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Meta-Analysis
. 2016 Nov 16;11(11):CD008320.
doi: 10.1002/14651858.CD008320.pub3.

Pharmacological interventions for pruritus in adult palliative care patients

Waldemar Siemens  1 , Carola Xander, Joerg J Meerpohl, Sabine Buroh, Gerd Antes, Guido Schwarzer, Gerhild Becker
Affiliations
Meta-Analysis

Pharmacological interventions for pruritus in adult palliative care patients

Waldemar Siemens et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: This is an update of the original Cochrane review published in 2013 (Issue 6). Pruritus occurs in patients with disparate underlying diseases and is caused by different pathologic mechanisms. In palliative care patients, pruritus is not the most prevalent but is one of the most puzzling symptoms. It can cause considerable discomfort and affects patients' quality of life.

Objectives: To assess the effects of different pharmacological treatments for preventing or treating pruritus in adult palliative care patients.

Search methods: For this update, we searched CENTRAL (the Cochrane Library), and MEDLINE (OVID) up to 9 June 2016 and Embase (OVID) up to 7 June 2016. In addition, we searched trial registries and checked the reference lists of all relevant studies, key textbooks, reviews and websites, and we contacted investigators and specialists in pruritus and palliative care regarding unpublished data.

Selection criteria: We included randomised controlled trials (RCTs) assessing the effects of different pharmacological treatments, compared with a placebo, no treatment, or an alternative treatment, for preventing or treating pruritus in palliative care patients.

Data collection and analysis: Two review authors independently assessed the identified titles and abstracts, performed data extraction and assessed the risk of bias and methodological quality. We summarised the results descriptively and quantitatively (meta-analyses) according to the different pharmacological interventions and the diseases associated with pruritus. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 10 'Summary of findings' tables.

Main results: In total, we included 50 studies and 1916 participants in the review. We added 10 studies with 627 participants for this update. Altogether, we included 39 different treatments for pruritus in four different patient groups.The overall risk of bias profile was heterogeneous and ranged from high to low risk. However, 48 studies (96%) had a high risk of bias due to low sample size (i.e. fewer than 50 participants per treatment arm). Using GRADE criteria, we downgraded our judgement on the quality of evidence to moderate in seven and to low in three comparisons for our primary outcome (pruritus), mainly due to imprecision and risk of bias.In palliative care participants with pruritus of different nature, the treatment with the drug paroxetine, a selective serotonin reuptake inhibitor, reduced pruritus by 0.78 points (numerical analogue scale from 0 to 10; 95% confidence interval (CI) -1.19 to -0.37; one RCT, N = 48, quality of evidence: moderate) compared to placebo.For participants suffering from uraemic pruritus (UP), gabapentin was more effective than placebo (visual analogue scale (VAS): 0 to 10), mean difference (MD) -5.91, 95% CI -6.87 to -4.96; two RCTs, N = 118, quality of evidence: moderate). The κ-opioid receptor agonist nalfurafine showed amelioration of UP (VAS 0 to 10, MD -0.95, 95% CI -1.32 to -0.58; three RCTs, N = 422, quality of evidence: moderate) and only few adverse events. Moreover, cromolyn sodium relieved UP participants from pruritus by 2.94 points on the VAS (0 to 10) (95% CI -4.04 to -1.83; two RCTs, N = 100, quality of evidence: moderate) compared to placebo.In participants with cholestatic pruritus (CP), data favoured rifampin (VAS: 0 to 100, MD -24.64, 95% CI -31.08 to -18.21; two RCTs, N = 42, quality of evidence: low) and flumecinol (RR > 1 favours treatment group; RR 1.89, 95% CI 1.05 to 3.39; two RCTs, N = 69, quality of evidence: low) and showed a low incidence of adverse events in comparison with placebo. The opioid antagonist naltrexone reduced pruritus for participants with CP (VAS: 0 to 10, MD -2.26, 95% CI -3.19 to -1.33; two RCTs, N = 52, quality of evidence: moderate) compared to placebo. However, effects in participants with UP were inconclusive (percentage difference -12.30%, 95% CI -25.82% to 1.22%, one RCT, N = 32). Furthermore, large doses of opioid antagonists (e.g. naltrexone) could be inappropriate in palliative care patients because of the risk of reducing analgesia.For participants with HIV-associated pruritus, it is uncertain whether drug treatment with hydroxyzine hydrochloride, pentoxifylline, triamcinolone or indomethacin reduces pruritus because the evidence was of very low quality (e.g. small sample size, lack of blinding).

Authors' conclusions: Different interventions tended to be effective for CP and UP. However, therapies for patients with malignancies are still lacking. Due to the small sample sizes in most meta-analyses and the heterogeneous methodological quality of the included trials, the results should be interpreted cautiously in terms of generalisability.

PubMed Disclaimer

Conflict of interest statement

WS: none known.

CX: none known.

JM: none known.

SB: none known.

GA: none known.

GS: none known.

