Framing of the opioid problem in cancer pain management in Canada

Perspectives in Oncology


Framing of the opioid problem in cancer pain management in Canada


R. Asthana, MSc*, S. Goodall, BSc*, J. Lau, MD, C. Zimmermann, MD PhD, P.L. Diaz, PhD*, A.B. Wan, MSc*, E. Chow, MBBS PhD*, C. De Angelis, PharmD*



doi: http://dx.doi.org/10.3747/co.26.4517


ABSTRACT

Two guidelines about opioid use in chronic pain management were published in 2017: the Canadian Guideline for Opioids for Chronic Non-Cancer Pain and the European Pain Federation position paper on appropriate opioid use in chronic pain management. Though the target populations for the guidelines are the same, their recommendations differ depending on their purpose. The intent of the Canadian guideline is to reduce the incidence of serious adverse effects. Its goal was therefore to set limits on the use of opioids. In contrast, the European Pain Federation position paper is meant to promote safe and appropriate opioid use for chronic pain.

The content of the two guidelines could have unintentional consequences on other populations that receive opioid therapy for symptom management, such as patients with cancer. In this article, we present expert opinion about those chronic pain management guidelines and their impact on patients with cancer diagnoses, especially those with histories of substance use disorder and psychiatric conditions. Though some principles of chronic pain management can be extrapolated, we recommend that guidelines for cancer pain management should be developed using empirical data primarily from patients with cancer who are receiving opioid therapy.

KEYWORDS: Chronic pain, cancer pain, pain, opioids, Canadian pain guideline (2017), European pain guideline (2017), mental health, substance use disorders

INTRODUCTION

The World Health Organization has described opioids as essential medicines for pain control. However, there are multiple barriers to opioid use that prevent health care providers from using opioids to their full potential for adequate pain control1. Opioid distribution shows substantial inequity, with 17% of the world’s population consuming 92% of the world’s supply2. In 2009, the proportions of the total global morphine supply consumed by the United States, Europe, and Canada were 56%, 28%, and 6% respectively3. Even in countries with access to prescription opioids, pain is inadequately treated, with one third of patients with cancer experiencing chronic pain3,4. Barriers to opioid use by primary care physicians (pcps) include insufficient knowledge, fear of dependence, diversion, and regulatory scrutiny2. Efforts are therefore focused on limiting opioid use5.

Since the start of the 2000s, opioid prescriptions have increased, with a parallel increase in addiction and the prevalence of aberrant opioid-taking behaviours6,7. In 2016, North American authorities declared public health crises because of the epidemic-like overdose deaths from prescription, diverted, and illicit opioids8,9. In response, the Michael G. DeGroote National Pain Centre at McMaster University collaborated with Health Canada to develop the 2017 Canadian Guideline for Opioids for Chronic Non- Cancer Pain5, herein called the 2017 cg. Although it has been explicitly stated that the guideline does not address opioid use for acute pain5, patients with cancer or in palliative care or those with substance-use disorders (sud) could inadvertently be affected by the recommendations.

Opioids are important for cancer pain treatment and the 2017 cg might influence how opioids are prescribed to cancer patients10. Cancer pain is prevalent in 39% of patients after treatment, in 55% during treatment, and in 66% with metastatic disease11. Almost 38% of patients with metastatic disease report moderate to severe pain, and almost 33% are undertreated for their pain11,12. Another review stated that 51% of all cancer patients experience pain regardless of cancer type and stage, but that up to 66% of patients with metastatic disease experience pain13. Canadian research indicates that opioid prescription declined by 12% in Ontario between 2010 and 2013, and by 2% across Canada between 2013 and 20156,7. However, opioid-related hospital visits increased by 13%, and the rate of drug abuse remained the same6,7.

Opioid use and its associated harms are significantly less frequent in Europe than in North America14. In 2017, the European Pain Federation (epf) released a position paper to promote opioid use for chronic pain management15. The epf convened to address poorly managed pain, rather than opioid-related harms15. The epf provides expert consensus recommendations for pcps and other non-specialist health care professionals about safe opioid use15.

The purpose of this article is to compare the Canadian guideline with the epf guideline for opioid use in chronic pain to demonstrate how different research questions concerning a similar topic can lead to different outcomes. Each guideline elected to focus on a different aspect of opioids: The epf guideline focuses on the public health concern of poorly managed chronic pain; the Canadian guideline is primarily concerned with reducing opioid-related harms.

