Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2017 May 16;5(5):CD012508.
doi: 10.1002/14651858.CD012508.pub2.

Tramadol with or without paracetamol (acetaminophen) for cancer pain

Philip J Wiffen  1 , Sheena Derry  1 , R Andrew Moore  1
Affiliations
Meta-Analysis

Tramadol with or without paracetamol (acetaminophen) for cancer pain

Philip J Wiffen et al. Cochrane Database Syst Rev. .

Abstract

Background: Tramadol is an opioid analgesic licensed for use in moderate to severe pain. It is considered as a low risk for abuse, so control regulations are not as stringent as for 'strong' opioids such as morphine. It has a potential role as a step 2 option of the World Health Organization (WHO) analgesic ladder.

Objectives: To assess the benefits and adverse effects of tramadol with or without paracetamol (acetaminophen) for cancer-related pain.

Search methods: We searched the following databases using a wide range of search terms: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched three clinical trials registry databases. The date of the last search was 2 November 2016.

Selection criteria: We selected studies that were randomised, with placebo or active controls, or both, and included a minimum of 10 participants per treatment arm. We were interested particularly in blinded studies, but also included open studies.We excluded non-randomised studies, studies of experimental pain, case reports, and clinical observations.

Data collection and analysis: Two review authors independently extracted data using a standard form and checked for agreement before entry into Review Manager 5. We included information about the number of participants treated and demographic details, type of cancer, drug and dosing regimen, study design (placebo or active control) and methods, study duration and follow-up, analgesic outcome measures and results, withdrawals, and adverse events. We collated multiple reports of the same study, so that each study, rather than each report, was the unit of interest in the review. We assessed the evidence using GRADE and created a 'Summary of findings' table.The main outcomes of interest for benefit were pain reduction of 30% or greater and 50% or greater from baseline, participants with pain no worse than mild, and participants feeling much improved or very much improved.

Main results: We included 10 studies (12 reports) with 958 adult participants. All the studies enrolled participants with chronic malignant tumour-related pain who were experiencing pain intensities described as moderate to severe, with most experiencing at least 4/10 with current treatment. The mean ages were 59 to 70 years, with participants aged between 24 and 87 years. Study length ranged from one day to six months. Five studies used a cross-over design. Tramadol doses ranged from 50 mg as single dose to 600 mg per day; doses of 300 mg per day to 400 mg per day were most common.Nine studies were at high risk of bias for one to four criteria (only one high risk of bias for size). We judged all the results to be very low quality evidence because of widespread lack of blinding of outcome assessment, inadequately described sequence generation, allocation concealment, and small numbers of participants and events. Important outcomes were poorly reported. There were eight different active comparators and one comparison with placebo. There was little information available for any comparison and no firm conclusions could be drawn for any outcome.Single comparisons of oral tramadol with codeine plus paracetamol, of dihydrocodeine, and of rectal versus oral tramadol provided no data for key outcomes. One study used tramadol combined with paracetamol; four participants received this intervention. One study compared tramadol with flupirtine - a drug that is no longer available. One study compared tramadol with placebo and a combination of cobrotoxin, tramadol, and ibuprofen, but the dosing schedule poorly explained.Two studies (191 participants) compared tramadol with buprenorphine. One study (131 participants) reported a similar proportion of no or mild pain at 14 days.Three studies (300 participants) compared tramadol with morphine. Only one study, combining tramadol, tramadol plus paracetamol, and paracetamol plus codeine as a single weak-opioid group reported results. Weak opioid produced reduction in pain of at least 30% from baseline in 55/117 (47%) participants, compared with 91/110 (82%) participants with morphine. Weak opioid produced reduction in pain of at least 50% in 49/117 (42%) participants, compared with 83/110 (75%) participants with morphine.There was no useful information for any other outcome of benefit or harm.

Authors' conclusions: There is limited, very low quality, evidence from randomised controlled trials that tramadol produced pain relief in some adults with pain due to cancer and no evidence at all for children. There is very low quality evidence that it is not as effective as morphine. This review does not provide a reliable indication of the likely effect. The likelihood that the effect will be substantially different is very high. The place of tramadol in managing cancer pain and its role as step 2 of the WHO analgesic ladder is unclear.