GB: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 1 A) Pruritus on VAS scale (0‐10 cm) in CP participants.
1.2
1.2. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 2 A) Subgroup analysis by study design: pruritus on VAS scale (0‐10 cm) in CP participants.
1.3
1.3. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 3 A) Sensitivity analysis: random‐effects model; pruritus on VAS scale (0‐10 cm) in CP participants.
1.4
1.4. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 4 B) % difference for pruritus on VAS scale (0‐10 cm) in UP and CP participants.
1.5
1.5. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 5 B) Subgroup analysis by nature of pruritus and study design; % difference for pruritus on VAS scale (0‐10 cm).
1.6
1.6. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 6 B) Sensitivity analysis: random‐effects model; % difference for pruritus on VAS scale (0‐10) in UP and CP participants.
1.7
1.7. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 7 C) Risk for at least one adverse event per participant in UP and CP participants; cross‐over design.
1.8
1.8. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 8 C) Subgroup analysis by nature of pruritus; risk for at least one adverse event per participant; cross‐over design.
1.9
1.9. Analysis
Comparison 1 Naltrexone versus placebo, Outcome 9 C) Sensitivity analysis: random‐effects model; risk for at least one adverse event per participant; UP and CP patients; cross‐over design.
2.1
2.1. Analysis
Comparison 2 Nalfurafine versus placebo, Outcome 1 A) Pruritus on VAS scale (0‐10 cm) in UP participants; parallel‐group design; Wikström b: Wikström a (week 2) + period 1 Wikström b.
2.2
2.2. Analysis
Comparison 2 Nalfurafine versus placebo, Outcome 2 A) Sensitivity analysis: random‐effects model; pruritus on VAS scale (0‐10 cm) in UP participants; parallel‐group design; Wikström b: Wikström a (week 2) + period 1 Wikström b.
2.3
2.3. Analysis
Comparison 2 Nalfurafine versus placebo, Outcome 3 B) Risk for at least one adverse drug reaction (ADR) per participant in UP participants; parallel‐group and cross‐over design.
2.4
2.4. Analysis
Comparison 2 Nalfurafine versus placebo, Outcome 4 B) Sensitivity analysis: random‐effects model; risk for at least one adverse event per participant; UP participants; parallel‐group and cross‐over design.
3.1
3.1. Analysis
Comparison 3 Ondansetron versus placebo or standard medication, Outcome 1 A) Pruritus on VAS scale (0‐10 cm) in UP and CP participants.
3.2
3.2. Analysis
Comparison 3 Ondansetron versus placebo or standard medication, Outcome 2 A) Subgroup analysis by nature of pruritus and study design; pruritus on VAS scale (0‐10 cm).
3.3
3.3. Analysis
Comparison 3 Ondansetron versus placebo or standard medication, Outcome 3 A) Sensitivity analysis: random‐effects model; pruritus on VAS scale (0‐10 cm) in UP and CP participants.
3.4
3.4. Analysis
Comparison 3 Ondansetron versus placebo or standard medication, Outcome 4 B) Risk for at least one adverse event per participant in UP and CP participants.
3.5
3.5. Analysis
Comparison 3 Ondansetron versus placebo or standard medication, Outcome 5 B) Subgroup analysis by nature of pruritus and study design; risk for at least one adverse event per participant.
3.6
3.6. Analysis
Comparison 3 Ondansetron versus placebo or standard medication, Outcome 6 B) Sensitivity analysis: random‐effects model; risk for at least one adverse event per participant in UP and CP participants.
4.1
4.1. Analysis
Comparison 4 Gabapentin versus placebo, Outcome 1 A) Pruritus on VAS scale (0‐10 cm) in UP participants.
4.2
4.2. Analysis
Comparison 4 Gabapentin versus placebo, Outcome 2 A) Subgroup analysis by study design; pruritus on VAS scale (0‐10 cm) in UP participants.
4.3
4.3. Analysis
Comparison 4 Gabapentin versus placebo, Outcome 3 A) Sensitivity analysis: random‐effects model; pruritus on VAS scale (0‐10 cm); UP participants.
5.1
5.1. Analysis
Comparison 5 Rifampicin versus placebo or standard medication, Outcome 1 A) Pruritus on VAS scale (0‐100 mm) in CP participants; cross‐over design.
5.2
5.2. Analysis
Comparison 5 Rifampicin versus placebo or standard medication, Outcome 2 A) Sensitivity analysis: random‐effects model; pruritus on VAS scale (0‐100 mm) in CP participants; cross‐over design.
5.3
5.3. Analysis
Comparison 5 Rifampicin versus placebo or standard medication, Outcome 3 B) Subgroup analysis by control; SMD: pruritus on different scales; CP participants; cross‐over design.
5.4
5.4. Analysis
Comparison 5 Rifampicin versus placebo or standard medication, Outcome 4 B) Sensitivity analysis: random‐effects model; subgroup analysis by control; SMD: pruritus on different scales; CP patients; cross‐over design.
6.1
6.1. Analysis
Comparison 6 Flumecinol versus placebo, Outcome 1 A) Pruritus: significant improvement (yes/no); CP participants; parallel group design.
6.2
6.2. Analysis
Comparison 6 Flumecinol versus placebo, Outcome 2 A) Subgroup analysis by dosage; pruritus: significant improvement (yes/no); CP participants; parallel‐group design.
6.3
6.3. Analysis
Comparison 6 Flumecinol versus placebo, Outcome 3 A) Sensitivity analysis: random‐effects model; pruritus: significant improvement (yes/no); CP participants; parallel‐group design.
7.1
7.1. Analysis
Comparison 7 Cromolyn sodium (CS) versus placebo, Outcome 1 A) Pruritus on VAS scale (0‐10 cm; values from Feily (2012) multiplied by factor 2); UP participants; parallel‐group design.
7.2
7.2. Analysis
Comparison 7 Cromolyn sodium (CS) versus placebo, Outcome 2 A) Subgroup analysis by route of administration; values from Feily (2012) multiplied by factor 2); UP participants; parallel‐group design.
7.3
7.3. Analysis
Comparison 7 Cromolyn sodium (CS) versus placebo, Outcome 3 A) Sensitivity analysis: random‐effects model; values from Feily (2012) multiplied by factor 2; UP participants; parallel‐group design.
7.4
7.4. Analysis
Comparison 7 Cromolyn sodium (CS) versus placebo, Outcome 4 B) Risk for at least one adverse event per participant; UP participants; parallel‐group design.
7.5
7.5. Analysis
Comparison 7 Cromolyn sodium (CS) versus placebo, Outcome 5 B) Subgroup analysis by route of administration; risk for at least one adverse event per participant; UP participants; parallel‐group design.
7.6
7.6. Analysis
Comparison 7 Cromolyn sodium (CS) versus placebo, Outcome 6 B) Sensitivity analysis: random‐effects model; risk for at least one adverse event per participant; UP participants; parallel‐group design.
8.1
8.1. Analysis
Comparison 8 Topical capsaicin versus vehicle, Outcome 1 A) Pruritus on different scales; SMD in UP participants; cross‐over design (Cho: 1. iPTH=<35pg/ml and 2. iPTH>35pg/ml).
8.2
8.2. Analysis
Comparison 8 Topical capsaicin versus vehicle, Outcome 2 A) Subgroup analysis by pruritus scales; SMD; UP participants; cross‐over design (Cho: 1. iPTH=<35pg/ml and 2. iPTH>35pg/ml).
8.3
8.3. Analysis
