to both feet, up to maximum 1000 cm² Oral pain medication continued without change. No topical analgesics During application participants allowed oral oxycodone solution (1 mg/mL) or equivalent, after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 7 days Pain assessed daily (average pain for last 24 hours). PGIC assessed at 12 weeks. Clinic visits at 4, 8, 12 weeks
Participants	HIV‐associated distal sensory polyneuropathy with ≥ 2 months' moderate to severe pain in both feet N = 307 M = 286, F = 21 Mean age: 48 years (range 29 to 74) Baseline pain: 30 mm to 90 mm (mean ~ 60 mm)
Interventions	(1) Capsaicin patch 8% 30 min, n = 72 (2) Capsaicin patch 8% 60 min, n = 78 (3) Capsaicin patch 8% 90 min, n = 75 (4) Control patch, n = 82 Topical local anaesthetic applied for 60 min, then patch applied for 30, 60, or 90 min Control patch contained 0.04% capsaicin to mimic AEs
Outcomes	PI: 11‐point numeric pain rating scale (responder: ≥ 30% reduction from baseline) PGIC: 7‐point scale (responder: much and very much improved) AEs Withdrawals
Notes	Oxford Quality Score: R1, DB1, W1. Total = 3/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of randomisation not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Control patch contained a low concentration of capsaicin to mimic local skin reaction of active treatment. Although it does not say "identical" or use similar wording, we judged this to be low risk
Incomplete outcome data (attrition bias) All outcomes	Low risk	BOCF or 'no improvement' imputed for missing values for dichotomous data analyses
Size	Unclear risk	50 to 200 participants per treatment arm

STEP 2014

*Study characteristics*
Methods	R, DB, multicentre, parallel group, PC, single application, 12‐week duration. Pain assessed daily
Participants	Painful diabetic neuropathy, distal, symmetrical, > 1 year (score > 3 on Michigan Neuropathy Screening Instrument), glycated haemoglobin ≤ 11% and history indicating control, 24‐hour PI ≥ 4/10 in screening period, stable doses of analgesics for ≥ 4 weeks before screening N = 369 M = 215, F = 154 Mean age: 63 years (range 33 to 89) Mean baseline pain: 6.5/10
Interventions	(1) Capsaicin patch 8%, n =186 (2) Placebo patch, n = 183 Up to 4 patches applied to painful areas of feet Topical anaesthetic cream applied according to prescribing information, then patch applied for 30 min Stable concomitant neuropathic pain medication (antiepileptic or antidepressant drugs) allowed if unchanged
Outcomes	≥ 30% and ≥ 50% PI reduction over weeks 2 to 8 and 2 to 12 compared with baseline PGIC much and very much improved at 8 and 12 weeks AEs Withdrawals
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of randomisation not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	"The placebo patches were visually and cosmetically indistinguishable from the active capsaicin patches."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Imputation unclear
Size	Unclear risk	50 to 200 participants per treatment arm

Webster 2010a

*Study characteristics*
Methods	RCT, DB, multicentre, parallel‐group, single application, 12‐week duration. Patch applied to painful area, up to 1120 cm² Oral pain medication continued without change. Transdermal opioids (morphine equivalent ≤ 60 mg/day) permitted, but not topical analgesics Rescue medication: during application participants allowed oral oxycodone solution (1 mg/mL) and local cooling; after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days, and paracetamol (≤ 2 g/day) throughout Pain assessed daily (average pain for last 24 hours). PGIC assessed at 4, 8, 12 weeks. Clinic visits at 4, 8, 12 weeks
Participants	Postherpetic neuropathy with at least moderate pain, ≥ 6 months since vesicle crusting. Exclusion: pain in/around facial area N = 299 M = 150, F = 149 Mean age: 71 years Baseline pain: 30 mm to 90 mm (mean 55 mm)
Interventions	(1) Capsaicin patch 8% 30 min, n = 72 (2) Capsaicin patch 8% 60 min, n = 77 (3) Capsaicin patch 8% 90 min, n = 73 (4) Control patch, 30, 60, 90 min pooled for analysis, n = 77 Topical local anaesthetic applied for 60 min, then patch applied for 30, 60 or 90 min Control patch contained 0.04% capsaicin to mimic AEs
Outcomes	PI: 11‐point numeric pain rating scale (responder: ≥ 30%, ≥ 50%, and ≥ 2‐point reduction from baseline) PGIC: 7‐point scale (reporting: slightly, much and very much improved) AEs Withdrawals
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "randomisation scheme prepared by Cardinal Health"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	"identically appearing control patches"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Unclear risk	50 to 200 participants per treatment arm