Guideline Development and Format

The epf developed its guideline by summarizing the evidence. If data were lacking, European physicians and scientists provided recommendations15. Details about the development of the paper were not published, nor were patients involved15. A flow chart is used as a stepwise guide to opioid initiation and treatment of opioid-related adverse effects15.

To develop the 2017 cg, Busse et al.16 examined available evidence using the grade (Grading of Recommendations, Assessment, Development and Evaluation) system. The guideline panel consisted of 13 clinicians and 2 patient representatives. Clinicians with diverse opinions about opioid use for chronic pain participated in advisory roles in the associated clinical expert committee, and 16 patients with chronic pain formed the patient advisory committee5,16. The 2017 cg is a revision of the 2010 Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain17. The 2010 guideline was difficult to implement because of suboptimal formatting and excessive length18. The 2017 cg therefore uses concise statements to guide clinical assessments. The sections focus on detailed recommendations, practical information, strength of evidence, preferences and values, resources, and other considerations. The authors partnered with Making GRADE the Irresistible Choice to provide the guideline online.

Opioid Therapy Initiation

Both guidelines affirm that non-opioid therapy should be implemented and exhausted before opioids are started15. Based on the quality of the evidence and proven efficacy, the 2017 cg specifies the eligible patient populations and whether individuals in those populations should be considered for opioids5. It recommends controlled-release opioids for continuous pain and fast-acting formulas for activity-related pain5. The epf guideline requires a comprehensive evaluation of the patient to determine whether opioid therapy is suitable15. Patients discuss and document treatment goals with their pcp, and they receive education about the benefits and risks of opioids and about appropriate use and storage. The epf recommends controlled-release opioids to enhance compliance, reduce breakthrough pain, and decrease the likelihood of addiction15.

Opioid Switching and Maintenance

Both guidelines state that patients receiving opioid therapy should be monitored to ensure that treatment remains beneficial and necessary19. Both guidelines recommend starting at the lowest dose, with a supervised trial period19. The 2017 cg suggests to start at a dose less than a 50 mg morphine-equivalent daily dose (medd) and to maintain the dose at less than 90 mg medd. Involving pain specialists if a patient requires a higher opioid dose is encouraged19. The epf recommends seeking expert opinion at doses more than 120 mg medd19.

However, consensus about equianalgesic medd opioid conversion ratios is lacking. Recommendations with specific dose cut-offs might not be appropriate given the individual response to opioids19. Although the risk of overdose or sud increases as the daily dose rises, there is no clear threshold dose; respiratory distress can occur at less than 20 mg medd20,21. For patients switching between opioids, both guidelines suggest calculating the medd of the new drug and reducing the dose by 25%–50%5,15. Alternatively, pcps can lower the original opioid dose while gradually increasing the new opioid dose5,15. The daily dose of one opioid does not necessarily exert the same effects as the daily dose of another opioid19. Both guidelines recommend considering patient-specific attributes such as organ function, drug tolerance, age, and body surface area when prescribing opioids19.

Both guidelines recommend tapering and discontinuing opioids for patients not meeting treatment goals or those demonstrating signs of misuse5,15. The timing for tapering opioid therapy differs between the guidelines. The 2017 cg recommends tapering for anyone receiving more than 90 mg medd5. The epf guideline recommends tapering after 6 months, followed by a “drug holiday” to determine whether opioid therapy is required15. The focus on dose alone could propagate a fear of regulatory sanctions and encourage negative attitudes toward patients who require higher doses.

Cancer Pain Management

Cancer survivors can continue to experience physiologically complex pain years after cessation of chemotherapy22,23. The prevalence of chronic pain in survivors ranges from 16% to 50%; care for those patients is often transferred back to pcps24,25. The pcps might be more reluctant than specialists to prescribe opioids, likely because of a lack of training, potentially making cancer survivors vulnerable to the effect of the new guideline24. Almost one third of pcps report delaying opioid prescriptions for patients with cancer until the terminal phase of disease or unbearable pain24. A pan-European survey about chronic pain management revealed that 84% of pcps perceived their training in pain management to be inadequate26. Others, citing lack of supportive resources, reported allocating insufficient time to assess and monitor patients2729. The World Health Organization guideline for cancer pain management proposes opioids for severe pain21, and yet systematic reviews of the quality of cancer pain management in Europe, North America, Asia, Africa, and Australia found that one third of patients do not receive pain medication proportional to their pain intensity4,10,24,30. In addition, 37% of pcps cited fear of regulatory review as a reason to avoid prescribing opioids, and some admitted to reducing opioid doses to avoid investigation31. Furthermore, patients taking chronic opioids have reported stigmatization32,33. An estimated 34%–86% of health care professionals overestimated addiction or tolerance likelihood24,34. In another study, 28% of pcps believed that any patient given opioids is at an increased risk for addiction35.