PubMed Disclaimer

Conflict of interest statement

PW: none known.

SD: none known.

RAM has received grant support from Grünenthal relating to individual patient level analyses of trial data regarding tapentadol in osteoarthritis and back pain (2015). He has received honoraria for attending boards with Menarini concerning methods of analgesic trial design (2014), with Novartis (2014) about the design of network meta‐analyses, and RB on understanding pharmacokinetics of drug uptake (2015). He has received honoraria from Omega Pharma (2016) and Futura Pharma (2016) for providing advice on trial and data analysis methods.

This review was identified in a 2019 audit as not meeting the current definition of the Cochrane Commercial Sponsorship policy. At the time of its publication it was compliant with the interpretation of the existing policy. As with all reviews, new and updated, at update this review will be revised according to 2020 policy update.

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.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Bandieri 2016 {published data only}
    1. Bandieri E, Romero M, Ripamonti CI, Artioli F, Sichetti D, Fanizza C, et al. Randomized trial of low‐dose morphine versus weak opioids in moderate cancer pain. Journal of Clinical Oncology 2016;34(5):436‐42. [DOI: 10.1200/JCO.2015.61.0733] - DOI - PubMed
Bono 1997 {published data only}
    1. Bono AV, Cuffari S. Effectiveness and tolerance of tramadol in cancer pain. A comparative study with respect to buprenorphine [Efficacite et tolerance du tramadol dans les douleurs neoplasiques. Etude comparative par rapport a la buprenorphine]. Drugs 1997;53 (Suppl 2):40‐9. [PUBMED: 9190324] - PubMed
Brema 1996 {published data only}
    1. Brema F, Pastorino G, Martini MC, Gottlieb A, Luzzani M, Libretti A, et al. Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial. International Journal of Clinical Pharmacology Research 1996;16(4‐5):109‐16. [PUBMED: 9172009] - PubMed
Leppert 2001 {published data only}
    1. Leppert W. Analgesic efficacy and side effects of oral tramadol and morphine administered orally in the treatment of pain. Nowotwory 2001;51:257‐66.
Leppert 2010 {published data only}
    1. Leppert W, Majkowicz M. The impact of tramadol and dihydrocodeine treatment on quality of life of patients with cancer pain. International Journal of Clinical Practice 2010;64(12):1681‐7. [DOI: 10.1111/j.1742-1241.2010.02422.x] - DOI - PubMed
Luben 1994 {published data only}
    1. Luben V, Muller H, Lobisch M, Worz R. Treatment of tumor pain with flupirtine. Results of a double‐blind study versus tramadol. Fortschritte der Medizin 1994;112(19):282‐6. [PUBMED: 7927099] - PubMed
Mercadante 2005 {published data only}
    1. Mercadante S, Arcuri E, Fusco F, Tirelli W, Villari P, Bussolino C, et al. Randomized double‐blind, double‐dummy crossover clinical trial of oral tramadol versus rectal tramadol administration in opioid‐naive cancer patients with pain. Supportive Care in Cancer 2005;13(9):702‐7. [DOI: 10.1007/s00520-004-0760-9] - DOI - PubMed
Rodriguez 2007 {published data only}
    1. Rodriguez RF, Bravo LE, Castro F, Montoya O, Castillo JM, Castillo MP, et al. Incidence of weak opioids adverse events in the management of cancer pain: a double‐blind comparative trial. Journal of Palliative Medicine 2007;10(1):56‐60. [DOI: 10.1089/jpm.2006.0117] - DOI - PubMed
    1. Rodriguez RF, Castillo JM, Castillo MP, Montoya O, Daza P, Rodriguez MF, et al. Hydrocodone/acetaminophen and tramadol chlorhydrate combination tablets for the management of chronic cancer pain: a double‐blind comparative trial. [Erratum appears in Clinical Journal of Pain 2008;24(7):649]. Clinical Journal of Pain 2008;24(1):1‐4. [DOI: 10.1097/AJP.0b013e318156ca4d] - DOI - PubMed
Wilder‐Smith 1994 {published data only}
    1. Wilder‐Smith CH, Schimke J, Osterwalder B, Senn HJ. Oral tramadol, a mu‐opioid agonist and monoamine reuptake‐blocker, and morphine for strong cancer‐related pain. Annals of Oncology 1994;5(2):141‐6. [PUBMED: 8186157] - PubMed
Xu 2006 {published data only}
    1. Xu JM, Song ST, Feng FY, Huang FL, Yang Y, Xie GR, et al. Cobrotoxin‐containing analgesic compound to treat chronic moderate to severe cancer pain: results from a randomized, double‐blind, cross‐over study and from an open‐label study. Oncology Reports 2006;16(5):1077‐84. [DOI: 10.3892/or.16.5.1077] - DOI - PubMed

