This article was first published in the June 2017 edition of Drug and Alcohol Research Connections.
- There is increasing concern about the appropriateness of prescribing pharmaceutical opioids for patients with chronic non-cancer pain, given the risks of problematic use and dependence.
- Data were obtained from a national sample of 1424 people across Australia (median age, 58 years; 55% female; and experiencing pain for a median of 10 years), who had been prescribed opioids for chronic non-cancer pain.
- Current opioid consumption varied widely: 8.8% were taking <20 mg oral morphine equivalent (OME) daily, 52.1% were taking 21 to 90 mg OME daily, 24.3% were taking 91 to 199 mg OME daily and 14.8% were taking ≥200 mg OME daily.
- Greater daily OME consumption was associated with higher odds of multiple physical and mental health issues, aberrant opioid use, problems associated with opioid medication and opioid dependence.
- A significant minority (8.5%) met International Classification of Diseases, tenth edition (ICD-10) criteria for lifetime pharmaceutical opioid dependence and 4.7% met criteria for past-year ICD-10 pharmaceutical opioid dependence.
- Multivariate analysis found past-year dependence was independently associated with being younger, exhibiting more aberrant behaviours and having a history of benzodiazepine dependence.
Chronic non-cancer pain is common and burdensome. In 2010, low-back pain, neck pain and migraines were the first, fourth and eighth largest contributors respectively to the global nonfatal health burden (years lived with disability) (1). Chronic non-cancer pain has a major impact on the patient in terms of quality of life, mental health, health status, relationships and employment (2, 3).
Despite limited evidence of efficacy, there has been a considerable increase in the long-term prescribing of opioids for chronic non-cancer pain in several countries (4-8). There has also been professional and public concern about concomitant increases in problematic opioid use and harms, including dependence (4, 7, 9, 10).
Data on the patterns of opioid prescribing and related harms for individual patients over the longer term are limited (9). Clinical trials typically find far lower rates of aberrant drug-related behaviours and opioid dependence than have been reported in some observational studies, because controlled trials often exclude more complex patients and rarely follow up patients for long enough to capture behaviours indicative of abuse or dependence (9, 11). Physicians, specialists and academics have repeatedly called for better quality studies to contribute to understanding the nature and extent of opioid dependence in people prescribed opioids for chronic non-cancer pain.
THE POINT STUDY
The Pain and Opioid IN Treatment (POINT) cohort study was designed to document patterns of pharmaceutical opioid prescribing for, and risk of adverse events in, patients prescribed Schedule 8 opioids for chronic non-cancer pain (12). The study has received international recognition for its efforts to delineate issues related to opioid prescribing for patients with chronic non-cancer pain (13).
Participants were recruited through community pharmacies. We contacted 90% Of all community pharmacies across Australia; 33% agreed to assist with recruitment of the cohort. To check how similar our cohort might be to opioid patients overall, a random sample of 71 pharmacists were asked to collect data on the number and characteristics of all patients with chronic non-cancer pain patients who were prescribed opioids during their six-week recruitment window. We found that, of the total number of such patients having opioids supplied by these pharmacies, 52% were female (the POINT cohort was 55% female); and 7% were 18 to 34 years of age, 55% were 35 to 64 years and 38% were 65 years or older (vs 5%, 62% and 33%, respectively, in the POINT cohort). Of these patients, 63% were prescribed oxycodone (vs 62% in the POINT cohort), 16.5% were prescribed morphine (vs 15% in the POINT cohort), 21% fentanyl patches (vs 15% in the POINT cohort) and 24% buprenorphine patches (vs 21% in the POINT cohort). These findings suggest similarity between the POINT sample and people prescribed opioids for chronic non-cancer pain more generally.
Participant eligibility and recruitment
Participants were eligible if they were:
- 18 years of age or older
- fluent in English
- mentally and physically able to complete telephone and self-complete interviews
- without obvious cognitive impairment (determined by researchers at the time of obtaining consent)
- living with chronic non-cancer pain
- prescribed an opioid such as morphine, oxycodone or fentanyl (Schedule 8 in the Australian classification of drugs of dependence; namely, drugs that are subject to additional regulatory controls regarding manufacture, supply, distribution, possession and use20);
- more than 6 weeks into a course of taking such opioids for chronic non-cancer pain
A history of injecting drug use was not an exclusion criterion, but people currently prescribed methadone or buprenorphine as treatment for heroin dependence were not eligible. Patients taking opioids for cancer pain were also excluded.