Webster 2010b

*Study characteristics*
Methods	RCT, DB, multicentre, parallel‐group, single application, 12‐week duration. Patch applied to painful area, up to 1000 cm² Oral pain medication continued without change. Transdermal opioids (morphine equivalents ≤ 60 mg/day) permitted, but not topical analgesics Rescue medication: during application participants allowed oral oxycodone solution (1 mg/mL) and local cooling; after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days, and paracetamol (≤ 2 g/day) throughout Pain assessed daily (average pain for last 24 hours). PGIC assessed at 4, 8, 12 weeks. Clinic visits at 4, 8, 12 weeks
Participants	Postherpetic neuropathy with at least moderate pain, ≥ 6 months since vesicle crusting. Exclusion: pain in/around facial area N = 155 M = 72, F = 83 Mean age: 70 years Baseline pain: 30 mm to 90 mm (mean 53 mm)
Interventions	(1) Capsaicin patch 8%, n = 102 (2) Control patch, n = 53 Topical local anaesthetic applied for 60 min, then patch applied for 60 min Control patch contained 0.04% capsaicin to mimic AEs
Outcomes	PI: 11‐point numeric pain rating scale (responder: ≥ 30%, ≥ 50%, and ≥ 2‐point reduction from baseline) PGIC: 7‐point scale (responder: much and very much improved) AEs Withdrawals
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "randomisation scheme prepared by Cardinal Health"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	"identically‐appearing ...... control patch"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Unclear risk	50 to 200 participants per treatment arm

AE: adverse event; BOCF: baseline observation carried forward; DB: double‐blind(ing); F: female; LOCF: last observation carried forward; M: male; min: minute; N: number of participants in study; n: number of participants in treatment arm; PC: placebo‐controlled; PGIC: Patient Global Impression of Change; PI: pain intensity; R: randomisation; RCT: randomised controlled trial; W: withdrawals.

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos
estudios a la espera de clasificación

Study	Reason for exclusion
Backonja 2010	Study duration only 4 weeks

Characteristics of studies awaiting classification [ordered by study ID]

Ir a:

estudios incluidos
estudios excluidos

NCT01228838

Methods	RCT, DB, multicentre, parallel groups, single application, 12‐week duration Treatment applied for 5 minutes
Participants	Postherpetic neuropathy with > 6 months of pain since vesicle crusting Baseline pain: 4/10 to 9/10 Age: 18 to 90 years
Interventions	Capsaicin topical liquid 10% Capsaicin topical liquid 20% Placebo Stable pain medications continued unchanged throughout study
Outcomes	Participants with ≥ 30% decrease in pain from baseline at weeks 8 and 12 Participants with ≥ 2‐unit decrease in pain from baseline at weeks 8 and 12
Notes	Primary completion date September 2011. No results posted as of March 2016

DB: double‐blind; RCT: randomised controlled trial.

