Skip to main content
Log in

Pharmacoeconomic Impact of Adverse Events of Long-Term Opioid Treatment for the Management of Persistent Pain

  • Review Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Opioids are the most powerful analgesic drugs currently available and consequently form an essential part of the treatment options for malignant and non-malignant chronic pain. However, the benefits of these medications can be offset by gastrointestinal adverse events such as nausea, vomiting and constipation, as well as adverse events affecting the CNS. These occur relatively frequently in patients receiving long-term opioids for pain relief and are a cause of additional patient suffering and reduced work and social functioning, measured as reductions in quality-of-life outcomes. Consequently, adverse events are often the cause of treatment non-compliance or discontinuation (non-persistence). A literature search was conducted using BIOSIS Previews, EMBASE, Cochrane Collaboration and MEDLINE databases to identify references with specific relevance to the measurement of health outcomes related to adverse events of long-term opioid treatment of chronic pain. The results of this search highlighted that clinical interventions required to manage adverse events associated with opioids, and to provide alternative methods of pain control, both incur direct costs. These are largely driven by the cost of medical consults and drug supplies. Indirect costs are generated from work absences and reduced social functioning. Estimated preference ratings, providing an insight into the trade-off between effective pain control and adverse events, have shown that utility decrements associated with an increase in adverse-event severity were similar in size to those caused by a shift from well controlled to poorly controlled pain. Given the rising prevalence of chronic pain conditions (affecting one in five adult Europeans), the direct and indirect costs incurred from the management of adverse events with longterm opioids are likely to be multiplied, contributing to the socioeconomic burden of chronic pain. For this reason, the adverse-event profile of opioid-based analgesics should be improved to achieve more efficient long-term pain control.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II

Similar content being viewed by others

References

  1. Breivik H, Collett B, Ventafridda V, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 2006 May; 10(4): 287–333

    Article  PubMed  Google Scholar 

  2. Catala E, Reig E, Artes M, et al. Prevalence of pain in the Spanish population: telephone survey in 5000 homes. Eur J Pain 2002; 6(2): 133–40

    Article  PubMed  CAS  Google Scholar 

  3. The Patients Association. Pain in older people: the carer’s perspective. Summary report 2006 [online]. Available from URL: http://www.patients-association.org.uk/Research-Publications/89 [Accessed 2010 Nov 1]

  4. Schmier JK, Palmer CS, Flood EM, et al. Utility assessments of opioid treatment for chronic pain. Pain Med 2002 Sep;3(3): 218–30

    Article  PubMed  Google Scholar 

  5. Becker N, Bondegaard Thomsen A, Olsen AK, et al. Pain epidemiology and health related quality of life in chronic non-malignant pain patients referred to a Danish multi-disciplinary pain center. Pain 1997 Dec; 73(3): 393–400

    Article  PubMed  CAS  Google Scholar 

  6. Hansson PT. Neuropathic pain: definition, epidemiology, classification and diagnostic work-up. In: Justins D, editor. Pain 2005 — an updated review: refresher course syllabus. Seattle (WA): IASP Press®, 2005: 91–5

    Google Scholar 

  7. Zech DF, Grond S, Lynch J, et al. Validation of World Health Organization guidelines for cancer pain relief: a 10-year prospective study. Pain 1995 Oct; 63(1): 65–76

    Article  PubMed  CAS  Google Scholar 

  8. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, et al. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol 2007 Sep; 18(9): 1437–49

    Article  PubMed  Google Scholar 

  9. Katz WA. Musculoskeletal pain and its socioeconomic implications. Clin Rheumatol 2002 Feb; 21Suppl. 1: S2–4

    Article  PubMed  Google Scholar 

  10. McNicol E. Opioid side effects. Pain: Clinical Updates 2007; 15(2): 1–6

    Google Scholar 

  11. Portenoy RK, Farrar JT, Backonja MM, et al. Long-term use of controlled-release oxycodone for noncancer pain: results of a 3-year registry study. Clin J Pain 2007 May; 23(4): 287–99

    Article  PubMed  Google Scholar 

  12. Bell RF, Wisloff T, Eccleston C, et al. Controlled clinical trials in cancer pain: how controlled should they be? A qualitative systematic review. Br J Cancer 2006 Jun 5; 94(11): 1559–67

    PubMed  CAS  Google Scholar 

  13. McNicol E, Horowicz-Mehler N, Fisk RA, et al. Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review. J Pain 2003 Jun; 4(5): 231–56

    Article  PubMed  Google Scholar 

  14. Kalso E, Allan L, Dellemijn PL, et al. Recommendations for using opioids in chronic non-cancer pain. Eur J Pain 2003; 7(5): 381–6

    Article  PubMed  CAS  Google Scholar 

  15. McQuay H. Opioids in pain management. Lancet 1999 Jun 26; 353(9171): 2229–32

    Article  PubMed  CAS  Google Scholar 

  16. World Health Organization. Cancer pain relief with a guide to opioid availability. 2nd ed. Geneva: World Health Organization, 1996