Around 2700 participants were referred into the study. POINT staff determined the eligibility of potential participants. The 2091 eligible participants then underwent a voluntary informed consent process. The 1873 people who were willing to participate underwent an initial telephone interview that took about one to one-and-a-half hours. Eighty-one percent of those who were eligible (1514 participants) completed the baseline interview
EARLY FINDINGS FROM THE POINT STUDY
The POINT study has found that people who have been prescribed strong opioids for chronic non-cancer pain have very complex demographic and clinical profiles (14). Overall, participants reported a low rate of employment, and most were on low weekly in-comes similar to the amounts for aged or disability pensions. About two-thirds of participants reported that their pain had impacted on their employment status. Additionally, one-in-six reported some barriers to pain treatment and one-third reported that they were unable to afford non-opioid prescription pain treatments. Our findings are consistent with other research that suggests chronic non-cancer pain has a major impact on the ability to work, and patients with chronic noncancer pain experience significant socioeconomic disadvantage (15).
Demonstrating the complexity of the cohort, most participants experienced multiple pain conditions, reported poor physical health and had experienced childhood abuse or neglect. Just under half met criteria for current moderate to severe depression. Substantial minorities among participants met criteria for current moderate to severe anxiety or agoraphobia, reported attempted suicide, and reported alcohol or cannabis use disorder (International Classification of Diseases, tenth edition [ICD-10] criteria).
Complex clinical profiles were more prevalent among the younger age groups. These groups reported more mental health problems, more experience of childhood abuse or neglect and lifetime suicidality, and more substance use than the older age groups. Younger participants were prescribed higher doses of opioids, were more likely to also be prescribed codeine, and were likely to be taking concurrently prescribed benzodiazepines, or antidepressant or antipsychotic medications. Taken together, these characteristics suggest a very high-risk group, with multiple concomitant risk factors for overdose due to polypharmacy (16, 17). Although diversion and injection prevalence were low among POINT participants, the younger age groups were more likely to engage in non-adherent behaviours. A more detailed examination of diversion in the POINT cohort has been published previously (18).
This complex picture highlights the need for greater recognition of the social and psychological contributions to the experience of chronic non-cancer pain and also indicates the need for multifaceted (and multidisciplinary) health care approaches that address the numerous comorbidities seen in people with chronic non-cancer pain
Universal precautions in opioid prescribing have been widely endorsed internationally and in Australian national guidelines, and provide a uniform approach to risk management based on the fact that chronic pain and substance use disorders often co-occur (19-21). Guidelines based on universal precautions often suggest consultation with a pain specialist for patients in whom high doses (usually more than 91 mg oral morphine equivalent [OME] daily) appear to be required and in whom improvement in pain and function are not seen (20). Uptake of these guidelines in practice is generally low, possibly because of challenges in prescriber confidence in managing identified risks.
The POINT study provides a unique perspective, reporting on actual consumption of all pharmaceutical opioids, including those obtained without prescription, i.e. over-the-counter opioids sold in pharmacies. Participants record all medications they consume in a seven-day medication diary that includes dosages.
This detailed assessment revealed some concerning patterns of opioid consumption, and clear associations between high-level consumption and a range of indicators of poorer functioning. About 15% of the cohort were taking daily doses of more than 200 mg OME, and around 40% of the cohort were consuming 90 mg OME or more daily. Those taking higher doses had the highest rates of problems associated with opioid medication, such as aberrant behaviours and opioid dependence. Of concern, participants taking higher OME doses (greater than 90 mg OME daily) reported less pain relief from their medications than participants taking lower doses.
Higher current opioid consumption was associated with a range of demographic (being younger, male and unemployed) and substance use characteristics (lifetime alcohol and substance use disorders and past month use of alcohol and illicit drugs). Correlates of higher opioid consumption were also consistent with factors identified in the literature as being associated with increased overdose mortality risk, including young age, male sex, lower socioeconomic status and psychiatric comorbidity (22, 23). They were also consistent with characteristics identified in risk screening tools for opioid prescribing (24).
The association of higher opioid consumption with increasing levels of aberrant behaviours (e.g. tampering and nonmedical use) suggests that monitoring by prescribers is warranted (25). Conversely, the finding that some behaviours such as doctor shopping were rarely reported suggests that, at least in this sample, strategies such as prescription drug monitoring would provide limited ability for identifying patients at risk.