Data and analyses

Open in table viewer

Comparison 1. High‐concentration (8%) capsaicin versus control (single dose)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Postherpetic neuralgia (PHN) ‐ at least 50% pain intensity reduction over weeks 2 to 8 Show forest plot	3	870	Risk Ratio (M‐H, Fixed, 95% CI)	1.44 [1.12, 1.86]
Open in figure viewer Analysis 1.1 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 1: Postherpetic neuralgia (PHN) ‐ at least 50% pain intensity reduction over weeks 2 to 8
1.1.1 Using 30‐minute application	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	2.95 [0.73, 11.88]
1.1.2 Using 60‐minute application	3	674	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [1.03, 1.75]
1.1.3 Using 90‐minute application	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	2.02 [0.64, 6.33]
1.2 PHN ‐ at least 50% pain intensity reduction over 2 to 12 weeks Show forest plot	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.00, 1.71]
Open in figure viewer Analysis 1.2 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 2: PHN ‐ at least 50% pain intensity reduction over 2 to 12 weeks
1.3 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 8 Show forest plot	4	1268	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.13, 1.52]
Open in figure viewer Analysis 1.3 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 3: PHN ‐ at least 30% pain intensity reduction over weeks 2 to 8
1.3.1 Using 30‐minute application	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.67, 2.69]
1.3.2 Using 60‐minute application	4	1072	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [1.12, 1.52]
1.3.3 Using 90‐minute application	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	1.48 [0.74, 2.95]
1.4 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 12 Show forest plot	3	973	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [1.07, 1.45]
Open in figure viewer Analysis 1.4 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 4: PHN ‐ at least 30% pain intensity reduction over weeks 2 to 12
1.5 PHN ‐ Patient Global Impression of ChangePGIC much or very much improved at 8 and 12 weeks Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.5 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 5: PHN ‐ Patient Global Impression of ChangePGIC much or very much improved at 8 and 12 weeks
1.5.1 At 8 weeks	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [1.10, 1.84]
1.5.2 At 12 weeks	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.55 [1.20, 1.99]
1.6 HIV‐neuropathy ‐ at least 30% pain intensity reduction over weeks 2 to 12 Show forest plot	2	801	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [1.09, 1.68]
Open in figure viewer Analysis 1.6 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 6: HIV‐neuropathy ‐ at least 30% pain intensity reduction over weeks 2 to 12
1.6.1 Using 30‐minute application	2	340	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [1.14, 2.46]
1.6.2 Using 60‐minute application	2	359	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.84, 1.44]
1.6.3 Using 90‐minute application	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	1.94 [0.83, 4.53]
1.7 Local skin reactions ‐ group 1 Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.7 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 7: Local skin reactions ‐ group 1
1.7.1 Erythema	4	1355	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [1.32, 1.54]
1.7.2 Pain	4	1355	Risk Ratio (M‐H, Fixed, 95% CI)	2.26 [1.98, 2.59]
1.7.3 Papules	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	3.58 [1.87, 6.85]
1.7.4 Pruritus	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	1.99 [0.98, 4.03]
1.7.5 Oedema	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	2.98 [1.44, 6.18]
1.8 Local skin reactions ‐ group 2 Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.8 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 8: Local skin reactions ‐ group 2
1.8.1 Erythema	1	129	Risk Ratio (M‐H, Fixed, 95% CI)	6.31 [0.35, 114.82]
1.8.2 Pain	4	1105	Risk Ratio (M‐H, Fixed, 95% CI)	2.39 [1.41, 4.05]
1.8.3 Papules	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.59, 4.24]
1.8.4 Pruritus	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.57 [0.98, 2.50]
1.8.5 Oedema	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.75, 2.39]
1.9 Patch tolerability Show forest plot	7		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.9 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 9: Patch tolerability
1.9.1 < 90% of application time	6	2074	Risk Ratio (M‐H, Fixed, 95% CI)	3.27 [1.17, 9.15]
1.9.2 Dermal irritation score > 2 at 2 hours	3	1065	Risk Ratio (M‐H, Fixed, 95% CI)	11.80 [4.04, 34.48]
1.9.3 Dermal irritation score > 0 at 2 hours	2	606	Risk Ratio (M‐H, Fixed, 95% CI)	2.28 [1.60, 3.26]
1.9.4 Pain medication 0 to 5 days	7	2442	Risk Ratio (M‐H, Fixed, 95% CI)	2.52 [2.18, 2.92]
1.10 Serious adverse events Show forest plot	7	1993	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.70, 1.86]
Open in figure viewer Analysis 1.10 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 10: Serious adverse events
1.11 Withdrawals Show forest plot	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.11 Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 11: Withdrawals
1.11.1 Adverse events	8	2487	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.36, 1.78]
1.11.2 Lack of efficacy	6	2073	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.32, 1.02]

Figure 1

Study flow diagram.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Forest plot of comparison: 1 High‐concentration (8%) capsaicin versus control (single dose), outcome: 1.1 Postherpetic neuralgia ‐ at least 50% pain intensity reduction over weeks 2 to 8.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Forest plot of comparison: 1 High‐concentration (8%) capsaicin versus control (single dose), outcome: 1.5 Postherpetic neuralgia ‐ Patient Global Impression of Change much or very much improved at 8 and 12 weeks.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 5

Forest plot of comparison: 1 High‐concentration (8%) capsaicin versus control (single dose), outcome: 1.6 HIV‐neuropathy ‐ at least 30% pain intensity reduction over weeks 2 to 12.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 6

Forest plot of comparison: 1 High‐concentration (8%) capsaicin versus control (single dose), outcome: 1.10 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 1: Postherpetic neuralgia (PHN) ‐ at least 50% pain intensity reduction over weeks 2 to 8

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 2: PHN ‐ at least 50% pain intensity reduction over 2 to 12 weeks

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 3: PHN ‐ at least 30% pain intensity reduction over weeks 2 to 8

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 4: PHN ‐ at least 30% pain intensity reduction over weeks 2 to 12

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 5: PHN ‐ Patient Global Impression of ChangePGIC much or very much improved at 8 and 12 weeks

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 6: HIV‐neuropathy ‐ at least 30% pain intensity reduction over weeks 2 to 12

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 7: Local skin reactions ‐ group 1

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.8

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 8: Local skin reactions ‐ group 2