Comparison 8 Topical capsaicin versus vehicle, Outcome 3 A) Sensitivity analysis: random‐effects model; pruritus on different scales; UP participants; cross‐over design (Cho: 1. iPTH=<35pg/ml and 2. iPTH>35pg/ml).
8.4
8.4. Analysis
Comparison 8 Topical capsaicin versus vehicle, Outcome 4 B) Risk for at least one adverse event per participant; UP participants, cross‐over design.
8.5
8.5. Analysis
Comparison 8 Topical capsaicin versus vehicle, Outcome 5 B) Sensitivity analysis: random‐effects model; risk for at least one adverse event per participant; UP participants; cross‐over design.
9.1
9.1. Analysis
Comparison 9 Zinc sulphate versus placebo, Outcome 1 A) Pruritus on different scales; SMD in UP participants; parallel‐group design.
9.2
9.2. Analysis
Comparison 9 Zinc sulphate versus placebo, Outcome 2 A) Sensitivity analysis: random‐effects model; Pruritus on different scales; SMD in UP participants; parallel‐group design.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Amirkhanlou 2016 {published data only}
    1. Amirkhanlou S, Rashedi A, Taherian J, Hafezi AA, Parsaei S. Comparison of gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients. Pakistan Journal of Medical Sciences 2016; Vol. 32, issue 1:22‐6. - PMC - PubMed
Ashmore 2000 {published data only}
    1. Ashmore SD, Jones CH, Newstead CG, Daly MJ, Chrystyn H. Ondansetron therapy for uremic pruritus in hemodialysis patients. American Journal of Kidney Diseases 2000;35(5):827‐31. - PubMed
Bachs 1989 {published data only}
    1. Bachs L, Parés A, Montserrat E, Piera C, Rodés J. Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet 1989;1(8638):574‐6. - PubMed
Bergasa 2006 {published data only}
    1. Bergasa NV, McGee M, Ginsburg IH, Engler D. Gabapentin in patients with the pruritus of cholestasis: a double‐blind, randomized, placebo‐controlled trial. Hepatology 2006;44(5):1317‐23. - PubMed
Borgeat 1993 {published data only}
    1. Borgeat A, Wilder‐Smith OH, Saiah M, Rifat K. Subhypnotic doses of propofol relieve pruritus induced by epidural and intrathecal morphine. Anesthesiology 1992;76(4):510‐2. - PubMed
Breneman 1992a {published data only}
    1. Breneman DL, Cardone JS, Blumsack RF, Lather RM, Searle EA, Pollack VE. Topical capsaicin for treatment of hemodialysis‐related pruritus. Journal of the American Academy of Dermatology 1992;26(1):91‐4. - PubMed
Cho 1997 {published data only}
    1. Cho YL, Liu HN, Huang TP, Tarng DC. Uremic pruritus: roles of parathyroid hormone and substance P. Journal of the American Academy of Dermatology 1997;36(4):538‐43. - PubMed
De Marchi 1992 {published data only}
    1. Marchi S, Cecchin E, Villalta D, Sepiacci G, Santini G, Bartoli E. Relief of pruritus and decreases in plasma histamine concentrations during erythropoietin therapy in patients with uremia. New England Journal of Medicine 1992;326(15):969‐74. - PubMed
Duncan 1984 {published data only}
    1. Duncan JS, Kennedy HJ, Triger DR. Treatment of pruritus due to chronic obstructive liver disease. Brtish Medical Journal (Clinical Research Edition) 1984;289(6436):22. - PMC - PubMed
Duque 2005 {published data only}
    1. Duque MI, Yosipovitch G, Fleischer AB Jr, Willard J, Freedman BI. Lack of efficacy of tacrolimus ointment 0.1% for treatment of hemodialysis‐related pruritus: a randomized, double‐blind, vehicle‐controlled study. Journal of the American Academy of Dermatology 2005;52:519‐21. - PubMed
Feily 2012 {published data only}
    1. Feily A, Dormanesh B, Ghorbani AR, Moosavi Z, Kouchak M, Cheraghian B, et al. Efficacy of topical cromolyn sodium 4% on pruritus of uremic nephrogenic patients; a randomized double blind study on 60 patients. International Journal of Clinical Pharmacology and Therapeutics 2012;50(7):510‐3. - PubMed
Ghanei 2012 {published data only}
    1. Ghanei E, Zeinali J, Borghei M, Homayouni M. Efficacy of omega‐3 fatty acids supplementation in treatment of uremic pruritus in hemodialysis patients: a double‐blind randomized controlled trial. Iranian Red Crescent Medical Journal 2012;14(9):515–22. - PMC - PubMed
Ghent 1988 {published data only}
    1. Ghent CN, Carruthers SG. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double‐blind, crossover, randomized trial. Gastroenterology 1988;94(2):488‐93. - PubMed
Gunal 2004 {published data only}
    1. Gunal AI, Ozalp G, Yoldas TK, Gunal SY, Kirciman E, Celiker H. Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo‐controlled, double‐blind trial. Nephrology, Dialysis, Transplantation 2004;19(12):3137‐9. - PubMed
Kuiper 2010 {published data only}
    1. Kuiper EM, Erpecum KJ, Beuers U, Hansen BE, Thio HB, Man RA, et al. The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double‐blind, randomized, placebo‐controlled trial. Hepatology 2010;52(4):1334‐40. - PubMed
Kumagai 2010 {published data only}
    1. Kumagai H, Ebata T, Takamori K, Muramatsu T, Nakamoto H, Suzuki H. Effect of a novel kappa‐receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a phase III, randomized, double‐blind, placebo‐controlled study. Nephrology, Dialysis, Transplantation 2010;25(4):1251‐7. - PubMed
Legroux‐Crespel 2004 {published data only}
    1. Legroux‐Crespel E, Clèdes J, Misery L. A comparative study on the effects of naltrexone and loratadine on uremic pruritus. Dermatology 2004;208(4):326‐30. - PubMed
Makhlough 2010 {published data only}
    1. Makhlough A. Topical capsaicin therapy for uremic pruritus in patients on hemodialysis. Iranian Journal of Kidney Diseases 2010;4(2):137‐40. - PubMed
Mapar 2015 {published data only}
    1. Mapar MA, Pazyar N, Siahpoosh A, Latifi SM, Beladi Mousavi SS, Khazanee A. Comparison of the efficacy and safety of zinc sulfate vs. placebo in the treatment of pruritus of hemodialytic patients: a pilot randomized, triple‐blind study. Giornale Italiano di Dermatologia e Venereologia [Official Journal of the Italian Society of Dermatology and Sexually Transmitted Diseases] 2015; Vol. 150, issue 4:351‐5. - PubMed
Mayo 2007 {published data only}
    1. Mayo MJ, Handem I, Saldana S, Jacobe H, Getachew Y, Rush AJ. Sertraline as a first‐line treatment for cholestatic pruritus. Hepatology 2007;45(3):666‐74. - PubMed
Murphy 2003 {published data only}
    1. Murphy M, Reaich D, Pai P, Finn P, Carmichael AJ. A randomized, placebo‐controlled, double‐blind trial of ondansetron in renal itch. British Journal of Dermatology 2003;148(2):314‐7. - PubMed
Naini 2007 {published data only}
    1. Naini AE, Harandi AA, Khanbabapour S, Shahidi S, Seirafiyan S, Mohseni M. Gabapentin: a promising drug for the treatment of uremic pruritus. Saudi Journal of Kidney Diseases and Transplantation 2007;18(3):378‐81. - PubMed
Najafabadi 2012 {published data only}
    1. Najafabadi MM, Faghihi G, Emami A, Monghad M, Moeenzadeh F, Sharif N, et al. Zinc sulfate for relief of pruritus in patients on maintenance hemodialysis. Therapeutic Apheresis & Dialysis 2012;16(2):142‐5. - PubMed
