Current Anesthesiology Reports

, Volume 8, Issue 4, pp 342–347 | Cite as

Considerations in 2017–2018 for the Use of Opioids in Non-terminal Pain

  • Kenneth S. TsengEmail author
Pain Medicine (GJ Meredith, Section Editor)
Part of the following topical collections:
  1. Pain Medicine


Purpose of Review

Despite external pressure on medical providers to reduce opioid prescribing, patients with chronic, non-terminal pain continue to present to their physicians requesting pharmacologic assistance with low back pain, arthritis, neuropathy, migraine headaches, and other forms of non-terminal pain lasting more than 3 months.

Recent Findings

In the last 2 years, updated systematic meta-analyses and one randomized, controlled trial have still been unable to find evidence of benefit from use of opioid therapy longer than 3 months for treatment of non-terminal pain.


With substantial evidence about the potential risks of opioid use and a relative paucity of evidence supporting their long-term use, prescribers are asked to be more judicious in their selection of patients, continuously weighing the risks and benefits.


Opioid Chronic pain Chronic non-cancer pain Chronic non-terminal pain 


Compliance with Ethical Standards

Conflict of Interest

Kenneth S. Tseng declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Associated Press. Number of prescriptions for opioid painkillers drops dramatically in U.S. [Internet]. NBC News. 2018 April 20. [cited 2018 October 8]. Available from:
  2. 2.
    • Qaseem A, Wilt TJ, McLean RM, Forciea MA. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166(7):514–30 Consensus guideline from ACP for treatment of low back pain by primary care physicians.CrossRefGoogle Scholar
  3. 3.
    American Society of Anesthesiologists Joint Committee on Pain Medicine and Ad Hoc Committee on Prescription Opioid Abuse. Considerations for long-term opioid use in chronic, non-cancer pain conditions. [cited; Available from:
  4. 4.
    •• Busse JW, Craigie S, Juurlink DN, Buckley DN, Wang L, Couban RJ, et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ. 2017;189(18):E659–E66 Consensus Canadian guidelines, supported by grants from Canadian Institutes of Health Research and Health Canada. CrossRefGoogle Scholar
  5. 5.
    •• Faculty of Pain Medicine. Opiods Aware: a resource for patients and healthcare professionals to support prescribing of opioid medicines for pain. 2015 [cited; Available from: Web-based guidelines from Faculty of Pain Medicine, Royal College of Anaesthetists, with support from the British Pain Society and Public Health England.
  6. 6.
    •• Faculty of Pain Medicine, Austalian and New Zealand College of Anaesthetists (FPMANZCA). Recommendations regarding the use of opioid analgesics in patients with chronic non-cancer pain. 2015 [cited; Available from: Consensus Australian guidelines.
  7. 7.
    •• Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain - United States, 2016. MMWR Recomm Rep. 65(1):1–49 Systematic review of studies performed up until April 2015. They found insufficient evidence to answer the question of the efficacy of long-term opioid therapy versus non-opioid alternatives. Google Scholar
  8. 8.
    Virginia Board of Medicine. Regulations governing prescribing of opioids and buprenorphine [Internet]. Henrico, Virginia: Commonwealth of Virginia, 2018. Regulation number 18 VAC 85-21-10. [cited 2018 October 8]. Available from:
  9. 9.
    Brennan T. The balancing act: helping ensure appropriate access to opioids while minimizing risk. 2017 February 28 [cited; Available from:
  10. 10.
    Tseng KS, Chen LL. Opioid therapy for long-term pain control in non-terminal patients. Curr Anesthesiol Rep. 2016;6(4):305–13.CrossRefGoogle Scholar
  11. 11.
    Derry S, Stannard C, Cole P, Wiffen PJ, Knaggs R, Aldington D, et al. Fentanyl for neuropathic pain in adults. Cochrane Database Syst Rev. 2016;10:CD011605.PubMedGoogle Scholar
  12. 12.
