Updates on chronic non-cancer pain management in face of the opioid crisis

Chronic pain not associated with malignancy is experienced by a significant proportion of the Canadian population. As the quality of life and physical functioning are markedly impaired in patients with chronic non-cancer pain, clinicians have commonly turned to opioid therapy for pain management. Since the 1990s, the steady increase in dispensing of prescription opioids has paralleled trends in opioid-related hospitalizations, overdoses, and fatalities. In fact, over-prescription and longterm opioid therapy are among the many root causes fueling Canada’s rise in opioid addiction and opioid-related deaths. Physicians and medical regulators have responded to this public health crisis by developing the 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain. The new evidencebased guideline aims to encourage safe prescribing practices, reduce and eliminate the use of opioid analgesics and promote non-opioid pharmacotherapy. While clear clinical guidelines will optimize physician prescribing patterns, it is imperative to recognize the need for non-pharmacological modalities for pain management, treatment, and care to holistically address the complex roots of opioid abuse. introduction Chronic non-cancer pain (CNCP) is defined as any painful condition that persists for a minimum of three months and is not associated with malignancy.1 A Canadian population-based study using data gathered between 1994 and 2008 reported that 15-19% of adults experienced chronic non-cancer pain at any given time.2 CNCP has bearings on health and financial costs at an individual and population level. Suffering from chronic pain impedes activities of daily living, diminishes physical capacity and quality of life, and enhances disease burden.3 From an economy standpoint, CNCP is one of the foremost causes of healthcare resource consumption and disability among adults in the working-age group.4,5 opioid therapy in non-malignant chronic pain In North America, physicians have commonly depended on opioids for acute, palliative and chronic pain management.1 When all indications for opioid therapy are included, Canada is the second-highest per capita consumer of opiate analgesics in the world, trailing behind the United States.6 High-dose dispensing of morphine, hydromorphone, oxycodone, and fentanyl have increased by 23% between 2006 and 2011 across Canada.7 Albeit there is evidence for the efficacy of opioids in treatment of severe, post-surgical or traumatic acute pain, little evidence supports longUpdates on chronic non-cancer pain management in face of the opioid crisis Gayathri Sivakumar, Alexandra Budure, Elise Quint term opioid therapy in the context of CNCP management.8-9 The sharp increase in prescription opioid analgesic use since the 1990s can be partly explained by aggressive pharmaceutical marketing strategies that encouraged primary care physicians to identify and treat chronic pain with opioids, despite a lack of evidence for using opioids for this indication.10 In 2015, Canadian physicians prescribed opioids 53 times for every 100 people in Canada.11 In Vancouver, BC, a growing trend in the availability of prescription opioids in people who inject drugs is evident between 2010 and 2014.12 Nonmedical prescription opioid use (NMPOU) was significant among street youth and adults, and more than one-third of these individuals engaging in NMPOU had initiated the use of prescription opioids prior to illegal drug use.13 Use of opioid analgesics for CNCP may foster drug tolerance and lead to the prescription of higher-than-recommended doses, increased use of illicit opioids, iatrogenic addiction, accidental poisonings, and fatal overdoses.14 Hospital visits and treatment admission rates for opioid poisoning has increased by over 30% in the period between 2007 and 2015.15 In Ontario, the number of opioid-related deaths per year (excluding heroin-related fatality) has increased from 127 in 1991 to 540 in 2010, and this number continues to rise.7,16 Of the Ontarian patients under social assistance, 1 in 550 patients initiated on long-term opioid therapy faced opioid-related mortality at a median of 2.6 years from the first opioid prescription.17 Nationally, the Public Health Agency of Canada reported 2,458 opioid-related fatalities in 2016.18,19 clinical guidelines for chronic non-cancer pain management The emergence of the opioid epidemic created a strong sense of urgency among clinicians and medical regulators to establish prescribing guidelines for CNCP. In 2010, recommendations proposed by the National Opioid Use Guideline Group for safe and effective opioid utilization was adopted.1 As the opioid crisis became more pronounced, critics argued that many of the prescribing recommendations from the 2010 Canadian Guideline were ambiguous, liberal with opioid use, and most importantly, eminence-based rather than evidence-based.1 Researchers from the McMaster G. DeGroote National Pain Centre have revised the 2010 Canadian Guideline and incorporated evidence-based findings to provide a focused framework for safe opioid prescribing practices for CNCP management.1 The 2017 Canadian Guideline for Opioids for Chronic NonCancer Pain follows standards for trustworthy guidelines and is comprised of three categories of guidance: recommendations, good practice statements, and expert guidance.1 This guideline provides