Nakhaee 2015 {published data only}
    1. Nakhaee S, Nasiri A, Waghei Y, Morshedi J. Comparison of Avena sativa, vinegar, and hydroxyzine for uremic pruritus of hemodialysis patients: a crossover randomized clinical trial. Iranian Journal of Kidney Diseases 2015; Vol. 9, issue 4:316‐22. - PubMed
Nasrollahi 2007 {published data only}
    1. Nasrollahi AR, Miladipour A, Ghanei E, Yavari P, Haghverdi F. Montelukast for treatment of refractory pruritus in patients on hemodialysis. Iranian Journal of Kidney Diseases 2007;1(2):73‐7. - PubMed
O'Donohue 2005 {published data only}
    1. O'Donohue JW, Pereira SP, Ashdown AC, Haigh CG, Wilkinson JR, Williams R. A controlled trial of ondansetron in the pruritus of cholestasis. Alimentary Pharmacology & Therapeutics 2005;21(8):1041‐5. - PubMed
Omidian 2013 {published data only}
    1. Omidian, M, Khazanee, A, Yaghoobi, R, Ghorbani, A. R, Pazyar, N, Beladimousavi, S. S, Ghadimi, M, Mohebbipour, A, Feily, A. Therapeutic effect of oral nicotinamide on refractory uremic pruritus: a randomized, double‐blind study. Saudi Journal of Kidney Diseases and Transplantation 2013;24(5):995‐9. - PubMed
Özaykan 2001 {published data only}
    1. Özaykan S, Mansur T, Gündüz S, Güney O. Comparison of ondansetron and cyproheptadine in treatment of uremic pruritus [Üremi Kaşintisi Olan Hastlarda Ondansetron ve Siproheptadinin Etkinliğinin Karşılaştırılması]. Türkderm 2001;35:130‐4.
Pakfetrat 2014 {published data only}
    1. Pakfetrat M, Basiri F, Malekmakan L, Roozbeh J. Effects of turmeric on uremic pruritus in end stage renal disease patients: a double‐blind randomized clinical trial. Journal of Nephrology 2014;27(2):203‐7. - PubMed
Pauli‐Magnus 2000 {published data only}
    1. Pauli‐Magnus C, Mikus G, Alscher DM, Kirschner T, Nagel W, Gugeler N, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, double blind, placebo‐controlled crossover study. Journal of the American Society of Nephrology 2000;11:514‐9. - PubMed
Pederson 1980 {published data only}
    1. Pederson JA, Matter BJ, Czerwinski AW, Llach F. Relief of idiopathic generalized pruritus in dialysis patients treated with activated oral charcoal. Annals of Internal Medicine 1980;93(3):446‐8. - PubMed
Peer 1996 {published data only}
    1. Peer G, Kivity S, Agami O, Fireman E, Silverberg D, Blum M, et al. Randomized cross over trial of naltrexone in uraemic pruritus. Lancet 1996;348(9041):1552‐4. - PubMed
Podesta 1991a {published data only}
    1. Podesta A, Lopez P, Terg R, Villamil F, Flores D, Mastai R, et al. Treatment of pruritus of primary biliary cirrhosis with rifampin. Digestive Diseases and Sciences 1991;36(2):216‐20. - PubMed
Pour‐Reza‐Gholi 2007 {published data only}
    1. Pour‐Reza‐Gholi F, Nasrollahi A, Firouzan A, Nasli Esfahani E, Farrokhi F. Low‐dose doxepin for treatment of pruritus in patients on hemodialysis. Iranian Journal of Kidney Diseases 2007;1(1):34‐7. - PubMed
Shirazian 2013 {published data only}
    1. Shirazian S, Schanler M, Shastry S, Dwivedi S, Kumar M, Rice K, et al. The effect of ergocalciferol on uremic pruritus severity: a randomized controlled trial. Journal of Renal Nutrition 2013;23(4):308‐14. - PubMed
Silva 1994 {published data only}
    1. Silva SR, Viana PC, Lugon NV, Hoette M, Ruzany F, Lugon JR. Thalidomide for the treatment of uremic pruritus: a crossover randomized double‐blind trial. Nephron 1994;67(3):270‐3. - PubMed
Silverberg 1977 {published data only}
    1. Silverberg DS, Iaina A, Reisin E, Rotzak R, Eliahou HE. Cholestyramine in uraemic pruritus. British Medical Journal 1977;1(6063):752‐3. - PMC - PubMed
Smith 1997a {published data only}
    1. Smith KJ, Skelton HG, Yeager J, Lee RB, Wagner KF. Pruritus in HIV‐1 disease: therapy with drugs which may modulate the pattern of immune dysregulation. Dermatology 1997;195(4):353‐8. - PubMed
Tarng 1996 {published data only}
    1. Tarng DC, Cho YL, Liu HN, Huang TP. Hemodialysis‐related pruritus: a double‐blind, placebo‐controlled, crossover study of capsaicin 0.025% cream. Nephron 1996;72(4):617‐22. - PubMed
Terg 2002 {published data only}
    1. Terg R, Coronel E, Sordá J, Muñoz AE, Findor J. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo‐controlled study. Journal of Hepatology 2002;37(6):717‐22. - PubMed
Turner 1994a {published data only}
    1. Turner IB, Rawlins MD, Wood P, James OF. Flumecinol for the treatment of pruritus associated with primary biliary cirrhosis. Alimentary Pharmacology & Therapeutics 1994;8(3):337‐42. - PubMed
Turner 1994b {published data only}
    1. Turner IB, Rawlins MD, Wood P, James OF. Flumecinol for the treatment of pruritus associated with primary biliary cirrhosis. Alimentary Pharmacology & Therapeutics 1994;8(3):337‐42. - PubMed
Vessal 2010 {published data only}
    1. Vessal G, Sagheb MM, Shilian S, Jafari P, Samani SM. Effect of oral cromolyn sodium on CKD‐associated pruritus and serum tryptase level: a double‐blind placebo‐controlled study. Nephrology, Dialysis, Transplantation 2010;25(5):1541‐7. - PubMed
Villamil 2005 {published data only}
    1. Villamil AG, Bandi JC, Galdame OA, Gerona S, Gadano AC. Efficacy of lidocaine in the treatment of pruritus in patients with chronic cholestatic liver diseases. The American Journal of Medicine 2005;118(10):1160‐3. - PubMed
Wikström 2005a {published data only}
    1. Wikström B, Gellert R, Ladefoged SD, Danda Y, Akai M, Ide K, et al. Kappa‐opioid system in uremic pruritus: multicenter, randomized, double‐blind, placebo‐controlled clinical studies. Journal of the American Society of Nephrology 2005;16(12):3742‐7. - PubMed
Wikström 2005b {published data only}
    1. Wikström B, Gellert R, Ladefoged SD, Danda Y, Akai M, Ide K, et al. Kappa‐opioid system in uremic pruritus: multicenter, randomized, double‐blind, placebo‐controlled clinical studies. Journal of the American Society of Nephrology 2005;16(12):3742‐7. - PubMed
Wolfhagen 1997 {published data only}
    1. Wolfhagen FH, Sternieri E, Hop WC, Vitale G, Bertolotti M, Buuren HR. Oral naltrexone treatment for cholestatic pruritus: a double‐blind, placebo‐controlled study. Gastroenterology 1997;113(4):1264‐9. - PubMed
Young 2009 {published data only}
    1. Young TA, Patel TS, Camacho F, Clark A, Freedman BI, Kaur M, et al. A pramoxine‐based anti‐itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients. Journal of Dermatological Treatment 2009;20(2):76‐81. - PubMed
Yue 2015 {published data only}
    1. Yue J, Jiao S, Xiao Y, Ren W, Zhao T, Meng J. Comparison of pregabalin with ondansetron in treatment of uraemic pruritus in dialysis patients: a prospective, randomized, double‐blind study. International Urology and Nephrology 2015; Vol. 47, issue 1:161‐7. - PubMed
Zylicz 2003 {published data only}
    1. Zylicz Z, Krajnik M, Sorge AA, Costantini M. Paroxetine in the treatment of severe non‐dermatological pruritus: a randomized, controlled trial. Journal of Pain and Symptom Management 2003;26(6):1105‐12. - PubMed