    Gaskell H, Derry S, Stannard C, Moore RA. Oxycodone for neuropathic pain in adults. Cochrane Database Syst Rev. 2016;7:CD010692.PubMedGoogle Scholar
  13. 13.
    Cooper TE, Chen J, Wiffen PJ, Derry S, Carr DB, Aldington D, et al. Morphine for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;5:CD011669.PubMedGoogle Scholar
  14. 14.
    Stannard C, Gaskell H, Derry S, Aldington D, Cole P, Cooper TE, et al. Hydromorphone for neuropathic pain in adults. Cochrane Database Syst Rev. 2016;24(5):CD011604.Google Scholar
  15. 15.
    • Mcnicol ED, Ferguson MC, Schumann R. Methadone for neuropathic pain in adults. Cochrane Database Syst Rev. 2017;5:CD012499 Cochrane library systematic review of three small RCTs. Two studies were combined to show 11/29 subjects reported 30% improvement in symptoms versus 7/29 subjects on placebo. One study reported statistically significant improvement in pain intensity with methadone 20 mg/day but not 10 mg/day. These studies provided very low-quality evidence due to risk of bias, short study duration, crossover study design, and heterogeneity of findings. PubMedGoogle Scholar
  16. 16.
    Duehmke RM, Derry S, Wiffen PJ, Bell RF, Aldington D, Moore RA. Tramadol for neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6:CD003726.PubMedGoogle Scholar
  17. 17.
    • Gaskell H, Moore RA, Derry S, Stannard C. Oxycodone for pain in fibromyalgia in adults. Cochrane Database Syst Rev. 2016;9:CD012329 Cochrane library systematic review of oxycodone for treatment of fibromyalgia, which was previously included in systematic reviews of neuropathic pain. PubMedGoogle Scholar
  18. 18.
    Goldenberg DL, Clauw DJ, Palmer RE, Clair AG. Opioid use in fibromyalgia: a cautionary tale. Mayo Clin Proc. 2016 May;91(5):640–8.CrossRefGoogle Scholar
  19. 19.
    • Santos J, Alarcao J, Fareleira F, Vaz-Carneiro A, Costa J. Tapentadol for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2015;27(5):CD009923 Cochrane library systematic review of four RCTs comparing tapentadol ER, oxycodone CR, and placebo for chronic musculoskeletal pain. Three with 12-week follow-up, one open-label study lasting 52 weeks. All four studies were funded by the drug manufacturer. Compared with placebo, tapentadol ER was associated with a mean reduction of 0.56 on 11-point NRS. Three out of 10 patients on tapentadol reported greater than 50% improvement, compared with 2 out of 10 on oxycodone or placebo. Study limitations were significant: including high heterogeneity in some outcomes, high rates of withdrawal from the studies, and lack of data for some primary outcomes. Google Scholar
  20. 20.
    Stone MT, Weed V, Kulich RJ. Opioid treatment of migraine: risk factors and behavioral issues. Curr Pain Headache Rep. 2016 Sep;20(9):51.CrossRefGoogle Scholar
  21. 21.
    Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005 Jan;113(1–2):9–19.CrossRefGoogle Scholar
  22. 22.
    Furlan AD, Reardon R, Weppler C. Opioids for chronic noncancer pain: a new Canadian practice guideline. CMAJ. 2010 Jun 15;182(9):923–30.CrossRefGoogle Scholar
  23. 23.
    • Gomes T, Juurlink DN, Antoniou T, Mamdani MM, Paterson JM, van den Brink W, et al. PLoS Med. 2017;14(10):e1002396 New evidence suggesting an increased risk of unintentional opioid overdose when co-prescribing with gabapentin.CrossRefGoogle Scholar
  24. 24.
    Geissert P, Hallvik S, Van Otterloo J, O'Kane N, Alley L, Carson J, et al. High-risk prescribing and opioid overdose: prospects for prescription drug monitoring program-based proactive alerts. Pain. 2018 Jan;159(1):150–6.CrossRefGoogle Scholar
  25. 25.
    Gomes T, Greaves S, van den Brink W, Antoniou T, Mamdani MM, Paterson JM, et al. Pregabalin and the risk for opioid-related death: a nested case-control study. Ann Intern Med. 2018 Aug 21.Google Scholar
  26. 26.