The inevitability of pain for cancer pat ients is known36. Patients with painful bone metastases are often under-medicated36. Opioids can be used at all stages of bone metastases36. Considering that cost and access to opioids are not a limitation for Canadian palliative care physicians and oncologists, pain management guidelines play a significant role in the under-prescription of opioids to patients with metastatic disease36. Increasing physician and patient education about opioid use can improve pain management in cancer patients36.

Some patients might require opioids alone or in combination with other substances for continuous drug delivery to achieve appropriate analgesia13. Multidisciplinary symptom management is therefore required to achieve adequate pain control for patients with metastatic disease13. Implementing pain management strategies from the early stages of cancer to metastatic disease—before the pain is unbearable—would be beneficial13. Canadian recommendations for breakthrough cancer pain state that 5%–20% of the total daily opioid dose can be used to treat breakthrough cancer pain and that using a “two-formulations” approach to target different mechanisms of action can improve pain control37. Patients receiving opioids should be closely monitored, but addiction concerns should not prevent physicians from prescribing opioids37. The 2017 cg could hinder receipt of appropriate pain management for those patients and thus further compromise their quality of life.

Mental health disorders, including depression and anxiety, are prevalent in 50% of patients with chronic pain and in 29%–38% of patients with cancer38. The association between psychiatric conditions and pain is well-established; the treatment of such conditions could improve pain control, and the psychiatric illness might improve because of adequate pain management39. The epf guideline does not comment on the issue of concurrent mental health and opioid prescription. The 2017 cg advises postponing opioid therapy until psychiatric disorders are stable5. Exclusion of patients with such disorders from opioid therapy for chronic pain management could negatively affect their quality of life and damage the physician–patient relationship39.

Neither guideline addresses obstacles to opioid prescription and pain management in susceptible populations. Patients with sud often require higher doses of opioids, and yet they are prescribed lower doses than patients without sud40. Attitudes, beliefs, knowledge, and fear of regulatory sanctions on the part of pcps can prevent access to opioids in people with sud and psychiatric conditions41. The epf guideline states that opioids should be considered in patients with chronic pain regardless of underlying comorbidities, and referral to a specialist is recommended for those at increased risk for sud15. The 2017 cg suggests that patients with sud be jointly treated by pain and addictions specialists5. However, there is a strong recommendation to exclude those patients from opioid therapy, even if non-opioid therapy has been used and proved to be ineffective5.

SUMMARY

Addressing the underlying sources of pain is important for effective pain management. Patients with cancer can experience the serious harms associated with opioid addiction and misuse just as patients with chronic non-cancer pain can. We do not intend to suggest that opioids are appropriate for all cancer patients; rather, we recommend an evidence-based, open-minded strategy for opioid use in pain management. Neither the Canadian nor the epf guideline is ideal for cancer pain. The dose cut-offs in the 2017 cg could lead pcps to follow them as “rules” rather than recommendations and could result in fear of opioids and increased regulatory scrutiny, hindering access to pain control in vulnerable populations. The Canadian guideline might result in negative outcomes, such as undertreatment, stigmatization of patients, and damage to the physician–patient relationship, especially for cancer patients with psychiatric disorders and sud. The epf guideline is less restrictive, but could be confusing for providers inexperienced in cancer pain management. Safe and appropriate opioid use should be promoted for all patients and not just for those with addiction. Given all the foregoing considerations, we recommended that an update to the guidelines for cancer pain management be undertaken.

ACKNOWLEDGMENTS

We acknowledge the generous support of the Rudolph P. Bratty Family Foundation, the Michael and Karyn Goldstein Cancer Research Fund, the Joey and Mary Furfari Cancer Research Fund, the Pulenzas Cancer Research Fund, the Joseph and Silvana Melara Cancer Research Fund, and the Ofelia Cancer Research Fund.

CONFLICT OF INTEREST DISCLOSURES

We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

AUTHOR AFFILIATIONS

*Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON,
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON,
Princess Margaret Cancer Centre, University of Toronto, Toronto, ON.