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.9

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 9: Patch tolerability

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.10

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 10: Serious adverse events

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.11

Comparison 1: High‐concentration (8%) capsaicin versus control (single dose), Outcome 11: Withdrawals

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings 1. High‐concentration (8%) capsaicin patch compared with control patch (0.4%) for postherpetic neuralgia

Outcomes	Outcome with intervention	Outcome with comparator	RR, NNT, NNH, NNTp (95% CI)	Number of studies, participants, events	Quality of the evidence (GRADE)	Comments
High‐concentration (8%) capsaicin patch compared with control patch (0.4%) for postherpetic neuralgia
Patient or population: adults with postherpetic neuralgia Settings: community Intervention: high‐concentration (8%) capsaicin patch, single application Comparison: control patch (0.4% capsaicin), single application
Substantial benefit
PGICvery much improved, week 8 and week 12	No data	No data	‐	‐	Very low	No data
Moderate benefit
PGICmuch or very much improved, week 8	360 in 1000	250 in 1000	RR 1.4 (1.1 to 1.8) NNT 8.8 (5.3 to 26)	2 studies, 571 participants, 178 events	Moderate	Downgraded 1 level due to susceptibility to publication bias
PGIC much or very much improved, week 12	390 in 1000	250 in 1000	RR 1.6 (1.2 to 2.0) NNT 7.0 (4.6 to 15)	2 studies, 571 participants, 189 events	Moderate	Downgraded 1 level due to susceptibility to publication bias
Harm ‐ all conditions combined
Withdrawals due to lack of efficacy	15 in 1000	31 in 1000	RR 0.58 (0.32 to 1.04) NNTp 64 (34 to 610)	6 studies, 2073 participants, 44 events	Moderate	Downgraded 1 level due to imprecision (few events, wide CI)
Withdrawals due to adverse events	8.0 in 1000	9.2 in 1000	RR 0.80 (0.36 to 1.8) NNTp not calculated	8 studies, 2487 participants, 21 events	Moderate	Downgraded 1 level due to sparse data (few events)
Serious adverse events	35 in 1000	32 in 1000	RR 1.1 (0.70 to 1.8) NNH not calculated	7 studies, 1993 participants, 67 events	Moderate	Downgraded 1 level due to sparse data (few events)
Death	4 events	2 events	Not calculated	8 studies, 2487 participants	Very low	Downgraded 3 levels as only six events, so no better grading possibleNo death was judged related to study medication by study authors
CI: confidence interval; NNH: number needed to treat for one additional harmful outcome; NNT: number needed to treat for one additional beneficial outcome; NNTp: number needed to treat to prevent one withdrawal event; PGIC: Patient Global Impression of Change; RR: risk ratio.
Descriptors for levels of evidence (EPOC 2015): High quality: This research provides a very good indication of the likely effect. The likelihood that the effect will be substantially different^† is low. Moderate quality: This research provides a good indication of the likely effect. The likelihood that the effect will be substantially different^† is moderate. Low quality: This research provides some indication of the likely effect. However, the likelihood that it will be substantially different^† is high. Very low quality: This research does not provide a reliable indication of the likely effect. The likelihood that the effect will be substantially different^† is very high. ^† Substantially different: a large enough difference that it might affect a decision.

Summary of findings 1. High‐concentration (8%) capsaicin patch compared with control patch (0.4%) for postherpetic neuralgia

Ir a la tabla de la revisión

Comparison 1. High‐concentration (8%) capsaicin versus control (single dose)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Postherpetic neuralgia (PHN) ‐ at least 50% pain intensity reduction over weeks 2 to 8 Show forest plot	3	870	Risk Ratio (M‐H, Fixed, 95% CI)	1.44 [1.12, 1.86]

1.1.1 Using 30‐minute application	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	2.95 [0.73, 11.88]
1.1.2 Using 60‐minute application	3	674	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [1.03, 1.75]
1.1.3 Using 90‐minute application	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	2.02 [0.64, 6.33]
1.2 PHN ‐ at least 50% pain intensity reduction over 2 to 12 weeks Show forest plot	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.00, 1.71]

1.3 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 8 Show forest plot	4	1268	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.13, 1.52]

1.3.1 Using 30‐minute application	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.67, 2.69]
1.3.2 Using 60‐minute application	4	1072	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [1.12, 1.52]
1.3.3 Using 90‐minute application	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	1.48 [0.74, 2.95]
1.4 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 12 Show forest plot	3	973	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [1.07, 1.45]

1.5 PHN ‐ Patient Global Impression of ChangePGIC much or very much improved at 8 and 12 weeks Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.5.1 At 8 weeks	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [1.10, 1.84]
1.5.2 At 12 weeks	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.55 [1.20, 1.99]
1.6 HIV‐neuropathy ‐ at least 30% pain intensity reduction over weeks 2 to 12 Show forest plot	2	801	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [1.09, 1.68]