References to studies excluded from this review

Almasio 2000 {published data only}
    1. Almasio PL, Floreani A, Chiaramonte M, Provenzano G, Battezzati P, Crosignani A, et al. Multicentre randomized placebo‐controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis. Alimentary Pharmacology & Therapeutics 2000;14(12):1645‐52. - PubMed
Aperis 2010 {published data only}
    1. Aperis G, Paliouras C, Zervos A, Arvanitis A, Alivanis P. The use of pregabalin in the treatment of uraemic pruritus in haemodialysis patients. Journal of Renal Care 2010;36(4):180‐5. - PubMed
Aymard 1980 {published data only}
    1. Aymard JP, Lederlin P, Witz F, Colomb JN, Herbeuval R, Weber B. Cimetidine for pruritus in Hodgkin's disease. British Medical Journal 1980;280(6208):151‐2. - PMC - PubMed
Balaskas 1998 {published data only}
    1. Balaskas EV, Bamihas GI, Karamouzis M, Voyiatzis G, Tourkantonis A. Histamine and serotonin in uremic pruritus: effect of ondansetron in CAPD‐pruritic patients. Nephron 1998;78(4):395‐402. - PubMed
Bergasa 1991 {published data only}
    1. Bergasa NV, Jones EA. Management of the pruritus of cholestasis: potential role of opiate antagonists. American Journal of Gastroenterology 1991;86(10):1404‐12. - PubMed
Bergasa 1992 {published data only}
    1. Bergasa NV, Talbot TL, Alling DW, Schmitt JM, Walker EC, Baker BL, et al. A controlled trial of naloxone infusions for the pruritus of chronic cholestasis. Gastroenterology 1992;102(2):544‐9. - PubMed
Bergasa 1995 {published data only}
    1. Bergasa NV, Alling DW, Talbot TL, Swain MG, Yurdaydin C, Turner ML, et al. Effects of naloxone infusions in patients with the pruritus of cholestasis. A double‐blind, randomized, controlled trial. Annals of Internal Medicine 1995;123(3):161‐7. - PubMed
Bergasa 1999 {published data only}
    1. Bergasa NV, Alling DW, Talbot TL, Wells MC, Jones EA. Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis: a controlled study. Journal of the American Academy of Dermatology 1999;41(3 Pt 1):431‐4. - PubMed
Berman 1998 {published data only}
    1. Berman B, Flores F, Burke G 3rd. Efficacy of pentoxifylline in the treatment of pruritic papular eruption of HIV‐infected persons. Journal of the American Academy of Dermatology 1998;38(6):955‐9. - PubMed
Bigliardi 2007 {published data only}
    1. Bigliardi PL, Stammer H, Jost G, Rufli T, Büchner S, Bigliardi‐Qi M. Treatment of pruritus with topically applied opiate receptor antagonist. Journal of the American Academy of Dermatology 2007;56(6):979‐88. - PubMed
Borgeat 1994 {published data only}
    1. Borgeat A, Mentha G, Savioz D, Wilder‐Smith OH. Pruritus associated with liver disease: Propofol, a new therapeutic approach?. Schweizerische Medizinische Wochenschrift [Swiss Medical Weekly] 1994;124(15):649‐50. - PubMed
Bousquet 1989 {published data only}
    1. Bousquet J, Rivory JP, Maheut M, Michel FB, Mion C. Double‐blind, placebo‐controlled study of nicergoline in the treatment of pruritus in patients receiving maintenance hemodialysis. Journal of Allergy and Clinical Immunology 1989;83(4):825‐8. - PubMed
Breneman 1992b {published data only}
    1. Breneman DL, Cardone JS, Blumsack RF, Lather RM, Searle EA, Pollack VE. Topical capsaicin for treatment of hemodialysis‐related pruritus. Journal of the American Academy of Dermatology 1992;26(1):91‐4. - PubMed
Castello 2011 {published data only}
    1. Castello M, Milani M. Efficacy of topical hydrating and emollient lotion containing 10% urea ISDIN® plus dexpanthenol (Ureadin Rx 10) in the treatment of skin xerosis and pruritus in hemodialyzed patients: an open prospective pilot trial. Giornale Italiano Di Dermatologia e Venereologia [Official Journal of the Italian Society of Dermatology and Sexually Transmitted Diseases] 2011;46(5):321‐5. - PubMed
Chen 2006 {published data only}
    1. Chen YC, Chiu WT, Wu MS. Therapeutic effect of topical gamma‐linolenic acid on refractory uremic pruritus. American Journal of Kidney Diseases 2006;48(1):69‐76. - PubMed
Datta 1966 {published data only}
    1. Datta DV, Sherlock S. Cholestyramine for long term relief of the pruritus complicating intrahepatic cholestasis. Gastroenterology 1966;50(3):323‐32. - PubMed
Davis 2003 {published data only}
    1. Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. Mirtazapine for pruritus. Journal of Pain and Symptom Management 2003;25(3):288‐91. - PubMed
Easton 1978 {published data only}
    1. Easton P, Galbraith PR. Cimetidine treatment of pruritus in polycythemia vera. New England Journal of Medicine 1978;299(20):1134. - PubMed
Fjellner 1979 {published data only}
    1. Fjellner B, Hagermark O. Pruritus in polycythemia vera: treatment with aspirin and possibility of platelet involvement. Acta Dermato‐Venereologica 1979;59(6):505‐12. - PubMed
Ghorbani 2011 {published data only}
    1. Ghorbani AR, Feily A, Khalili A, Dormanesh B. Lack of efficacy of topical calcineurin inhibitor pimecrolimus 1% on pruritus of severely uremic patients: a randomized double‐blind study in 60 patients. Dermatitis 2011;22(3):167‐8. - PubMed
Giovanetti 1995 {published data only}
    1. Giovannetti S, Barsotti G, Cupisti A, Dani L, Bandini S, Angelini D, et al. Oral activated charcoal in patients with uremic pruritus. Nephron 1995;70(2):193‐6. - PubMed
Goicoechea 1999 {published data only}
    1. Goicoechea M, Sequera P, Ochando A, Andrea C, Caramelo C. Uremic pruritus: an unresolved problem in hemodialysis patients. Nephron 1999;82(1):73‐4. - PubMed
Goncalves 2010 {published data only}
    1. Goncalves F. Thalidomide for the control of severe paraneoplastic pruritus associated with Hodgkin's disease. American Journal of Hospice & Palliative Medicine 2010;27(7):486‐7. - PubMed
Hellier 1963 {published data only}
    1. Hellier FF. A comparative trial of trimeprazine and amylobarbitone in pruritus. Lancet 1963;1(7279):471‐2. - PubMed
Jones 2005 {published data only}
    1. Jones EA, Zylicz Z. Treatment of pruritus caused by cholestasis with opioid antagonists. Journal of Palliative Medicine 2005;8(6):1290‐4. - PubMed
Jones 2007 {published data only}
    1. Jones EA, Molenaar HA, Oosting J. Ondansetron and pruritus in chronic liver disease: a controlled study. Hepato‐Gastroenterology 2007;54(76):1196‐9. - PubMed
Juby 1994 {published data only}
    1. Juby LD, Wong VS, Losowsky MS. Buprenorphine and hepatic pruritus. British Journal of Clinical Practice 1994;48(6):331. - PubMed
Kato 2001 {published data only}
    1. Kato A, Takita T, Furuhashi M, Takahashi T, Watanabe T, Maruyama Y, et al. Polymethylmethacrylate efficacy in reduction of renal itching in hemodialysis patients: crossover study and role of tumor necrosis factor‐alpha. Artificial Organs 2001;25(6):441‐7. - PubMed
Korfitis 2008 {published data only}
    1. Korfitis C, Trafalis DT. Carbamazepine can be effective in alleviating tormenting pruritus in patients with hematologic malignancy. Journal of Pain and Symptom Management 2008;35(6):571‐2. - PubMed
Kuypers 2004 {published data only}
    1. Kuypers DR, Claes K, Evenepoel P, Maes B, Vanrenterghem Y. A prospective proof of concept study of the efficacy of tacrolimus ointment on uraemic pruritus (UP) in patients on chronic dialysis therapy. Nephrology, Dialysis, Transplantation 2004;19(7):1895‐901. - PubMed
Lysy 2003 {published data only}
    1. Lysy J, Sistiery‐Ittah M, Israelit Y, Shmueli A, Strauss‐Liviatan N, Mindrul V, et al. Topical capsaicin‐a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study. Gut 2003;52(9):1323‐6. - PMC - PubMed
Mansour‐Ghanaei 2006 {published data only}
    1. Mansour‐Ghanaei F, Taheri A, Froutan H, Ghofrani H, Nasiri‐Toosi M, Bagherzadeh AH, et al. Effect of oral naltrexone on pruritus in cholestatic patients. World Journal of Gastroenterology 2006;12(7):1125‐8. - PMC - PubMed
Marquez 2012 {published data only}
    1. Marquez D, Ramonda C, Lauxmann JE, Romero CA, Vukelic VL, Martinatto C, et al. Uremic pruritus in hemodialysis patients: treatment with desloratidine versus gabapentin. Jornal Brasileiro Nefrologia 2012;34(2):148‐52. - PubMed
Metze 1999a {published data only}
    1. Metze D, Reimann S, Beissert S, Luger T. Efficacy and safety of naltrexone, an oral opiate receptor antagonist, in the treatment of pruritus in internal and dermatological diseases. Journal of the American Academy of Dermatology 1999;41:533‐9. - PubMed
Montero 2006 {published data only}
    1. Montero JL, Pozo JC, Barrera P, Fraga E, Costán G, Domínguez JL, et al. Treatment of refractory cholestatic pruritus with molecular adsorbent recirculating system (MARS). Transplantation Proceedings 2006;38(8):2511‐3. - PubMed
Müller 1998a {published data only}
    1. Müller C, Pongratz S, Pidlich J, Penner E, Kaider A, Schemper M, et al. Treatment of pruritus in chronic liver disease with the 5‐hydroxytryptamine receptor type 3 antagonist ondansetron: a randomized, placebo‐controlled, double‐blind cross‐over trial. European Journal of Gastroenterology & Hepatology 1998;10(10):865‐70. - PubMed
Müller 1998b {published data only}
    1. Müller C, Pongratz S, Pidlich J, Penner E, Kaider A, Schemper M, et al. Treatment of pruritus in chronic liver disease with the 5‐hydroxytryptamine receptor type 3 antagonist ondansetron: a randomized, placebo‐controlled, double‐blind cross‐over trial. European Journal of Gastroenterology & Hepatology 1998;10:865‐70. - PubMed
Podesta 1991b {published data only}
    1. Podesta A, Lopez P, Terg R, Villamil F, Flores D, Mastai R, et al. Treatment of pruritus of primary biliary cirrhosis with rifampin. Digestive Diseases and Sciences 1991;36(2):216‐20. - PubMed
Price 1998 {published data only}
    1. Price TJ, Patterson WK, Olver IN. Rifampicin as treatment for pruritus in malignant cholestasis. Supportive Care in Cancer 1998;6(6):533‐5. - PubMed
Prieto 2004 {published data only}
    1. Prieto LN. The use of midazolam to treat itching in a terminally ill patient with biliary obstruction. Journal of Pain and Symptom Management 2004;28(6):531‐2. - PubMed
Razeghi 2009 {published data only}
    1. Razeghi E, Eskandari D, Ganji MR, Meysamie AP, Togha M, Khashayar P. Gabapentin and uremic pruritus in hemodialysis patients. Renal Failure 2009;31(2):85‐90. - PubMed
Rifai 2006 {published data only}
    1. Rifai K, Hafer C, Rosenau J, Athmann C, Haller H, Peter Manns M, et al. Treatment of severe refractory pruritus with fractionated plasma separation and adsorption (Prometheus ®). Scandinavian Journal of Gastroenterology 2006;41(10):1212‐7. - PubMed
Sja'bani 1997 {published data only}
    1. Sja'bani M, Asdie AH. Effect of erythropoietin on pruritus and quality of life in chronic hemodialyzed end stage renal disease patients. Journal of Clinical Epidemiology 1997;50(Suppl 1):10S.
Ständer 2009 {published data only}
    1. Ständer S, Böckenholt B, Schürmeyer‐Horst F, Weishaupt C, Heuft G, Luger TA, et al. Treatment of chronic pruritus with the selective serotonin re‐uptake inhibitors paroxetine and fluvoxamine: results of an open‐labelled, two‐arm proof‐of‐concept study. Acta Dermato‐Venereologica 2009;89(1):45‐51. - PubMed
Szepietowski 2005 {published data only}
    1. Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerologica Croatica 2005;13(2):97‐103. - PubMed
Tokgöz 2005 {published data only}
    1. Tokgöz B, Ata A, Sİpahİoğlu M, Oymak O, Utaş S, Utaş C. Effects of oral granisetron treatment on uremic pruritus. Turkish Journal of Medical Sciences 2005;35:93‐7.