Pharmaceutical opioid dependence
A minority (8.5%) of participants met criteria for lifetime ICD-10 pharmaceutical opioid dependence, and 4.7% had features of dependence within the past year. The median age of onset for ICD-10 opioid use disorder was 40 years (interquartile range, 32-49 years) (26). This is consistent with research suggesting that pharmaceutical opioid use disorders affect a minority of patients with chronic non-cancer pain who are prescribed opioids. In this study, past-year dependence was associated with many indicators of adverse psychosocial, mental and physical functioning, including younger age, unemployment, mental health problems and a history of substance use and dependence. Those who met criteria for past-year opioid dependence were also currently prescribed a higher median opioid consumption, reported more problems and concerns associated with their opioid use and were also more likely to engage in aberrant behaviours. The most common aberrant behaviours among participants who met criteria for dependence were asking for an early prescription renewal (33 participants; 48.5%), and asking the doctor for an increase in dose (27 participants; 39.7%,). Past-year opioid dependence was independently associated with being younger and having lifetime benzodiazepine dependence, which has important clinical implications for the safety of opioid prescribing.
The term ‘adverse selection’ has been coined to describe this apparent contradiction in which the likelihood of a patient receiving opioid therapy, and at greater doses, increases as the number of risk factors for adverse outcomes increases (22). The POINT study found strong evidence for this, whereby participants consuming higher levels of opioids were clearly those with a more complex picture of physical and mental health problems, as well as social disadvantage. Further, in this sample many of the chronic non-cancer pain patients prescribed higher doses of long-term opioids were concurrently taking other medications (e.g. benzodiazepines) in doses that are considered high-risk for adverse outcomes, and levels of concomitant medications were higher among participants taking higher amounts of opioids.
The POINT study has clearly demonstrated the complex nature of patients with chronic non-cancer pain, involving multiple sociodemographic, physical and mental health problems. A significant proportion of patients with chronic non-cancer pain taking very high doses of opioids had multiple risk factors for potential adverse outcomes, such as dependence and overdose. Similarly, patients meeting criteria for dependence had higher levels of most indicators of poorer wellbeing. Higher opioid consumption was also strongly associated with risk for dependence; and patients on higher opioid doses had a different clinical profile compared with those on lower doses. There is clearly a need for increased vigilance and reassessment of the progress and functioning of patients with chronic non-cancer pain in whom opioid consumption is considerable and problems related to opioid consumption are prominent.
Many patients with chronic non-cancer pain are treated in primary care. Education and training of primary care physicians in chronic non-cancer pain and addiction medicine is crucial; the risks of high-dose consumption of pharmaceutical opioids need to be weighed against clinical evidence that patients are deriving net benefit from their use. It is crucial for primary care physicians to routinely collect detailed histories of their patients in order to determine the most appropriate treatment plan, and to consider involving specialist mental health, addiction or other services when appropriate and available.
Much of the material presented in this article is based on the following publications:
- Campbell, G., Nielsen, S., Bruno, R., Lintzeris, N., Cohen, M., Hall, W., Larance, B., Mattick, R.P., & Degenhardt, L. (2015). The Pain and Opioids IN Treatment (POINT) study: Characteristics of a cohort using opioids to manage chronic non-cancer pain. Pain 156(2), 231-242.
- Campbell, G., Nielsen, S., Bruno, R., Larance, B., Smith, K., Hall, W., Cohen, M., & Lintzeris, N., & Degenhardt, L., (2015). Pharmaceutical Opioid Use and Dependence among People Living with Chronic Pain: Associations Observed within the Pain and Opioids in Treatment (POINT) Cohort. Pain Medicine 16(9), 1745-1758.
1. Vos T, Barber RM, Bell B, Bertozzi-Villa A, Biryukov S, Bolliger I, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990 to 2013;2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet. 2016;386(9995):743-800.
2. Blyth FM, March LM, Brnabic AJM, Jorm LR, Williamson M, Cousins MJ. Chronic pain in Australia: a prevalence study. Pain. 2001;89(2–3):127-34.
3. Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006;10(4):287-333.
4. Compton WM, Volkow ND. Major increases in opioid analgesic abuse in the United States: concerns and strategies. Drug Alcohol Depend. 2006;81(2):103-7.