1.6.1 Using 30‐minute application	2	340	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [1.14, 2.46]
1.6.2 Using 60‐minute application	2	359	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.84, 1.44]
1.6.3 Using 90‐minute application	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	1.94 [0.83, 4.53]
1.7 Local skin reactions ‐ group 1 Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.7.1 Erythema	4	1355	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [1.32, 1.54]
1.7.2 Pain	4	1355	Risk Ratio (M‐H, Fixed, 95% CI)	2.26 [1.98, 2.59]
1.7.3 Papules	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	3.58 [1.87, 6.85]
1.7.4 Pruritus	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	1.99 [0.98, 4.03]
1.7.5 Oedema	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	2.98 [1.44, 6.18]
1.8 Local skin reactions ‐ group 2 Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.8.1 Erythema	1	129	Risk Ratio (M‐H, Fixed, 95% CI)	6.31 [0.35, 114.82]
1.8.2 Pain	4	1105	Risk Ratio (M‐H, Fixed, 95% CI)	2.39 [1.41, 4.05]
1.8.3 Papules	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.59, 4.24]
1.8.4 Pruritus	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.57 [0.98, 2.50]
1.8.5 Oedema	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.75, 2.39]
1.9 Patch tolerability Show forest plot	7		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.9.1 < 90% of application time	6	2074	Risk Ratio (M‐H, Fixed, 95% CI)	3.27 [1.17, 9.15]
1.9.2 Dermal irritation score > 2 at 2 hours	3	1065	Risk Ratio (M‐H, Fixed, 95% CI)	11.80 [4.04, 34.48]
1.9.3 Dermal irritation score > 0 at 2 hours	2	606	Risk Ratio (M‐H, Fixed, 95% CI)	2.28 [1.60, 3.26]
1.9.4 Pain medication 0 to 5 days	7	2442	Risk Ratio (M‐H, Fixed, 95% CI)	2.52 [2.18, 2.92]
1.10 Serious adverse events Show forest plot	7	1993	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.70, 1.86]

1.11 Withdrawals Show forest plot	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.11.1 Adverse events	8	2487	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.36, 1.78]
1.11.2 Lack of efficacy	6	2073	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.32, 1.02]

Comparison 1. High‐concentration (8%) capsaicin versus control (single dose)

Ir a la tabla de la revisión

	Idioma de la Revisión Cochrane Escoja su idioma de preferencia para las revisiones Cochrane y otros contenidos. Las secciones sin una traducción aparecerán en inglés.

	Idioma de la web Escoja su idioma de preferencia para la web de la Biblioteca Cochrane.

Idioma de la Revisión Cochrane

Idioma de la web

Referencias

Referencias de los estudios incluidos en esta revisión

Backonja 2008 {published data only}

Bischoff 2014 {published data only}

Clifford 2012 {published data only}

Irving 2011 {published data only}

Simpson 2008 {published data only}

STEP 2014 {unpublished data only}

Webster 2010a {published data only}

Webster 2010b {published data only}

Referencias de los estudios excluidos de esta revisión

Backonja 2010 {published data only}

Referencias de los estudios en espera de evaluación

NCT01228838 {published data only}

Referencias adicionales

Anand 2011

Azevedo 2016

Baron 2012

Bouhassira 2008

Bouhassira 2012

Burness 2016

Calvo 2012

Collins 1997

Cook 1995

Dechartres 2013

Demant 2014

Derry 2012

Derry 2014

Dworkin 2008

Edwards 1999

ELEVATE 2014

eMC 2012

EPOC 2015

FDA 1999

Finnerup 2013

Finnerup 2015

Gülfe 2010

Gustorff 2008

Guyatt 2011

Guyatt 2013a

Guyatt 2013b

Hall 2008

Hall 2013

Helfert 2015

Higgins 2011

Hoffman 2010

Ikenberg 2012

Jadad 1996

Jensen 2011

Kalso 2013

Katusic 1991

Kern 2014

Knolle 2013

Koopman 2009

L'Abbé 1987

Loke 2001

Lunn 2014

Moore 1998

Moore 2005

Moore 2008a

Moore 2008b

Moore 2009

Moore 2011a

Moore 2011b

Moore 2012a

Moore 2012b

Moore 2013a

Moore 2013b

Moore 2014a

Moore 2014b

Moore 2014c

Morris 1995

Mou 2013

NICE 2013

Nüesch 2010

O'Brien 2010

PACE 2014

PaPaS 2012