References to ongoing studies

2005‐003469‐18 {unpublished data only}
    1. 2005‐003469‐18. TRK‐820 UP 5µg [A randomised, double‐blind, placebo‐controlled study of TRK‐820 in haemodyalis patients with uremic pruritus]. clinicaltrialsregister.eu/ctr‐search/trial/2005‐003469‐18/LT 2005‐09‐07.
2009‐010437‐50 {unpublished data only}
    1. 2009‐010437‐50. NA [A Phase 2, randomized, double‐blind, placebo‐controlled study to evaluate the efficacy of different Gabapentin doses in haemodialysis patients with uremic pruritus]. clinicaltrialsregister.eu/ctr‐search/trial/2009‐010437‐50/IT 2009‐03‐27.
ISRCTN13971661 {unpublished data only}
    1. ISRCTN13971661. Balneum Plus cream for the treatment of itchy skin in renal patients. isrctn.com/ISRCTN13971661 2014‐12‐17.
NCT00577967 {unpublished data only}
    1. NCT00577967. Gabapentin ‐ A Solution to Uremic Pruritus? [Gabapentin ‐ A Solution to Uremic Pruritus? A Prospective, Randomized, Placebo‐controlled, Double‐blind Study]. www.clinicaltrials.gov/ct2/show/NCT00577967 2007‐12‐19.
NCT00693654 {unpublished data only}
    1. NCT00693654. Comparative Study of the Efficacy of SARNA Sensitive Lotion for Treatment of Uremic Itch in Adult Hemodialysis Patients [A Controlled Comparative Study of the Efficacy of SARNA Sensitive Lotion for Treatment of Uremic Pruritus in Adult Hemodialysis Patients]. clinicaltrials.gov/ct2/show/NCT00693654 2008‐06‐05.
NCT00793156 {unpublished data only}
    1. NCT00793156. A Randomized‐Withdrawal Phase 3 Study Evaluating the Safety and Efficacy of Oral Nalfurafine HCl (AC‐820)in Subjects on Hemodialysis With Uremic Pruritus (Renal Itch) (AC120‐8231) [A Randomized‐Withdrawal Phase 3 Study Evaluation the Safety and Efficacy of Oral Nalfurafine HCl (AC‐820)in Subjects on Hemodialysis With Uremic Pruritus (Renal Itch)]. clinicaltrials.gov/ct2/show/NCT00793156 2008‐11‐17.
NCT01073501 {unpublished data only}
    1. NCT01073501. Efficacy of Pregabalin in the Management of Chronic Uremic Pruritus. clinicaltrials.gov/ct2/show/NCT01073501 2010‐02‐17.
NCT01513161 {unpublished data only}
    1. NCT01513161. Efficacy and Safety Study of TRK‐820 to Treat Conventional‐treatment‐resistant Pruritus in Patients Receiving Hemodialysis (TRK‐820) [A 14 Day, Multi‐center, Randomized, Double Blinded, Placebo‐controlled, Parallel Group, Fixed Dose, Phase III Clinical Trial to Assess the Efficacy and Safety of TRK‐820 in Treating Conventional‐treatment‐resistant Pruritus in Patients Receiving Hemodialysis]. clinicaltrials.gov/ct2/show/NCT01513161 2010‐11‐23.
NCT01660243 {published data only}
    1. NCT01660243. Efficacy and Safety of MT‐9938 for Treatment of Uremic Pruritus in Subjects With End‐stage Renal Disease Receiving Hemodialysis [A Phase 2, Randomized, Double‐blind, Placebo‐controlled, Fixed‐dose, Parallel‐group, Multicenter, Efficacy, and Safety Study of MT‐9938 for Treatment of Uremic Pruritus in Subjects With End‐stage Renal Disease Receiving Hemodialysis]. clinicaltrials.gov/ct2/show/NCT01660243 2012‐08‐02.
NCT01852318 {unpublished data only}
    1. NCT01852318. Pregabalin for the Treatment of Uremic Pruritus [A Multicenter, Double‐blind, Randomized, Placebo and Active‐controlled Study of Pregabalin for the Treatment of Uremic Pruritus]. clinicaltrials.gov/ct2/show/NCT01852318 2013‐05‐08.
NCT02008864 {unpublished data only}
    1. NCT02008864. Evaluating the Effect of Senna in Uremic Pruritus [Phase II Study of the Effect of Senna Alexandrina Mill. on Uremic Pruritus and Serum IL‐2, INF‐δ and TNF‐α Levels of Hemodialysed Patients]. clinicaltrials.gov/ct2/show/NCT02008864 2013‐12‐01.
NCT02032537 {unpublished data only}
    1. NCT02032537. Efficacy of Calmmax Cream in the Management of Chronic Uremic Pruritus. clinicaltrials.gov/ct2/show/NCT02032537 2014‐01‐06.
NCT02143648 {unpublished data only}
    1. NCT02143648. Study of Nalbuphine HCl ER Tablets in Hemodialysis Patients With Uremic Pruritus [A Randomized, Double‐Blind, Placebo‐Controlled, Parallel, 3‐Arm Study of the Safety and Anti‐Pruritic Efficacy of Nalbuphine HCl ER Tablets in Hemodialysis Patients With Uremic Pruritus]. clinicaltrials.gov/ct2/show/NCT02143648 2014‐05‐17.
NCT02229929 {unpublished data only}
    1. NCT02229929. Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus [A Double‐Blind, Randomized, Placebo‐Controlled Study to Evaluate the Safety and Pharmacokinetics of Intravenous CR845 in Hemodialysis Patients, and Its Safety and Efficacy in Hemodialysis Patients With Uremic Pruritus]. clinicaltrials.gov/ct2/show/NCT02229929 2014‐08‐27.
NCT02696499 {unpublished data only}
    1. NCT02696499. Treatment of Uremic Pruritus With PA101B [Treatment of Uremic Pruritus With Inhaled PA101B in Patients With End‐Stage Renal Disease Requiring Hemodialysis]. clinicaltrials.gov/ct2/show/NCT02696499 2016‐02‐25.
NCT02701166 {unpublished data only}
    1. NCT02701166. The Effect of Bezafibrate on Cholestatic Itch (FITCH) [The Effect of Bezafibrate on Cholestatic Itch]. clinicaltrials.gov/ct2/show/NCT02701166 2016‐03‐02.

