Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

CiteScore 2018: 0.85

SCImago Journal Rank (SJR) 2018: 0.494
Source Normalized Impact per Paper (SNIP) 2018: 0.427

See all formats and pricing
More options …
Volume 15, Issue 1


Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy: A nationwide register-based cohort study in Denmark

Jens Søndergaard
  • Research Unit of General Practice, Institute of Public Health, University of Southern Denmark, Odense, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Helene Nordahl Christensen / Rikke Ibsen / Dorte Ejg Jarbøl
  • Research Unit of General Practice, Institute of Public Health, University of Southern Denmark, Odense, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jakob Kjellberg
Published Online: 2017-04-01 | DOI: https://doi.org/10.1016/j.sjpain.2017.01.006


Background and aim

Opioid analgesics are often effective for pain management, but may cause constipation. The aim of this study was to determine healthcare resource use and costs in non-cancer and cancer patients with opioid-induced constipation (OIC).


This was a nationwide register-based cohort study including patients ≥18years of age initiating ≥4 weeks opioid therapy (1998–2012) in Denmark. Ameasure of OIC was constructed based on data from Danish national health registries, and defined as ≥1 diagnosis of constipation, diverticulitis, mega colon, ileus/subileus, abdominal pain/acute abdomen or haemorrhoids and/or ≥2 subsequent prescription issues of laxatives. Total healthcare resource utilization and costs (including pharmacy dispense, inpatient-, outpatient-, emergency room- and primary care) were estimated according to OIC status, opioid treatment dosage and length, gender, age, marital status, and comorbidities using Generalised Linear Model.


We identified 97 169 eligible opioid users (77 568 non-cancer and 19 601 patients with a cancer diagnosis). Among non-cancer patients,15% were classified with OIC,10% had previous constipation, and 75% were without OIC. Patients characteristics of non-cancer OIC patients showed a higher frequency of strong opioid treatment (69% versus 41%), long-term opioid treatment (1189 days versus 584 days), advanced age (73 years versus 61 years), and cardiovascular disease (31%versus 19%) compared to those without OIC (P < 0.001 for all comparisons). Non-cancer patients with OIC had 34% higher total healthcare costs compared to those without OIC (P < 0.001) after adjusting for age, gender, opioid usage, marital status and comorbidities. Among cancer patients, 35% were classified with OIC,14% had previous constipation, and 51% were without OIC. A higher proportion of cancer patients with OIC were continuous opioid users (85% versus 83%) and strong opioid users (97% versus 85%), compared to those without OIC (P <0.001 for both comparisons). Further, the mean number of days on opioids were higher for cancer patients with versus without OIC (329 days versus 238 days, P < 0.001). Total healthcare costs were 25% higher for cancer patients with versus without OIC (P < 0.001) after adjusting for age, gender, opioid usage, marital status and comorbidities.


The results of this nationwide study based on real life data suggested that both non-cancer patients and cancer patients suffering from opioid-induced constipation (OIC) may have higher healthcare resource utilization and higher associated costs compared to those without OIC.


Reducing the number of OIC patients has potential cost savings for the health care system. Special attention should be on patients at potential high risk of OIC, such as strong and long-term opioid treatment, advanced age, and concomitant cardiovascular disease.

This article offers supplementary material which is provided at the end of the article.

Keywords: Opioid-induced constipation; Healthcare costs; Cancer; Non-cancer; Denmark


  • [1]

    Jarlbaek L, Kehlet H, Sjøgren P. [The licit opioid consumption in Denmark]. Ugeskr Laeger 2010;172:3173–8 [in Danish].PubMedGoogle Scholar

  • [2]

    Drewes AM, Munkholm P, Simrén M, Breivik H, Kongsgaard UE, Hatlebakk JG, Agreus L, Friedrichsen M, Christrup LL. Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction—Recommendations of the Nordic Working Group. Scand J Pain 2016;11:111–22.Web of ScienceCrossrefGoogle Scholar

  • [3]

    Boswell K, Kwong WJ, Kavanagh S. Burden of opioid-associated gastrointestinal side effects from clinical and economic perspectives: a systematic literature review. J Opioid Manag 2010;6:269–89.CrossrefPubMedGoogle Scholar

  • [4]

    Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004;112:372–80.CrossrefPubMedGoogle Scholar

  • [5]

    Cook SF, Lanza L, Zhou X, Sweeney CT, Goss D, Hollis K, Mangel AW, Fehnel SE. Gastrointestinal side effects in chronic opioid users: results from a population-based survey. Aliment Pharmacol Ther 2008;27:1224–32.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [6]

    Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med 2009;10:35–42.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [7]

    Hjalte F, Berggren AC, Bergendahl H, Hjortsberg C. The direct and indirect costs of opioid-induced constipation. J Pain Symptom Manage 2010;40:696–703.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [8]

    Bell T, Annunziata K, Leslie JB. Opioid-induced constipation negatively impacts pain management, productivity, and health-related quality of life: findings from the National Health and Wellness Survey. J Opioid Manag 2009;5:137–44.PubMedGoogle Scholar

  • [9]

    Reimer K, Hopp M, Zenz M, Maier C, Holzer P, Mikus G, Bosse B, Smith K, Buschmann-Kramm C, Leyendecker P. Meeting the challenges of opioid-induced constipation in chronic pain management – a novel approach. Pharmacology 2009;83:10–7.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [10]

    Coyne KS, LoCasale RJ, Datto CJ, Sexton CC, Yeomans K, Tack J. Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res 2014;6:269–81.PubMedGoogle Scholar

  • [11]

    Candrilli SD, Davis KL, Iyer S. Impact of constipation on opioid use patterns, health care resource utilization, and costs in cancer patients on opioid therapy. J Pain Palliat Care Pharmacother 2009;23:231–41.PubMedCrossrefGoogle Scholar