9] The sharp increase in prescription opioid analgesic use since the 1990s can be partly explained by aggressive pharmaceutical marketing strategies that encouraged primary care physicians to identify and treat chronic pain with opioids, despite a lack of evidence for using opioids for this indication. 10n 2015, Canadian physicians prescribed opioids 53 times for every 100 people in Canada. 11In Vancouver, BC, a growing trend in the availability of prescription opioids in people who inject drugs is evident between 2010 and 2014. 12Nonmedical prescription opioid use (NMPOU) was significant among street youth and adults, and more than one-third of these individuals engaging in NMPOU had initiated the use of prescription opioids prior to illegal drug use. 13Use of opioid analgesics for CNCP may foster drug tolerance and lead to the prescription of higher-than-recommended doses, increased use of illicit opioids, iatrogenic addiction, accidental poisonings, and fatal overdoses. 14Hospital visits and treatment admission rates for opioid poisoning has increased by over 30% in the period between 2007 and 2015. 15In Ontario, the number of opioid-related deaths per year (excluding heroin-related fatality) has increased from 127 in 1991 to 540 in 2010, and this number continues to rise. 7,16Of the Ontarian patients under social assistance, 1 in 550 patients initiated on long-term opioid therapy faced opioid-related mortality at a median of 2.6 years from the first opioid prescription. 17Nationally, the Public Health Agency of Canada reported 2,458 opioid-related fatalities in 2016. 18,19inical guidelines for chronic non-cancer pain management The emergence of the opioid epidemic created a strong sense of urgency among clinicians and medical regulators to establish prescribing guidelines for CNCP.In 2010, recommendations proposed by the National Opioid Use Guideline Group for safe and effective opioid utilization was adopted. 1 As the opioid crisis became more pronounced, critics argued that many of the prescribing recommendations from the 2010 Canadian Guideline were ambiguous, liberal with opioid use, and most importantly, eminence-based rather than evidence-based. 1Researchers from the McMaster G. DeGroote National Pain Centre have revised the 2010 Canadian Guideline and incorporated evidence-based findings to provide a focused framework for safe opioid prescribing practices for CNCP management. 1 The 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain follows standards for trustworthy guidelines and is comprised of three categories of guidance: recommendations, good practice statements, and expert guidance. 1This guideline provides clinicians with ten recommendations which are supported by evidence from randomized controlled trials or observational studies.Additionally, these recommendations are categorized according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system as strong or weak recommendations.Seven of the ten recommendations target harm reduction measures.As well, only four of the ten are strong recommendations.Several suggestions focus on maximizing non-opioid therapy for analgesia and on adding a trial of opioid therapy in patients without substance use and psychiatric disorders who have persistent pain despite optimized non-opioid pharmacotherapy. 1

Table 1. Summary of Canadian Guideline for Opioids for Chronic Non-Cancer Pain
Accompanying the recommendations in this clinical guideline, the good practice statements are supported by indirect evidence, represent common-sense practice, and are associated with assumed large net benefit.These include informed consent, monitoring and adjusting the opioid therapy, and understanding the potential contraindications to opioid prescription.Lastly, the expert guidance provides direction in an area for which there is little or no published evidence.The guidance statements also include strategies for mitigating risks including urine drug screening, treatment agreements, tamper-resistant formulations, fentanyl patch exchange and naloxone kits.