Additional references

Ahern 2012
    1. Ahern K, Gilmore ES, Poligone B. Pruritus in cutaneous T‐cell lymphoma: a review. Journal of the American Academy of Dermatology 2012;67(4):760‐8. - PMC - PubMed
Anand 2013
    1. Anand S. Gabapentin for pruritus in palliative care. American Journal of Hospice & Palliative Care 2013;30(2):192‐6. - PubMed
Bergasa 2008
    1. Bergasa NV. Pruritus in primary biliary cirrhosis: pathogenesis and therapy. Clinics in Liver Disease 2008;12(2):385‐406. - PubMed
Bernhard 2005
    1. Bernhard JD. Itch and pruritus: what are they, and how should itches be classified?. Dermatologic Therapy 2005;18:288‐91. - PubMed
Bohlius 2009
    1. Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, et al. Erythropoietin or darbepoetin for patients with cancer‐‐meta‐analysis based on individual patient data. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD007303.pub2] - DOI - PMC - PubMed
Chiang 2011
    1. Chaing HC, Huang V, Cornelius LA. Cancer and itch. Seminars in Cutaneous Medicine and Surgery 2011;30(2):107‐12. - PubMed
Cohen 1988
    1. Cohen J. Statistical Power Analysis for the Behavioral Sciences. United States of America: Erlbaum, 1988.
Derry 2012
    1. Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2012, Issue 9. [DOI: 10.1002/14651858.CD010111] - DOI - PMC - PubMed
Derry 2013
    1. Derry S, Rice ASC, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2013, Issue 2. [DOI: 10.1002/14651858.CD007393.pub3] - DOI - PubMed
Dorman 2010
    1. Dorman S, Perkins P. Droperidol for treatment of nausea and vomiting in palliative care patients. Cochrane Database of Systematic Reviews 2010;10:CD006938. [DOI: 10.1002/14651858.CD006938.pub2] - DOI - PubMed
Duley 2010
    1. Duley L, Gülmezoglu AM, Henderson‐Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre‐eclampsia. Cochrane Database of Systematic Reviews 2010, Issue 11. [DOI: 10.1002/14651858.CD000025.pub2] - DOI - PMC - PubMed
Duo 1987
    1. Duo LJ. Electrical needle therapy of uremic pruritus. Nephron 1987;47(3):179‐83. - PubMed
Elmariah 2011
    1. Elmariah SB, Lerner EA. Topical therapies for pruritus. Seminars in Cutaneous Medicine and Surgery 2011;30(2):118‐26. - PMC - PubMed
Fransway 1988
    1. Fransway AF, Winkelmann RK. Treatment of pruritus. Seminars in Dermatology 1988;7(4):310‐25. - PubMed
Gaudy‐Marqueste 2010
    1. Gaudy‐Marqueste C. Antihistamines. In: Misery L, Ständer S editor(s). Pruritus. London: Springer, 2010:277‐88.
Gooding 2010
    1. Gooding SM, Canter PH, Coelho HF, Boddy K, Ernst E. Systematic review of topical capsaicin in the treatment of pruritus. International Journal of Dermatology 2010;49(8):858‐65. - PubMed
Gowing 2010
    1. Gowing L, Ali R, White JM. Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD002022.pub3] - DOI - PMC - PubMed
GRADE Handbook
    1. Schünemann H, Brożek J, Guyatt G, Oxman A editor(s). GRADE handbook for grading quality of evidence and strength of recommendations (updated October 2013). The GRADE Working Group, 2013. Available from guidelinedevelopment.org/handbook.
GRADEproGDT 2015 [Computer program]
    1. GRADE Working Group, McMaster University. GRADEproGDT. Version accessed prior to 4 October 2016. Hamilton (ON): GRADE Working Group, McMaster University, 2015.
Guyatt 2013a
    1. 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;66:158‐72. - PubMed
Guyatt 2013b
    1. Guyatt GH, Thorlund K, Oxman AD, Walter SD, Patrick D, Furukawa TA, et al. GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles‐continuous outcomes. Journal of Clinical Epidemiology 2013;66:173‐83. - PubMed
Haffenreffer 1660
    1. Haffenreffer S. On pruritus [De pruriti, in Nosodochium, in quo cutis, eique adhaerentium partium, affectus omnes, singulari methodo, et cognoscendi et curandi fidelissime traduntur]. De Pruriti. Ulm: Haffenreffer S, 1660:98‐102.
Hedayati 2005
    1. Hedayati H, Parsons J, Crowther CA. Topically applied anaesthetics for treating perineal pain after childbirth. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD004223.pub2] - DOI - PubMed
Higgins 2002
    1. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in Medicine 2002;21(11):1539‐58. - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org. The Cochrane Collaboration.
Higginson 1997
    1. Higginson IJ, Hearn J. A multicenter evaluation of cancer pain control by palliative care teams. Journal of Pain and Symptom Management 1997;14(1):29‐35. - PubMed
Ikoma 2006
    1. Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M. The neurobiology of itch. Nature Reviews. Neuroscience 2006;7(7):535‐47. - PubMed
Inui 2015
    1. Inui S. Nalfurafine hydrochloride to treat pruritus: a review. Clinical, Cosmetic and Investigational Dermatology 2015;8:249‐55. - PMC - PubMed
Jones 1999
    1. Jones EA, Bergasa NV. The pruritus of cholestasis. Hepatology 1999;29(4):1003‐6. - PubMed
Kantor 1983
    1. Kantor GR, Lookingbill DP. Generalized pruritus and systemic disease. Journal of American Medical Dermatology 1983;9(3):375‐82. - PubMed
Khandelwal 1994
    1. Khandelwal M, Malet PF. Pruritus associated with cholestasis. A review of pathogenesis and management. Digestive Diseases and Sciences 1994;39(1):1‐8. - PubMed
Khurana 2006
    1. Khurana S, Singh P. Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta‐analysis of prospective randomized‐controlled trials. Liver International 2006;26(8):943‐8. - PubMed
Krajnik 2001a
    1. Krajnik M, Zylicz Z. Understanding pruritus in systemic disease. Journal of Pain and Symptom Management 2001;21(2):151‐68. - PubMed
Krajnik 2001b
    1. Krajnik M, Zylicz Z. Pruritus in advanced internal diseases. Pathogenesis and treatment. Netherlands Journal of Medicine 2001;58(1):27‐40. - PubMed
Langner 2009
    1. Langner MD, Maibach HI. Pruritus measurement and treatment. Clinical and Experimental Dermatology 2009;34(3):285‐8. - PubMed
Larijani 1996
    1. Larijani GE, Goldberg ME, Rogers KH. Treatment of opioid‐induced pruritus with ondansetron: report of four patients. Pharmacotherapy 1996;16(5):958‐60. - PubMed
Lober 1988
    1. Lober CW. Should the patient with generalized pruritus be evaluated for malignancy?. Journal of the American Academy of Dermatology 1988;19(2 Pt 1):350‐2. - PubMed
Lowrie 1975
    1. Lowrie EG, Lazarus JM, Hampers CL, Merrill JP. Some statistical methods for use in assessing the adequacy of hemodialysis. Kidney International Supplement 1975;2:231‐42. - PubMed
Manenti 2009
    1. Manenti L, Tansinda P, Vaglio A. Uraemic pruritus: clinical characteristics, pathophysiology and treatment. Drugs 2009;69(3):251‐63. - PubMed
McHugh 1995
    1. McHugh SM, Rifkin IR, Deighton J, Wilson AB, Lachmann PJ, Lockwood CM, et al. The immunosuppressive drug thalidomide induces T helper cell type 2 (Th2) and concomitantly inhibits Th1 cytokine production in mitogen‐ and antigen‐stimulated human peripheral blood mononuclear cell cultures. Clinical & Experimental Immunology 1995;99(2):160‐7. - PMC - PubMed
Mela 2003
    1. Mela M, Mancuso A, Burroughs AK. Review article: pruritus in cholestatic and other liver diseases. Alimentary Pharmacology & Therapeutics 2003;17(7):857–70. - PubMed
Melin 1986
    1. Melin L, Frederikson T, Noren P, Swebilius BG. Behavioural treatment of scratching in patients with atopic dermatitis. British Journal of Dermatology 1986;115(4):467–74. - PubMed
Mettang 1990
    1. Mettang T, Fritz P, Weber J, Machleidt C, Hubl E, Kuhlmann U. Uremic pruritus in patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD): the role of plasma histamine and skin mast cells. Clinical Nephrology 1990;34(3):136‐41. - PubMed
Mettang 2002
    1. Mettang T, Pauli‐Magnus C, Alscher DM. Uraemic pruritus – new perspectives and insights from recent trials. Nephrology, Dialysis, Transplantation 2002;17(9):1558–63. - PubMed
Mettang 2010
    1. Mettang T. Chronic kidney disease‐associated pruritus. In: Misery L, Ständer S editor(s). Pruritus. London: Springer, 2010:167‐77.
Metz 2010
    1. Metz M, Ständer S. Chronic pruritus ‐ pathogenesis, clinical aspects and treatment. Journal of the European Academy of Dermatology and Venereology 2010;24(11):1249‐60. - PubMed
Metze 1999b
    1. Metze D, Reimann S, Luger TA. Effective treatment of pruritus with naltrexone, an orally active opiate antagonist. Annals of the New York Academy of Sciences 1999;885:430‐2. - PubMed
Misery 2010
    1. Misery L, Städer S. Pruritus. London: Springer, 2010.
Moore 2009
    1. 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. [DOI: 10.1002/14651858.CD007076.pub2] - DOI - PMC - PubMed
Moretti 2010
    1. Moretti S, Prignano F, Lotti T. Systemic Immunosuppressants in the treatment of pruritus. In: Misery L, Ständer S editor(s). Pruritus. London: Springer, 2010:307‐10.
Narita 2006
    1. Narita I, Alchi B, Omori K, Sato F, Ajiro J, Saga D, et al. Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients. Kidney International 2006;69(9):1626‐32. - PubMed
Perkins 2009
    1. Perkins P, Dorman S. Haloperidol for the treatment of nausea and vomiting in palliative care patients. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD006271.pub2] - DOI - PubMed
Phan 2010
    1. Phan NQ, Bernhard JD, Luger TA, Ständer S. Antipruritic treatment with systemic μ‐opioid receptor antagonists: a review. Journal of the American Academy of Dermatology 2010;63(4):680‐8. - PubMed
Potter 2003