References to studies excluded from this review

Arbaiza 2007 {published data only}
    1. Arbaiza D, Vidal O. Tramadol in the treatment of neuropathic cancer pain: a double‐blind, placebo‐controlled study. Clinical Drug Investigation 2007;27(1):75‐83. [DOI: 10.2165/00044011-200727010-00007] - DOI - PubMed
Marinangeli 2007 {published data only}
    1. Marinangeli F, Ciccozzi A, Aloisio L, Colangeli A, Paladini A, Bajocco C, et al. Improved cancer pain treatment using combined fentanyl‐TTS and tramadol. Pain Practice 2007;7(4):307‐12. [DOI: 10.1111/j.1533-2500.2007.00155.x] - DOI - PubMed
Tassinari 2011 {published data only}
    1. Tassinari D, Drudi F, Rosati M, Tombesi P, Sartori S, Maltoni M. The second step of the analgesic ladder and oral tramadol in the treatment of mild to moderate cancer pain: a systematic review. Palliative Medicine 2011;25(5):410‐23. [DOI: 10.1177/0269216311405090] - DOI - PubMed
Yavuz 2004 {published data only}
    1. Yavuz L, Eroglu F, Ozsoy M. The efficacy of intravenous versus epidural tramadol with patient‐controlled analgesia (PCA) in gynecologic cancer pain. European Journal of Gynaecological Oncology 2004;25(2):215‐8. [PUBMED: 15032285] - PubMed