    Chou R, Deyo R, Devine B, Hansen R, Sullivan S, Jarvik JG, et al. The effectiveness and risks of long-term opioid treatment of chronic pain. Evidence Report/Technology Assessment No. 218. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2012-00014-I.) AHRQ Publication No. 14-E005-EF. Rockville, MD: Agency for Healthcare Research and Quality, 2014.Google Scholar
  27. 27.
    •• Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: The SPACE randomized clinical trial. JAMA. 2018;319(9):872–82 RCT of US Veterans Administration primary care clinic patients with chronic back pain or hip or knee osteoarthritis. Patients were randomized to either opioid (morphine sulfate, oxycodone, or hydrocodone/acetaminophen) or non-opioid (acetaminophen or NSAID) and followed for 12 months. Primary outcome was pain-related function (Brief Pain Inventory [BPI] interference score) and the secondary outcome was pain intensity (BPI severity). There was no significant difference between the groups in pain-related function, and patients in the non-opioid group reported significantly better pain severity score at 12 months. CrossRefGoogle Scholar
  28. 28.
    Bigal ME. Opioids vs nonopioids for chronic Back, hip, or knee pain. JAMA. 2018;320(5):507.CrossRefGoogle Scholar
  29. 29.
    • American Pain Society. Guideline for the use of chronic opioid therapy in chronic noncancer pain: evidence review. Chicago: American Pain Society, American Academy of Pain Medicine Opioids Guidelines Panel; 2009. The APS published the first systematic review of opioid therapy for chronic non-terminal pain that laid the ground work for the CDC recommendations. Google Scholar
  30. 30.
    Hayhurst CJ, Durieux ME. Differential opioid tolerance and opioid-induced hyperalgesia: a clinical reality. Anesthesiology. 2016 Feb;124(2):483–8.CrossRefGoogle Scholar
  31. 31.
    Els C, Jackson TD, Hagtvedt R, Kunyk D, Sonnenberg B, Lappi VG, et al. High-dose opioids for chronic non-cancer pain: an overview of Cochrane reviews. Cochrane Database Syst Rev. 2017;10:CD012299.PubMedGoogle Scholar
  32. 32.
    Quang-Cantagrel ND, Wallace MS, Magnuson SK. Opioid substitution to improve the effectiveness of chronic noncancer pain control: a chart review. Anesth Analg. 2000;90(4):933–7.CrossRefGoogle Scholar
  33. 33.
    Smith HS. Opioid metabolism. Mayo Clin Proc. 2009;84(7):613–24.CrossRefGoogle Scholar
  34. 34.
    Vissers KC, Besse K, Hans G, Devulder J, Morlion B. Opioid rotation in the management of chronic pain: where is the evidence? Pain Pract. 2010;10(2):85–93.CrossRefGoogle Scholar
  35. 35.
    Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE, Caudle KE, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95(4):376–82.CrossRefGoogle Scholar
  36. 36.
    Yoshida K, Nishizawa D, Ide S, Ichinohe T, Fukuda KI, Ikeda K. A pharmacogenetics approach to pain management. Neuropsychopharmacol Rep. 2018;38(1):2–8.CrossRefGoogle Scholar
  37. 37.
    • Els C, Jackson TD, Kunyk D, Lappi VG, Sonnenberg B, Hagtvedt R, et al. Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017;10:CD012509 Cochrane library systematic review of 16 other Cochrane reviews. Compared to placebo, opioid use associated with an absolute event rate of 78% for any side effect (including constipation, dizziness, nausea, and more serious side effects) and 7.5% for any serious side effect. Known side effects such as addiction, mood disorders, respiratory depression, and sleep disturbance were not included in the reviewed articles. PubMedGoogle Scholar
  38. 38.
    Miller M, Barber CW, Leatherman S, Fonda J, Hermos JA, Cho K, et al. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Intern Med. 2015;175(4):608–15.CrossRefGoogle Scholar
  39. 39.
    Fine PG, Mahajan G, McPherson ML. Long-acting opioids and short-acting opioids: appropriate use in chronic pain management. Pain Med. 2009;10(Suppl 2):S79–88.CrossRefGoogle Scholar
  40. 40.
    Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003;349(20):1943–53.CrossRefGoogle Scholar
  41. 41.