    1. Potter J, Hami F, Bryan T, Quigley C. Symptoms in 400 patients referred to palliative care services: prevalence and patterns. Palliative Medicine 2003;17(4):310‐4. - PubMed
Proske 2010
    1. Proske S, Hartschuh W. Anal Pruritus. In: Misery L, Ständer S editor(s). Pruritus. 1st Edition. London: Springer, 2010:125‐8.
R Foundation 2015 [Computer program]
    1. The R Foundation. R. Version 3.2.2. The R Foundation, 2015. Available from www.r‐project.org/.
Raap 2012
    1. Raap U, Kapp A, Darsow U. Antidepressant drugs: a reasonable therapy for pruritus?. Der Hautarzt 2012;63(7):553‐7. - PubMed
Ratilal 2005
    1. Ratilal B, Costa J, Sampaio C. Anticonvulsants for preventing seizures in patients with chronic subdural haematoma. Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD004893.pub2] - DOI - PubMed
Reich 2008
    1. Reich A, Heisig M, Szepietowski JC. Visual analogue scale as a validated assessment of pruritus intensity (Abstract OP03; 5th International Workshop for the Study of Itch). Acta Dermato‐Venereologica. 2008:688.
RevMan 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rösner 2010
    1. Rösner S, Hackl‐Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M. Opioid antagonists for alcohol dependence. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD001867.pub3] - DOI - PubMed
Schmelz 1997
    1. Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjork HE. Specific C‐receptors for itch in human skin. Journal of Neuroscience 1997;17(20):8003‐8. - PMC - PubMed
Schwarzer 2015
    1. Schwarzer G, Carpenter JR, Rücker G. Meta‐Analysis with R. Heidelberg: Springer, 2015.
Schworer 1995
    1. Schworer H, Hartmann H, Ramadori G. Relief of cholestatic pruritus by a novel class of drugs: 5‐hydroxytryptamine type 3 (5‐HT3) receptor antagonists: effectiveness of ondansetron. Pain 1995;61(1):33‐7. - PubMed
Seccareccia 2011
    1. Seccareccia D, Gebara N. Pruritus in palliative care. Canadian Family Physician 2011;57(9):1010‐3. - PMC - PubMed
Seiz 1999
    1. Seiz A, Yarbro C. Pruritus. In: Yarbro CH, Frogge M, Goodman M editor(s). Cancer Symptom Management. Boston: Jones and Bartlett, 1999:148‐60.
Sharp 1967
    1. Sharp HL, Carey JBJ, White JG, Krivit W. Cholestyramine therapy in patients with a paucity of intrahepatic bile ducts. Journal of Pediatrics 1967;71(5):723‐36. - PubMed
Siemens 2014
    1. Siemens W, Xander C, Meerpohl JJ, Antes G, Becker G. Drug treatments for pruritus in adult palliative care. Deutsches Ärzteblatt International 2014;111(50):863‐70. - PMC - PubMed
Smith 1997b
    1. Smith PF, Corelli RL. Doxepin in the management of pruritus associated with allergic cutaneous reactions. Annals of Pharmacotherapy 1997;31(5):633‐5. - PubMed
Steinhoff 2006
    1. Steinhoff M, Bienenstock J, Schmelz M, Maurer M, Wei E, Biro T. Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus. Journal of Investigative Dermatology 2006;126(8):1705‐18. - PubMed
Steinhoff 2011
    1. Steinhoff M, Cevikbas F, Ikoma A, Berger TG. Pruritus: management algorithms and experimental therapies. Seminars in Cutaneous Medicine and Surgery 2011;30(2):127‐37. - PMC - PubMed
Stovold 2014
    1. Stovold E, Beecher D, Foxlee R, Noel‐Storr A. Study flow diagrams in Cochrane systematic review updates: an adapted PRISMA flow diagram. Systematic Reviews 2014;3:1‐5. - PMC - PubMed
Ständer 2008
    1. Ständer S, Weisshaar E, Luger TA. Neurophysiological and neurochemical basis of modern pruritus treatment. Experimental Dermatology 2008;17(3):161‐9. - PubMed
Summey 2005
    1. Summey BTJ, Yosipovitch G. Pharmacologic advances in the systemic treatment of itch. Dermatologic Therapy 2005;18(4):328‐32. - PubMed
Summey 2009
    1. Summey B. Pruritus. In: Walsh DT, Caraceni AT, Fainsinger R, et al. editor(s). Palliative Medicine. Philadelphia: Saunders Elsevier, 2009:910‐3.
Suthanthiran 1994
    1. Suthanthiran M, Strom TB. Renal transplantation. New England Journal of Medicine 1994;331(6):365‐76. - PubMed
Szepietowski 2004
    1. Szepietowski JC, Salomon J. Pruritus: still an important clinical problem. Journal of American Academic Dermatology 2004;51(5):842‐3. - PubMed
Tandon 2007
    1. Tandon P, Rowe BH, Vandermeer B, Bain VG. The efficacy and safety of bile acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis‐associated pruritus. American Journal of Gastroenterology 2007;102(7):1528‐36. - PubMed
Tennyson 2001
    1. Tennyson H, Levine N. Neurotropic and psychotropic drugs in dermatology. Dermatologic Clinics 2001;19(1):179‐97. - PubMed
To 2012
    1. To TH, Clark K, Lam L, Shelby‐James T, Currow DC. The role of ondansetron in the management of cholestatic or uremic pruritus‐‐a systematic review. Journal of Pain and Symptom Management 2012;44(5):725‐30. - PubMed
Trauner 2005
    1. Trauner M, Wagner M, Fickert P, Zollner G. Molecular regulation of hepatobiliary transport systems: clinical implications for understanding and treating cholestasis. Journal of Clinical Gastroenterology 2005;39(4 Suppl 2):111‐24. - PubMed
Turk 2008
    1. Turk DC, Dworkin RH, McDermott MP, Bellamy N, Kurke LB, Chandler JM, et al. Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Pain 2008;139(3):485‐93. - PubMed
Turner 1990
    1. Turner IB, James O, Wood P, Ward A, Nagy JT, Kawlins MD. Flumecinol is a powerful inducer of bilirubin conjugation in Gilbert’s syndrome. [Abstract]. Hepatology 1990;12(2):415.
Twycross 2001
    1. Twycross R, Wilcock A. Symptom Management in Advanced Cancer. Oxford: Radcliffe Publishing, 2001.
Twycross 2004
    1. Twycross R. Pruritus: past, present, and future. In: Zylicz Z, Twycross R, Jones EA editor(s). Pruritus in Advanced Disease. Oxford: Oxford University Press, 2004:191‐9.
Ueno 2013
    1. Ueno Y, Mori A, Yanagita T. One year long‐term study on abuse liability of nalfurafine in hemodialysis patients. International Journal of Clinical Pharmacology and Therapeutics 2013;51(11):823‐31. - PubMed
Uthayakumar 1997
    1. Uthayakumar S, Nandwani R, Drinkwater T, Nayagam AT, Darley CR. The prevalence of skin disease in HIV infection and its relationship to the degree of immunosuppression. British Journal of Dermatology 1997;137(4):595‐8. - PubMed
Wallengren 2010
    1. Wallengren J. Measurement of itch. In: Misery L, Ständer S editor(s). Pruritus. London: Springer, 2010:45‐50.
Walsh 2000
    1. Walsh D, Donnelly S, Rybicki L. The symptoms of advanced cancer: relationship to age, gender, and performance status in 1000 patients. Supportive Care in Cancer 2000;8(3):175‐9. - PubMed
Wang 2010
    1. Wang H, Yosipovitch G. New insights into the pathophysiology and treatment of chronic itch in patients with end‐stage renal disease,chronic liver disease, and lymphoma. International Journal of Dermatology 2010;49(1):1‐11. - PMC - PubMed
Watts 2012
    1. Watts K, Chavasse RJ. Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children. Cochrane Database of Systematic Reviews 2012, Issue 5. [DOI: 10.1002/14651858.CD006100.pub2] - DOI - PMC - PubMed
Webster 2005
    1. Webster A, Woodroffe RC, Taylor RS, Chapman JR, Craig JC. Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD003961.pub2] - DOI - PubMed
Wee 2008
    1. Wee B, Hadley G, Derry S. How useful are systematic reviews for informing palliative care practice? Survey of 25 Cochrane systematic reviews. BMC Palliative Care 2008;7:1‐6. - PMC - PubMed
Weisshaar 2003
    1. Weisshaar E, Kucenic MJ, Fleischer AB. Pruritus ‐ a review. Acta Dermato‐Venereologica 2003;213:5‐32. - PubMed
Weisshaar 2009
    1. Weisshaar E, Dalgard F. Epidemilogy of itch: adding the burden of skin morbidity. Acta Dermato‐Venereologica 2009;89:339‐50. - PubMed
Wiffen 2011
    1. Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database of Systematic Reviews 2011, Issue 1. [DOI: 10.1002/14651858.CD005451.pub2] - DOI - PMC - PubMed
Wilde 1996
    1. Wilde MI, Markham A. Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. Drugs 1996;52(5):773‐94. - PubMed
Winkelmann 1964
    1. Winkelmann RK, Müller SA. Pruritus. Annual Review of Medicine 1964;15:53‐64. - PubMed
Winkelmann 1982
    1. Winkelmann RK. Pharmacologic control of pruritus. Medical Clinics of North America 1982;66(5):1119‐33. - PubMed
Yamaguchi 1999
    1. Yamaguchi T, Nagasawa T, Satoh M, Kuraishi Y. Itch‐associated response induced by intradermal serotonin through 5‐HT2 receptors in mice. Neuroscience Research 1999;35(2):77‐83. - PubMed
Yatzidis 1972
    1. Yatzidis H. Activated charcoal rediscovered. British Medical Journal 1972;4(5831):51. - PMC - PubMed
Ye 2001
    1. Ye JH, Ponnudurai R, Schaefer R. Ondansetron: a selective 5‐HT(3) receptor antagonist and its applications in CNS‐related disorders. CNS Drug Review 2001;7(2):199‐213. - PMC - PubMed
Yosipovitch 2003
    1. Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet 2003;361(9358):690‐4. - PubMed
Zylicz 1998
    1. Zylicz Z, Smits C, Krajnik M. Paroxetine for pruritus in advanced cancer. Journal of Pain and Symptom Management 1998;16(2):121‐4. - PubMed
Zylicz 2004
    1. Zylicz Z, Twycross R, Jones AE. Pruritus in Advanced Disease. New York: Oxford University Press, 2004.

References to other published versions of this review

Xander 2013
    1. Xander C, Meerpohl JJ, Galandi D, Buroh S, Schwarzer G, Antes G, et al. Pharmacological interventions for pruritus in adult palliative care patients. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD008320.pub2] - DOI - PubMed

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