Additional references

AlBalawi 2013
    1. AlBalawi Z, McAlister FA, Thorlund K, Wong M, Wetterslev J. Random error in cardiovascular meta‐analyses: how common are false positive and false negative results?. International Journal of Cardiology 2013;168(2):1102‐7. [DOI: 10.1016/j.ijcard.2012.11.048] - DOI - PubMed
Bao 2016
    1. Bao YJ, Hou W, Kong XY, Yang L, Xia J, Hua BJ, et al. Hydromorphone for cancer pain. Cochrane Database of Systematic Reviews 2016, Issue 10. [DOI: 10.1002/14651858.CD011108.pub2] - DOI - PMC - PubMed
Beakley 2015
    1. Beakley BD, Kaye AM, Kaye AD. Tramadol, pharmacology, side effects, and serotonin syndrome: a review. Pain Physician 2015;18(4):395‐400. [PUBMED: 26218943] - PubMed
Bozkurt 2005
    1. Bozkurt P. Use of tramadol in children. Paediatric Anaesthesia 2005;15(12):1041‐7. [DOI: 10.1111/j.1460-9592.2005.01738.x] - DOI - PubMed
Breivik 2009
    1. Breivik H, Cherny N, Collett B, Conno F, Filbet M, Foubert AJ, et al. Cancer‐related pain: a pan‐European survey of prevalence, treatment, and patient attitudes. Annals of Oncology 2009;20(8):1420‐33. [DOI: 10.1093/annonc/mdp001] - DOI - PubMed
Cancer Research UK 2016
    1. Cancer Research UK. Cancer statistics for the UK. www.cancerresearchuk.org/health‐professional/cancer‐statistics (accessed 21 November 2016).
Cepeda 2006
    1. Cepeda MS, Camargo F, Zea C, Velencia L. Tramadol for osteoarthritis. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD005522.pub2] - DOI - PubMed
Dechartres 2013
    1. 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] - DOI - PMC - PubMed
Dechartres 2014
    1. Dechartres A, Altman DG, Trinquart L, Boutron I, Ravaud P. Association between analytic strategy and estimates of treatment outcomes in meta‐analyses. JAMA 2014;312:623‐30. [DOI: 10.1001/jama.2014.8166] - DOI - PubMed
Deng 2012
    1. Deng D, Fu L, Zhao YX, Wu X, Zhang G, Liang C, et al. The relationship between cancer pain and quality of life in patients newly admitted to Wuhan Hospice Center of China. American Journal of Hospital Palliative Care 2012;29(1):53‐9. [DOI: 10.1177/1049909111418636] - DOI - PubMed
Dreidi 2016
    1. Dreidi MM, Hamdan‐Mansour AM. Pain, sleep disturbance, and quality of life among Palestinian patients diagnosed with cancer. Journal of Cancer Education 2016;31(4):796‐803. [DOI: 10.1007/s13187-015-0946-5] - DOI - PubMed
Dworkin 2008
    1. 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] - DOI - PubMed
Edwards 2002
    1. Edwards JE, McQuay HJ, Moore RA. Combination analgesic efficacy: individual patient data meta‐analysis of single‐dose oral tramadol plus acetaminophen in acute postoperative pain. Journal of Pain and Symptom Management 2002;23(2):121‐30. [DOI: 10.1016/S0885-3924(01)00404-3] - DOI - PubMed
EMA 2013
    1. European Medicines Agency. Flupirtine‐containing medicines. www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Flu... (accessed 24 January 2017).
EPOC 2015
    1. Effective Practice, Organisation of Care (EPOC). 23. Worksheets for preparing a Summary of Findings using GRADE. Resources for review authors, 2015. epoc.cochrane.org/epoc‐specific‐resources‐review‐authors (accessed 30 November 2016).
Fanelli 2017
    1. Fanelli D, Costas R, Ioannidis JP. Meta‐assessment of bias in science. Proceedings of the National Academy of Sciences of the United States of America 2017;114(14):3714‐9. [DOI: 10.1073/pnas.1618569114] - DOI - PMC - PubMed
Gan 2007
    1. Gan SH, Ismail R, Wan Adnan WA, Zulmi W. Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Molecular Diagnosis and Therapy 2007;11(3):171‐81. [DOI: 10.1007/BF03256239] - DOI - PubMed
Grond 2004
    1. Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clinical Pharmacokinetics 2004;43(13):879‐932. [DOI: 10.2165/00003088-200443130-00004] - DOI - PubMed
Guyatt 2011
    1. 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] - DOI - PubMed
Guyatt 2013a
    1. 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;66:151‐7. [DOI: 10.1016/j.jclinepi.2012.01.006] - DOI - PubMed
Guyatt 2013b