    Ghodke A, Barquero S, Chelminski PR, Ives TJ. Short-acting opioids are associated with comparable analgesia to long-acting opioids in patients with chronic osteoarthritis with a reduced opioid equivalence dosing. Pain Med. 2017.Google Scholar
  42. 42.
    Teng Z, Zhu Y, Wu F, Zhang X, Zhang C, Wang S, et al. Opioids contribute to fracture risk: a meta-analysis of 8 cohort studies. PLoS One. 2015;10(6):e0128232.CrossRefGoogle Scholar
  43. 43.
    Rubinstein A, Carpenter DM. Elucidating risk factors for androgen deficiency associated with daily opioid use. Am J Med. 2014;127(12):1195–201.CrossRefGoogle Scholar
  44. 44.
    Hina N, Fletcher D, Poindessous-Jazat F, Martinez V. Hyperalgesia induced by low-dose opioid treatment before orthopaedic surgery: an observational case-control study. Eur J Anaesthesiol. 2015;32(4):255–61.CrossRefGoogle Scholar
  45. 45.
    Gomes T, Redelmeier DA, Juurlink DN, Dhalla IA, Camacho X, Mamdani MM. Opioid dose and risk of road trauma in Canada: a population-based study. JAMA Intern Med. 2013;173(3):196–201.47.CrossRefGoogle Scholar
  46. 46.
    Smith K, Mattick RP, Bruno R, Nielsen S, Cohen M, Campbell G, et al. Factors associated with the development of depression in chronic non-cancer pain patients following the onset of opioid treatment for pain. J Affect Disord. 2015;184:72–80.CrossRefGoogle Scholar
  47. 47.
    Coffin PO, Behar E, Rowe C, Santos GM, Coffa D, Bald M, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Ann Intern Med. 2016;165(4):245–52.CrossRefGoogle Scholar
  48. 48.
    Dunne RB. Prescribing naloxone for opioid overdose intervention. Pain Manag. 2018;8(3):197–208.CrossRefGoogle Scholar
  49. 49.
    Cowan DT, Wilson-Barnett J, Griffiths P, Vaughan DJ, Gondhia A, Allan LG. A randomized, double-blind, placebo-controlled, cross-over pilot study to assess the effects of long-term opioid drug consumption and subsequent abstinence in chronic noncancer pain patients receiving controlled-release morphine. Pain Med. 2005;6(2):113–21.CrossRefGoogle Scholar
  50. 50.
    Larochelle MR, Liebschutz JM, Zhang F, Ross-Degnan D, Wharam JF. Opioid prescribing after nonfatal overdose and association with repeated overdose: a cohort study. Ann Intern Med. 2016;164(1):1–9.CrossRefGoogle Scholar
  51. 51.
    Centers for Disease Control and Prevention. Common elements in guidelines for prescribing opioids for chronic pain. Atlanta: US Department of Health and Human Services, CDC; 2015.Google Scholar
  52. 52.
    Ralphs JA, Williams AC, Richardson PH, Pither CE, Nicholas MK. Opiate reduction in chronic pain patients: a comparison of patient-controlled reduction and staff controlled cocktail methods. Pain. 1994;56(3):279–88.CrossRefGoogle Scholar
  53. 53.
    Tennant FS Jr, Rawson RA. Outpatient treatment of prescription opioid dependence: comparison of two methods. Arch Intern Med. 1982;142(10):1845–7.CrossRefGoogle Scholar
  54. 54.
    • Eccleston C, Fisher E, Thomas KH, Hearn L, Derry S, Stannard C, et al. Interventions for the reduction of prescribed opioid use in chronic non-cancer pain. Cochrane Database Syst Rev. 2017;11:CD010323 An update of the 2013 Cochrane library systematic review evaluating the effectiveness of acupuncture, mindfulness, and CBT at decreasing opioid requirement in patients with chronic non-cancer pain. Overall, results were mixed, with reductions of opioid in both active and control arms. The authors were unable to conclude that any method was superior to the desired outcome. PubMedGoogle Scholar
  55. 55.
    Boseley S. Prescription of opioid drugs continues to rise in England. The Guardian. 2018.Google Scholar
  56. 56.
    Midlov P. Tapering of long-term opioid therapy in chronic pain population. RCT With 12 Months Follow up. Identification No. NCT03485430. 2018. [cited; Available from:

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of AnesthesiologyINOVA Fairfax HospitalFalls ChurchUSA

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