    Google Scholar 

  17. Rowbotham MC, Lindsey CD. How effective is long-term opioid therapy for chronic noncancer pain? Clin J Pain 2007 May; 23(4): 300–2

    Article  PubMed  Google Scholar 

  18. Moore RA, McQuay HJ. Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids. Arthritis Res Ther 2005; 7(5): R1046–51

    Article  PubMed  CAS  Google Scholar 

  19. Kalso E, Edwards JE, Moore RA, et al. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004 Dec; 112(3): 372–80

    Article  PubMed  CAS  Google Scholar 

  20. McDermott AM, Toelle TR, Rowbotham DJ, et al. The burden of neuropathic pain: results from a cross-sectional survey. Eur J Pain 2006 Feb; 10(2): 127–35

    Article  PubMed  Google Scholar 

  21. Quigley C. Opioid switching to improve pain relief and drug tolerability. Cochrane Database Syst Rev 2004; (3): CD004847

  22. Noble M, Treadwell JR, Tregear SJ, et al. Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev 2007; (3): CD006605

  23. Dennison C, Prasad M, Lloyd A, et al. The health-related quality of life and economic burden of constipation. Pharma-coeconomics 2005; 23(5): 461–76

    Article  Google Scholar 

  24. Weiss SC, Emanuel LL, Fairclough DL, et al. Understanding the experience of pain in terminally ill patients. Lancet 2001 Apr 28; 357(9265): 1311–5

    Article  PubMed  CAS  Google Scholar 

  25. Neighbors DM, Bell TJ, Wilson J, et al. Economic evaluation of the fentanyl transdermal system for the treatment of chronic moderate to severe pain. J Pain Symptom Manage 2001 Feb; 21(2): 129–43

    Article  PubMed  CAS  Google Scholar 

  26. Greiner W, Lehmann K, Earnshaw S, et al. Economic evaluation of Durogesic in moderate to severe, nonmalignant, chronic pain in Germany. Eur J Health Econ 2006 Dec; 7(4): 290–6

    Article  PubMed  CAS  Google Scholar 

  27. Guest JF, Hart WM, Cookson RF. Cost analysis of palliative care for terminally ill cancer patients in the UK after switching from weak to strong opioids. Palliative Care Advisory Committee. Pharmacoeconomics 1998 Sep; 14(3): 285–97

    CAS  Google Scholar 

  28. Dellemijn PL, van Duijn H, Vanneste JA. Prolonged treatment with transdermal fentanyl in neuropathic pain. J Pain Symptom Manage 1998 Oct; 16(4): 220–9

    Article  PubMed  CAS  Google Scholar 

  29. Lehmann K, Radbruch L, Gockel HH, et al. Costs of opioid therapy for chronic nonmalignant pain in Germany: an economic model comparing transdermal fentanyl (Durogesic) with controlled-release morphine. Eur J Health Econ 2002; 3(2): 111–9

    Article  Google Scholar 

  30. Villars P, Dodd M, West C, et al. Differences in the prevalence and severity of side effects based on type of analgesic prescription in patients with chronic cancer pain. J Pain Symptom Manage 2007 Jan; 33(1): 67–77

    Article  PubMed  Google Scholar 

  31. Frei A, Andersen S, Hole P, et al. A one year health economic model comparing transdermal fentanyl with sustained-release morphine in the treatment of chronic noncancer pain. J Pain Palliat Care Pharmacother 2003; 17(2): 5–26

    Article  PubMed  Google Scholar 

  32. Liedgens H, Nuijten MJ, Nautrup BP. Economic evaluation of tramadol/paracetamol combination tablets for osteoarthritis pain in the Netherlands. Clin Drug Investig 2005; 25(12): 785–802

    Article  PubMed  CAS  Google Scholar 

  33. Aparasu R, McCoy RA, Weber C, et al. Opioid-induced emesis among hospitalized nonsurgical patients: effect on pain and quality of life. J Pain Symptom Manage 1999 Oct; 18(4): 280–8

    Article  PubMed  CAS  Google Scholar 

  34. Bell T, Milanova T, Grove G, et al. Prevalence, severity and impact of opioid-induced GI side effects in the EU: results of a patient survey. Eur J Pain 2006; 10Suppl. 1: S173

    Google Scholar 

  35. Palos GR, Mendoza TR, Cantor SB, et al. Perceptions of analgesic use and side effects: what the public values in pain management. J Pain Symptom Manage 2004 Nov; 28(5): 460–73

    Article  PubMed  Google Scholar 

  36. Ahmedzai S, Brooks D. Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group. J Pain Symptom Manage 1997 May; 13(5): 254–61

    Article  PubMed  CAS  Google Scholar 

  37. Chou R, Clark E, Helfand M. Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. J Pain Symptom Manage 2003 Nov; 26(5): 1026–48

    Article  PubMed  CAS  Google Scholar 

  38. Frank L, Schmier J, Kleinman L, et al. Time and economic cost of constipation care in nursing homes. J Am Med Dir Assoc 2002 Jul–Aug; 3(4): 215–23