    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. [DOI: 10.1016/j.jclinepi.2012.01.012] - DOI - PubMed
Hadley 2013
    1. Hadley G, Derry S, Moore RA, Wiffen PJ. Transdermal fentanyl for cancer pain. Cochrane Database of Systematic Reviews 2013, Issue 10. [DOI: 10.1002/14651858.CD010270.pub2] - DOI - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Hollingshead 2006
    1. Hollingshead J, Dühmke RM, Cornblath DR. Tramadol for neuropathic pain. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD003726.pub3] - DOI - PubMed
IARC 2012
    1. International Agency for Research on Cancer. GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. globocan.iarc.fr/Pages/fact_sheets_cancer.aspx (accessed 21 November 2016).
L'Abbé 1987
    1. L'Abbé KA, Detsky AS, O'Rourke K. Meta‐analysis in clinical research. Annals of Internal Medicine 1987;107(2):224‐33. [DOI: 10.7326/0003-4819-107-2-224] - DOI - PubMed
Lintz 1998
    1. Lintz W, Barth H, Osterloh G, Schmidt‐Bothelt E. Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 3rd Communication: suppositories. Arzneimittel‐Forschung 1998;48(9):889‐99. [PUBMED: 9793614] - PubMed
Martindale 2016
    1. Brayfield A, editor. Tramadol hydrochloride. Martindale ‐ the complete drug reference (available at medicinescomplete.com) (accessed 21 November 2016). 8th Edition. London: Pharmaceutical Press, 2016.
McQuay 1998
    1. McQuay H, Moore A. An Evidence‐based Resource for Pain Relief. Oxford: Oxford University Press, 1998. [ISBN: 0‐19‐263048‐2]
Mikan 2016
    1. Mikan F, Wada M, Yamada M, Takahashi A, Onishi H, Ishida M, et al. The association between pain and quality of life for patients with cancer in an outpatient clinic, an inpatient oncology ward, and inpatient palliative care units. American Journal of Hospital Palliative Care 2016;33(8):782‐90. [DOI: 10.1177/1049909116630266] - DOI - PubMed
Minami 2015
    1. Minami K, Ogata J, Uezono Y. What is the main mechanism of tramadol?. Naunyn‐Schmiedebergs Archiv fur Pharmakologie 2015;388:999‐1007. [DOI: 10.1007/s00210-015-1167-5] - DOI - PubMed
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, the PRISMA Group. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Medicine 2009;6(7):e1000097. [DOI: 10.1371/journal.pmed.1000097] - DOI - PMC - PubMed
Moore 1997
    1. Moore RA, McQuay HJ. Single‐patient data meta‐analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Pain 1997;69(3):287‐94. [DOI: 10.1016/S0304-3959(96)03291-5] - DOI - PubMed
Moore 1998
    1. 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] - DOI - PubMed
Moore 2008
    1. Moore RA, Barden J, Derry S, McQuay HJ. Managing potential publication bias. In: McQuay HJ, Kalso E, Moore RA editor(s). Systematic Reviews in Pain Research: Methodology Refined. Seattle: IASP Press, 2008:15‐24. [ISBN: 978–0–931092–69–5]
Moore 2010
    1. Moore RA, Moore OA, Derry S, Peloso PM, Gammaitoni AR, Wang H. Responder analysis for pain relief and numbers needed to treat in a meta‐analysis of etoricoxib osteoarthritis trials: bridging a gap between clinical trials and clinical practice. Annals of the Rheumatic Diseases 2010;69(2):374‐9. [DOI: 10.1136/ard.2009.107805] - DOI - PMC - PubMed
Moore 2013
    1. 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] - DOI - PubMed
Nguyen 2017
    1. Nguyen TL, Collins GS, Lamy A, Devereaux PJ, Daurès JP, Landais P, et al. Simple randomization did not protect against bias in smaller trials. Journal of Clinical Epidemiology 2017;S0895‐4356(16):30344‐4. [DOI: 10.1016/j.jclinepi.2017.02.010] - DOI - PubMed
NICE 2016
    1. National Institute for Health and Care Excellence. Palliative cancer care ‐ pain, 2016. cks.nice.org.uk/palliative‐cancer‐care‐pain (accessed 2 February 2017).
Nicholson 2017
    1. Nicholson AB, Watson GR, Derry S, Wiffen PJ. Methadone for cancer pain. Cochrane Database of Systematic Reviews 2017, Issue 2. [DOI: 10.1002/14651858.CD003971.pub4] - DOI - PMC - PubMed
Nüesch 2010
    1. 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] - DOI - PMC - PubMed