5. Degenhardt L, Black E, Breen C, Bruno R. Trends in morphine prescriptions, illicit morphine use and associated harms among regular injecting drug users in Australia. Drug and Alcohol Review. 2006;25(5):403-12.
6. Dhalla IA, Mamdani MM, Sivilotti ML, Kopp A, Qureshi O, Juurlink DN. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone. CMAJ Canadian Medical Association Journal. 2009;181(12):891-6.
7. Leong M, Murnion B, Haber PS. Examination of opioid prescribing in Australia from 1992 to 2007. Internal Medicine Journal. 2009;39(10):676-81.
8. Roxburgh A, Bruno R, Larance B, Burns L. Prescription of opioid analgesics and related harms in Australia: Medical Journal of Australia. 195 (5) (pp 280-284), 2011. Date of Publication: 5 September 2011.
9. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, et al. The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain: A Systematic Review for a National Institutes of Health Pathways to Prevention WorkshopEffectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain. Annals of Internal Medicine. 2015;162(4):276-86.
10. Fischer B, Argento E. Prescription opioid related misuse, harms, diversion and interventions in Canada: a review. Pain Physician. 2012;15(3 Suppl):ES191-203.
11. Chou R, Ballantyne JC, Fanciullo GJ, Fine PG, Miaskowski C. Research gaps on use of opioids for chronic noncancer pain: findings from a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. The Journal of Pain. 2009;10(2):147-59. e15.
12. Campbell G, Mattick R, Bruno R, Larance B, Nielsen S, Cohen M, et al. Cohort protocol paper: the Pain and Opioids In Treatment (POINT) study. BMC pharmacology & toxicology. 2014;15(1):17.
13. Ballantyne JC. What can the POINT study tell us? Pain. 2015;156(2):201-2.
14. Campbell G, Nielsen S, Bruno R, Lintzeris N, Cohen M, Hall W, et al. The Pain and Opioids IN Treatment study: characteristics of a cohort using opioids to manage chronic non-cancer pain. Pain. 2015;156(2):231-42.
15. Rogers KD, Kemp A, McLachlan AJ, Blyth F. Adverse Selection? A Multi-Dimensional Profile of People Dispensed Opioid Analgesics for Persistent Non-Cancer Pain. PloS one. 2013;8(12):e80095.
16. Jones CM, Mack KA, Paulozzi LJ. Pharmaceutical overdose deaths, United States, 2010. Jama. 2013;309(7):657-9.
17. Nielsen S, Lintzeris N, Bruno R, Campbell G, Larance B, Hall W, et al. Benzodiazepine use amongst chronic pain patients prescribed opioids: associations with pain, physical and mental health and health service utilization. Pain Medicine. 2015;doi: 10.1111/pme.12594.
18. Belcher J, Nielsen S, Campbell G, Bruno R, Hoban B, Larance B, et al. Diversion of prescribed opioids by people living with chronic pain: results from an Australian community sample. Drug Alcohol Rev. 2014;33(1):27-32.
19. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Medicine. 2005;6 (2):107-12.
20. Manchikanti L, Abdi S, Atluri S, Balog CC, Benyamin RM, Boswell MV, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance. Pain Physician. 2012;15(3 Suppl):S67-116.
21. Royal Australasian College of Physicians. Prescription Opioid Policy: Improving management of chronic non-malignant pain and prevention of problems associated with prescription opioid use. Sydney Royal Australasian College of Physicians; 2009.
22. Sullivan MD. Who gets high-dose opioid therapy for chronic non-cancer pain? PAIN®. 2010;151(3):567-8.
23. Sullivan MD, Howe CQ. Opioid therapy for chronic pain in the United States: promises and perils. PAIN®. 2013;154:S94-S100.
24. Webster L, Webster R. Predicting Aberrant Behaviors in Opioid Treated Patients: Preliminary Validation of the Opioid Risk Tool. Pain Medicine. 2005;6(6):432-42.
25. Passik SD, Kirsh KL. The Interface Between Pain and Drug Abuse and the Evolution of Strategies to Optimize Pain Management While Minimizing Drug Abuse. Experimental and Clinical Psychopharmacology. 2008;16 (5):400-4.
26. Campbell G, Nielsen S, Larance B, Bruno R, Mattick R, Hall W, et al. Pharmaceutical Opioid Use and Dependence among People Living with Chronic Pain: Associations Observed within the Pain and Opioids in Treatment (POINT) Cohort. Pain Medicine. 2015;16(9):1745-58.