  • [12]

    Takemoto ML, Fernandes RA, Almeida GR, Monteiro RD, Colombini-Neto M, Bertola-Neto A. Health care resource use and costs in opioid-treated patients with and without constipation in Brazil. Value Health 2011;14:S78–81.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [13]

    Iyer S, Davis KL, Candrilli S. Opioid use patterns and health care resource utilization in patients prescribed opioid therapy with and without constipation. Manag Care 2010;19:44–51.PubMedGoogle Scholar

  • [14]

    Wan Y, Corman S, Gao X, Liu S, Patel H, Mody R. Economic burden of opioid-induced constipation among long-term opioid users with noncancer pain. Am Health Drug Benefits 2015;8:93–102.PubMedGoogle Scholar

  • [15]

    Kwong WJ, Diels J, Kavanagh S. Costs of gastrointestinal events after outpatient opioid treatment for non-cancer pain. Ann Pharmacother 2010;44:630–40.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [16]

    Pedersen KM, Andersen JS, Sondergaard J. General practice and primary health care in Denmark. J Am Board Fam Med 2012;25:S34–8.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [17]

    Lynge E, Sandegaard JL, Rebolj M. The Danish national patient register. Scand J Public Health 2011;39:30–3.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [18]

    Kildemoes HW, Sorensen HT, Hallas J. The Danish national prescription registry. Scand J Public Health 2011;39:38–41.CrossrefWeb of SciencePubMedGoogle Scholar

  • [19]

    WHO Collaborating Centre for Drug and Statistics Methodology. Guidelines for ATC classification DDD assignment 2013, Oslo; 2012, ISBN 978-82-8082-525-4.Google Scholar

  • [20]

    Buntin MB, Zaslavsky AM. Too much ado about two-part models and transformation? Comparing methods of modeling Medicare expenditures. J Health Econ 2004;23:525–42.PubMedCrossrefGoogle Scholar

  • [21]

    Christensen HN, Olsson U, From J, Breivik H. Opioid-induced constipation, use of laxatives, and health-related quality of life. Scand J Pain 2016;11:104–10.Web of ScienceCrossrefPubMedGoogle Scholar

  • [22]

    Stubhaug A. Advances in understanding and treatment of opioid-induced-bowel-dysfunction, opioid-induced-constipation in particular Nordic recommendations based on multi-specialist input. Scand J Pain 2016;11:163–4.Web of SciencePubMedCrossrefGoogle Scholar

  • [23]

    Gaertner J, Siemens W, Camilleri M, Davies A, Drossman DA, Webster LR, Becker G. Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review. J Clin Gastroenterol 2015;49:9–16.Web of SciencePubMedCrossrefGoogle Scholar

  • [24]

    Camilleri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe GM. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol Motil 2014;26:1386–95.Web of ScienceCrossrefGoogle Scholar

  • [25]

    Kalso E, Allan L, Dellemijn PL, Faura CC, Ilias WK, Jensen TS, Perrot S, Plaghki LH, Zenz M. Recommendations for using opioids in chronic non-cancer pain. Eur J Pain 2003;7:381–6.CrossrefPubMedGoogle Scholar

  • [26]

    Pottegard A, Knudsen TB, van Heesch K, Salmasi H, Schytte-Hansen S, Sondergaard J. Information on risk of constipation for Danish users of opioids, and their laxative use. Int J Clin Pharm 2014;36:291–4.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [27]

    Coyne KS, Margolis MK, Yeomans K, King FR, Chavoshi S, Payne KA, LoCasale RJ. Opioid-Induced Constipation Among Patients with Chronic Noncancer Pain in the United States, Canada, Germany, and the United Kingdom: Laxative Use, Response, and Symptom Burden Over Time. Pain Med 2015;16: 1551–65.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [28]

    Salmoirago-Blotcher E, Crawford S, Jackson E, Ockene J, Ockene I. Constipation and risk of cardiovascular disease among postmenopausal women. Am J Med 2011;124:714–23.Web of ScienceCrossrefPubMedGoogle Scholar

  • [29]

    Olsen J. Who needs selection bias? Scand J Work Environ Health 2014;40:103.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [30]

    Nohr EA, Olsen J. Commentary: epidemiologists have debated representativeness for more than 40 years – has the time come to move on? Int J Epidemiol 2013;42:1016–7.CrossrefPubMedWeb of ScienceGoogle Scholar

About the article

Received: 2016-11-09

Revised: 2017-01-24

Accepted: 2017-01-25

Published Online: 2017-04-01

Published in Print: 2017-04-01

Ethical issues: The study was approved by the Danish Data Protection Agency (No. 2013-54-0414). All data was anonymized, and did not permit identification of individual patients. According to Danish legislation, ethics approval is not required for register-based studies.

Conflicts of interest: J.S. and J.K. have received compensation from AstraZeneca for their work on this report. H.N.C. holds a full time position at AstraZeneca as epidemiologist. The other authors declare that they have no competing interests.

Funding: This work was sponsored by AstraZeneca.

Citation Information: Scandinavian Journal of Pain, Volume 15, Issue 1, Pages 83–90, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1016/j.sjpain.2017.01.006.

Export Citation

© 2017 Scandinavian Association for the Study of Pain.Get Permission

Supplementary Article Materials

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Dilek Yıldırım, Gülbeyaz Can, and Gül Köknel Talu
European Journal of Oncology Nursing, 2019, Volume 41, Page 110
Kordula Lang-Illievich and Helmar Bornemann-Cimenti
The Korean Journal of Pain, 2019, Volume 32, Number 2, Page 69

Comments (0)

Please log in or register to comment.
Log in