    Article  PubMed  Google Scholar 

  39. Sabatowski R, Tark M, Frank L, et al. Effect of alvimopan on health-related quality of life (HRQOL) in subjects with opioid-induced gastrointestinal (GI) side effects: the PACQOL questionnaire. Eur J Pain 2006; 10Suppl. 1: S181–2

    Google Scholar 

  40. Whitehead WE, Drinkwater D, Cheskin LJ, et al. Constipation in the elderly living at home: definition, prevalence, and relationship to lifestyle and health status. J Am Geriatr Soc 1989 May; 37(5): 423–9

    PubMed  CAS  Google Scholar 

  41. Panchal SJ, Muller-Schwefe P, Wurzelmann JI. Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden. Int J Clin Pract 2007 Jul; 61(7): 1181–7

    Article  PubMed  CAS  Google Scholar 

  42. Sonnenberg A, Koch TR. Epidemiology of constipation in the United States. Dis Colon Rectum 1989 Jan; 32(1): 1–8

    Article  PubMed  CAS  Google Scholar 

  43. Vella-Brincat J, Macleod AD. Adverse effects of opioids on the central nervous systems of palliative care patients. J Pain Palliat Care Pharmacother 2007; 21(1): 15–25

    Article  PubMed  Google Scholar 

  44. Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with the use of morphine and opiates. J Intern Med 2006 Jul; 260(1): 76–87

    Article  PubMed  CAS  Google Scholar 

  45. Kotowa W, Voelkl M, Hass B, et al. Estimated costs associated with different fracture risks related to opioid treatment in Germany: PPN3 [abstract]. Value Health 2007; 10(3): A172

    Article  Google Scholar 

  46. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993 Mar 3; 85(5): 365–76

    Article  PubMed  CAS  Google Scholar 

  47. Gaertner J, Radbruch L, Giesecke T, et al. Assessing cognition and psychomotor function under long-term treatment with controlled release oxycodone in non-cancer pain patients. Acta Anaesthesiol Scand 2006 Jul; 50(6): 664–72

    Article  PubMed  CAS  Google Scholar 

  48. Portenoy RK. Opioid therapy for chronic nonmalignant pain: a review of the critical issues. J Pain Symptom Manage 1996 Apr; 11(4): 203–17

    Article  PubMed  CAS  Google Scholar 

  49. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician 2008 Mar; 11(2 Suppl.): S105–20

    PubMed  Google Scholar 

  50. Mercadante S. Opioid titration in cancer pain: a critical review. Eur J Pain 2007 Nov; 11(8): 823–30

    Article  PubMed  CAS  Google Scholar 

  51. Vielvoye-Kerkmeer AP, Mattern C, Uitendaal MP. Transdermal fentanyl in opioid-naive cancer pain patients: an open trial using transdermal fentanyl for the treatment of chronic cancer pain in opioid-naive patients and a group using codeine. J Pain Symptom Manage 2000 Mar; 19(3): 185–92

    Article  PubMed  CAS  Google Scholar 

  52. van Seventer R, Smit JM, Schipper RM, et al. Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment of patients not using opioids for mild-to-moderate pain. Curr Med Res Opin 2003; 19(6): 457–69

    Article  PubMed  Google Scholar 

  53. Moore RA, Derry S, Phillips CJ, et al. Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice. BMC Musculoskelet Disord 2006; 7: 79

    Article  PubMed  Google Scholar 

  54. Moore RA, Phillips CJ. Cost of NSAID adverse effects to the UK National Health Service. J Drug Assessment 1999; 2: 207–17

    Google Scholar 

  55. Segasothy M, Samad SA, Zulfigar A, et al. Chronic renal disease and papillary necrosis associated with the long-term use of nonsteroidal anti-inflammatory drugs as the sole or predominant analgesic. Am J Kidney Dis 1994 Jul; 24(1): 17–24

    PubMed  CAS  Google Scholar 

  56. Heerdink ER, Leufkens HG, Herings RM, et al. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med 1998 May 25; 158(10): 1108–12

    Article  PubMed  CAS  Google Scholar 

  57. McGoldrick MD, Bailie GR. Nonnarcotic analgesics: prevalence and estimated economic impact of toxicities. Ann Pharmacother 1997 Feb; 31(2): 221–7

    PubMed  CAS  Google Scholar 

  58. Chevat C, Pena BM, Al MJ, et al. Healthcare resource utilisation and costs of treating NSAID-associated gastro-intestinal toxicity: a multinational perspective. Pharmaco-economics 2001; 19Suppl. 1: 17–32

    Article  Google Scholar 

  59. Ashby MA, Martin P, Jackson KA. Opioid substitution to reduce adverse effects in cancer pain management. Med J Aust 1999 Jan 18; 170(2): 68–71

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Editorial support for this review was provided by inScience Communications, a Wolters Kluwer business, and was funded by Grünenthal GmbH. The author has previously acted as a consultant to Grünenthal GmbH.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lieven Annemans.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Annemans, L. Pharmacoeconomic Impact of Adverse Events of Long-Term Opioid Treatment for the Management of Persistent Pain. Clin. Drug Investig. 31, 73–86 (2011). https://doi.org/10.1007/BF03256935

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256935

Keywords

Navigation