multi-pronged strategies needed in combating the opioid crisis
While these clinical guidelines are necessary to promote best-practice prescribing patterns, they are not sufficient.Other strategies must be implemented simultaneously in order to curb opioid abuse.Evidenced-based clinical guidelines are certainly necessary to optimize prescribing behaviours and mitigate opioid overuse, dependency, and addiction.Trends in opioid dispensing and associated adverse events must be closely monitored to evaluate the impact of public health and policy interventions.Medical colleges across Canada have committed to establishing a national narcotics monitoring network to identify prescribing practices among physicians, high-risk prescribing behaviours and at-risk patients.This information can then be reported back to regulatory bodies. 20The network will also allow physicians to compare their prescribing practices with peers, promote harm reduction measures, and optimize the use of opioids.However, there may be a downside to this increased monitoring.Physicians may be punished for prescribing higher volumes of opioids which could lead to undertreatment of pain.Additionally, the information gathered can help modify postoperative pain management practices, especially in surgical specialties, with long-term opioid therapy. 20ver-prescription of opioid analgesics by physicians is only one of many contributors to the growing opioid crisis.To curb opioid use and abuse, it is imperative to not only treat the physical symptoms of pain but also address upstream factors contributing to pain.Interdisciplinary pain treatment centres (IPTC) recognize pain in a collaborative approach with pain specialists, physical therapists, chiropractors, acupuncturists, massage therapists, mental health providers and addiction specialists.This holistic approach, through a biopsychosocial lens, incorporates nonpharmacological modalities, such as cognitive behaviour therapy (CBT) and mindfulness meditation. 1,14,20A meta-analysis of 65 studies reported an additional 20% reduction in pain with IPTC in comparison to pharmacotherapy. 22Further supporting these findings, a systematic review with 3089 patient participants found a pain reduction of 37% in the CBT group vs 4% in the control. 23n a wide range of studies, IPTC therapy proves to positively impact the perception of pain and pain behavior, in addition to enhancing pain-coping skills, physical function, and psychosocial well-being. 21,24,25Moreover, there is evidence for increased return to clinical procedures

Recommendation
Strength of Recommendation 1.Strong evidence exists to support maximization of non-opioid pharmacotherapy and nonpharmacologic therapy, rather than a trial of opioid therapy.Strong 2. For patients who have continual pain, despite optimization of non-opioid treatment, there is evidence to propose a trial of opioids and monitor for response.Opioid therapy should be terminated if there is no improvement in pain or function.Weak 3.There is strong evidence against the prescription of opioids for patients with an active substance abuse disorder.Strong 4. For patients with an active substance abuse disorder who experience pain even with optimized non-opioid therapy, the psychiatric disorder should be addressed before considering a trial of opioids.Weak 5.For patients with a history of substance abuse disorder who experience pain despite maximization of non-opioid therapy, it is recommended to continue with the current therapy rather than a trial of opioids.Weak 6. Prescribed opioid dosage is recommended to be less than 90 mg morphine equivalents daily (MED).Strong 7.For patients beginning opioid therapy, evidence suggests limiting the first prescribed dose to less than 50 mg MED to reduce risk of nonfatal overdose or deaths.Weak 8.There is evidence to suggest that cyclical prescription to other opioids may mediate dose reduction in patients who have persistent pain despite using opioids.Weak 9.For those consuming more than 90 mg MED, there is evidence to support tapering opioids to the lowest effective dose with the aim of opioid cessation, if possible, rather than maintaining a consistent regimen.Weak 10.There is strong evidence to suggest the use of a formal multidisciplinary program for opioid-consuming patients encountering serious challenges in tapering.

Strong
work in an IPTC vs a unimodal treatment model (68% vs 32%). 23nterestingly, a study by Okifuji et al (1999) found a significant decline in the number of patients using opioids post-IPTC therapy in comparison to consumption at the time of program enrollment from 65% to 20%. 26ultidisciplinary approach to pain management has been recommended as a treatment modality by the International Association for the Study of Pain in addition to several Canadian provincial Colleges of Physicians and Surgeons. 27,28Currently, multidisciplinary chronic pain centres are limited to urban areas, leaving sub-urban and rural areas with poor accessibility.In conjunction with holistic pain management practices, the issue of illicit use of opioids also needs to be addressed.Access to harm reduction services, including supervised consumption sites and overdose prevention programs, will be instrumental to improve unsafe injection practices, reduce overdose morbidity and mortality, and facilitate detoxification and addiction treatment. 29mmary As opioid-related morbidity and mortality increases in Canada, addressing this public health crisis will be paramount for individual and societal health.While clinical guidelines have been updated to advise best-practice prescribing behaviours, multi-pronged systemic approaches will be key to tackle the complex roots of the opioid epidemic.Interdisciplinary treatment modalities for pain management have provided considerable evidence not only for pain reduction, but also for improved physical functioning, psychosocial wellbeing, and quality of life.Harm reduction programs should also be established across the nation to mitigate adverse health outcomes of substance abuse and addiction.Physicians are at the front-line of the opioid crisis and as such, have an onus to their patients to advocate for such systemic changes to address pain management in a holistic, patient-centered approach and provide meaningful solutions to end Canada's epidemic of opioid abuse.