REFERENCES

1 World Health Organization (who), Expert Committee on the Selection and Use of Essential Medicines. Executive Summary: The Selection and Use of Essential Medicines. Geneva, Switzerland: who; 2017. [Available online at: http://www.who.int/medicines/publications/essentialmedicines/EML_2017_ExecutiveSummary.pdf?ua=1; cited 10 September 2018]

2 Berterame S, Erthal J, Thomas J, et al. Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet 2016;387:1644–56.
cross-ref  pubmed  

3 International Narcotics Control Board (incb). Report of the International Narcotics Control Board on the Availability of Internationally Controlled Drugs: Ensuring Adequate Access for Medical and Scientific Purposes. Vienna, Austria: incb; 2010. [Available online at: https://www.unodc.org/documents/lpo-brazil/noticias/2011/03-marco/Jife/Report_of_the_Board_on_the_availability_of_controlled_substances.pdf; cited 10 September 2018]

4 Greco M, Roberto A, Corli O, et al. Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer. J Clin Oncol 2014;32:4149–54.
cross-ref  pubmed  

5 Busse JW, Craigie S, Juurlink DN, et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ 2017;189:E659–66.
cross-ref  pubmed  pmc  

6 Fernandes K, Martins D, Juurlink D, et al. High-dose opioid prescribing and opioid-related hospitalization: a population- based study. PLoS One 2016;11:e0167479. [Erratum in: PLoS One 2017;12:e0170834]
cross-ref  

7 Statistics Canada. Canadian Tobacco, Alcohol and Drugs (CTADS): 2015 Summary. Ottawa, ON: Government of Canada; 2017.

8 Felter C. The U.S. Opioid Epidemic [Web article]. Congers, NY: Council on Foreign Relations; 2017. [Available at: https://www.cfr.org/backgrounder/us-opioid-epidemic; cited 10 September 2018]

9 Health Canada. Federal Action on Opioids [Web page]. Ottawa, ON: Government of Canada; 2016. [Available at: https://www.canada.ca/en/health-canada/services/substance-abuse/prescription-drug-abuse/opioids/federal-actions.html; cited 10 September 2018]

10 World Health Organization (who). WHO’s cancer pain ladder for adults [Web page]. Geneva, Switzerland: who; n.d. [Available at: http://www.who.int/cancer/palliative/painladder/en; cited 10 September 2018]

11 van den Beuken–van Everdingen MH, Hochstenbach LM, Joosten EA, Tjan-Heijnen VC, Janssen DJ. Update on prevalence of pain in patients with cancer : systematic review and meta-analysis. J Pain Symptom Manage 2016;51:1070–90.
cross-ref  

12 Vuong S, Pulenzas N, DeAngelis C, et al. Inadequate pain management in cancer patients attending an outpatient palliative radiotherapy clinic. Support Care Cancer 2016;24:887–92.
cross-ref  

13 Hochberg U, Elgueta MF, Perez J. Interventional analgesic management of lung cancer pain. Front Oncol 2017;7:17.
cross-ref  pubmed  pmc  

14 Van Amsterdam J, Van den Brink W. The misuse of prescription opioids: a threat for Europe? Curr Drug Abus Rev 2015;8:3–14.
cross-ref  

15 O’Brien T, Christrup LL, Drewes AM, et al. European Pain Federation position paper on appropriate opioid use in chronic pain management. Eur J Pain 2017;21:3–19.
cross-ref  

16 Busse JW, Craigie S, Juurlink DN, et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ 2017;189:E659–66.
cross-ref  pubmed  pmc  

17 Kahan M, Mailis-Gagnon A, Wilson L, Srivastava A on behalf of the National Opioid Use Guideline Group. Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 1: general population. Can Fam Physician 2011;57:1257–66,e407–18.
pubmed  pmc  

18 Chang Y, Zhu K, Florez I, et al. Attitudes toward the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain: a qualitative study. J Opioid Manag 2016;12:377–87.
cross-ref  

19 Fudin J, Pratt Cleary J, Schatman ME. The medd myth: the impact of pseudoscience on pain research and prescribing-guideline development. J Pain Res 2016;9:153–6.
pmc  

20 Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort study of the impact of high-dose opioid analgesics on overdose mortality. Pain Med 2016;17:85–98.