PaPaS 2012
    1. Cochrane Pain, Palliative and Supportive Care Group. PaPaS author and referee guidance. papas.cochrane.org/papas‐documents (accessed 21 November 2016).
Pedersen 2005
    1. Pedersen RS, Damkier P, Brosen K. Tramadol as a new probe for cytochrome P450 2D6 phenotyping: a population study. Clinical Pharmacology and Therapeutics 2005;77(6):458‐67. [DOI: 10.1016/j.clpt.2005.01.014] - DOI - PubMed
Portenoy 1999
    1. Portenoy RK, Lesage P. Management of cancer pain. Lancet 1999;353(9165):1695‐700. [DOI: 10.1016/S0140-6736(99)01310-0] - DOI - PubMed
Prommer 2015
    1. Prommer EE. Pharmacological management of cancer‐related pain. Cancer Control 2015;22(4):412‐25. [PUBMED: 26678968] - PubMed
Radbruch 2013
    1. Radbruch L, Glaeske G, Grond S, Münchberg F, Scherbaum N, Storz E, et al. Topical review on the abuse and misuse potential of tramadol and tilidine in Germany. Substance Abuse 2013;34(3):313‐20. [DOI: 10.1080/08897077.2012.735216] - DOI - PubMed
Reeves 2008
    1. Reeves RR, Burke RS. Tramadol: basic pharmacology and emerging concepts. Drugs of Today (Barcelona, Spain : 1998) 2008;44(11):827‐36. [DOI: 10.1358/dot.2008.44.11.1289441] - DOI - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Schmidt‐Hansen 2015a
    1. Schmidt‐Hansen M, Bromham N, Taubert M, Arnold S, Hilgart JS. Buprenorphine for treating cancer pain. Cochrane Database of Systematic Reviews 2015, Issue 3. [DOI: 10.1002/14651858.CD009596.pub4] - DOI - PMC - PubMed
Schmidt‐Hansen 2015b
    1. Schmidt‐Hansen M, Bennett MI, Arnold S, Bromham N, Hilgart JS. Oxycodone for cancer‐related pain. Cochrane Database of Systematic Reviews 2015, Issue 2. [DOI: 10.1002/14651858.CD003870.pub5] - DOI - PubMed
Scott 2000
    1. Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs 2000;60(1):139‐76. [DOI: 10.2165/00003495-200060010-00008] - DOI - PubMed
Straube 2014
    1. Straube C, Derry S, Jackson KC, Wiffen PJ, Bell RF, Strassels S, et al. Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database of Systematic Reviews 2014, Issue 9. [DOI: 10.1002/14651858.CD006601.pub4] - DOI - PMC - PubMed
Thorlund 2011
    1. Thorlund K, Imberger G, Walsh M, Chu R, Gluud C, Wetterslev J, et al. The number of patients and events required to limit the risk of overestimation of intervention effects in meta‐analysis ‐ a simulation study. PLoS One 2011;6(10):e25491. [DOI: 10.1371/journal.pone.0025491] - DOI - PMC - PubMed
Turner 2013
    1. Turner RM, Bird SM, Higgins JP. The impact of study size on meta‐analyses: examination of underpowered studies in Cochrane reviews. PLoS One 2013;8(3):e59202. [DOI: 10.1371/journal.pone.0059202] - DOI - PMC - PubMed
Twycross 2014
    1. Twycross R, Wilcock A, Howard P. Palliative Care Formulary. Nottingham: Palliativedrugs.com Ltd, 2014.
van den Beuken‐van Everdingen 2016
    1. Beuken‐van Everdingen MH, Hochstenbach LM, Joosten EA, Tjan‐HeijnenVC, Janssen DJ. Update on prevalence of pain in patients with cancer: systematic review and meta‐analysis. Journal of Pain and Symptom Management 2016;51:1070‐90. [DOI: 10.1016/j.jpainsymman.2015.12.340] - DOI - PubMed
WHO 2016
    1. World Health Organization. WHO analgesic ladder. www.who.int/cancer/palliative/painladder/en/ (accessed 21 November 2016).
Wiffen 2013
    1. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database of Systematic Reviews 2013, Issue 7. [DOI: 10.1002/14651858.CD003868.pub3] - DOI - PubMed
Wiffen 2014
    1. Wiffen PJ, Derry S, Moore RA. Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain. Cochrane Database of Systematic Reviews 2014, Issue 5. [DOI: 10.1002/14651858.CD011056.pub2] - DOI - PMC - PubMed
Wiffen 2015
    1. Wiffen PJ, Derry S, Naessens K, Bell RF. Oral tapentadol for cancer pain. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD011460.pub2] - DOI - PMC - PubMed
Wiffen 2016
    1. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database of Systematic Reviews 2016, Issue 4. [DOI: 10.1002/14651858.CD003868.pub4] - DOI - PMC - PubMed

LinkOut - more resources