21 Zedler B, Xie L, Wang L, et al. Development of a risk index for serious prescription opioid–induced respiratory depression or overdose in Veterans’ Health Administration patients. Pain Med 2015;16:1566–79.
cross-ref  pubmed  pmc  

22 Chiu N, Zhang L, Dent R, et al. A prospective study of docetaxel-associated pain syndrome. Support Care Cancer 2018;26:203–11.
cross-ref  

23 Loprinzi CL, Reeves BN, Dakhil SR, et al. Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study ncctg N08C1. J Clin Oncol 2011;29:1472–8.
cross-ref  pubmed  pmc  

24 Kwon JH. Overcoming barriers in cancer pain management. J Clin Oncol 2014;32:1727–33. [Erratum in: J Clin Oncol 2014;32:2117]
cross-ref  pubmed  

25 Kurita GP, Sjøgren P. Pain management in cancer survivorship. Acta Oncol (Madr) 2015;54:629–34.
cross-ref  

26 Johnson M, Collett B, Castro-Lopes JM. The challenges of pain management in primary care: a pan-European survey. J Pain Res 2013;6:393–401.
pubmed  pmc  

27 Harle CA, Bauer SE, Hoang HQ, Cook RL, Hurley RW, Fillingim RB. Decision support for chronic pain care: how do primary care physicians decide when to prescribe opioids? A qualitative study. BMC Fam Pract 2015;16:48.
cross-ref  pubmed  pmc  

28 Krebs EE, Bergman AA, Coffing JM, Campbell SR, Frankel RM, Matthias MS. Barriers to guideline-concordant opioid management in primary care—a qualitative study. J Pain 2014;15:1148–55.
cross-ref  pubmed  

29 Zuccaro SM, Vellucci R, Sarzi-Puttini P, Cherubino P, Labianca R, Fornasari D. Barriers to pain management : focus on opioid therapy. Clin Drug Investig 2012;32(suppl 1):11–19.
cross-ref  

30 Deandrea S, Montanari M, Moja L, Apolone G. Prevalence of undertreatment in cancer pain. A review of published literature. Ann Oncol 2008;19:1985–91.
cross-ref  pubmed  pmc  

31 Wolfert MZ, Gilson AM, Dahl JL, Cleary JF. Wisconsin physicians’ knowledge, beliefs, attitudes, and prescribing practices. Pain Med 2010;11:425–34.
cross-ref  

32 Brooks EA, Unruh A, Lynch M. Exploring the lived experience of adults using prescription opioids to manage chronic noncancer pain. Pain Res Manag 2015;20:15–22.
cross-ref  pubmed  pmc  

33 Peppin JF. The marginalization of chronic pain patients on chronic opioid therapy. Pain Physician 2009;12:493–8.
pubmed  

34 Oldenmenger WH, Sillevis Smitt PA, van Dooren S, Stoter G, van der Rijt CC. A systematic review on barriers hindering adequate cancer pain management and interventions to reduce them: a critical appraisal. Eur J Cancer 2009;45:1370–80.
cross-ref  pubmed  

35 Weinstein SM, Laux LF, Thornby JI, et al. Physicians’ attitudes toward pain and the use of opioid analgesics: results of a survey from the Texas Cancer Pain Initiative. South Med J 2000;93:479–87.
cross-ref  pubmed  

36 Kirou-Mauro AM, Hird A, Wong J, et al. Has pain management in cancer patients with bone metastases improved? A seven-year review at an outpatient palliative radiotherapy clinic. J Pain Symptom Manage 2009;37:77–84.
cross-ref  

37 Daeninck P, Gagnon B, Gallagher R, et al. Canadian recommendations for the management of breakthrough cancer pain. Curr Oncol 2016;23:96–108.
cross-ref  pubmed  pmc  

38 Mitchell AJ, Chan M, Bhatti H, et al. Prevalence of depression, anxiety, and adjustment disorder in oncological, hematological, and palliative-care settings: a meta-analysis of 94 interview-based studies. Lancet Oncol 2011;12:160–74.
cross-ref  pubmed  

39 Hooten WM. Chronic pain and mental health disorders: shared neural mechanisms, epidemiology and treatment. Mayo Clin Proc 2016;91:955–70.
cross-ref  pubmed  

40 Wachholtz A, Ziedonis D, Gonzalez G. Comorbid pain and opioid addiction: psychosocial and pharmacological treatments. Subst Use Misuse 2011;46:1536–52.
cross-ref  pubmed  

41 Dalal S, Bruera E. Access to opioid analgesics and pain relief for patients with cancer. Nat Rev Clin Oncol 2013;10:108–16.
cross-ref  pubmed  


Correspondence to: Rashi Asthana, c/o Carlo De Angelis. Sunnybrook Health Sciences Centre, Odette Cancer Centre, 2075 Bayview Avenue, Room T2-234, Toronto, Ontario M4N 3M5. E-mail: rashi.asthana@mail.utoronto.ca

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Current Oncology, VOLUME 26, NUMBER 3, JUNE 2019








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ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)