1. The use and unintended consequences of pharmaceutical opioids in Australia?
Michael Farrell

2. Disclosures
Mundipharma Australia (who market Reformulated OxyContin® and Targin®) provided travel support for this meeting.
The NOMAD study was funded via an investigator-driven, untied educational grant from Mundipharma Australia. The funder has no role in the design, conduct, analysis, interpretation or decision of what/where to publish.
I have also received untied educational grants for post-marketing surveillance of new opioid substitution therapy medications by Reckitt Benckiser, also conducted without any involvement of RB in the design, conduct, analysis or publication of findings.

3. Overview Utilisation of pharmaceutical opioids
What unintended consequences are causing concern?
People with chronic non-cancer pain using opioids
Use of Fentanyl by PWID in Australia

4. 1. Utilisation of pharmaceutical opioids

5. Availability of opioids for pain management (2011-13)
Berterame et al (2016) Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. The Lancet.

6. Australia: PBS opioid dispensings
15-fold increase in dispensings processed,
Issues:
Opioids costing less than co-payment threshold
Authorities
Private scripts
Non-PBS listed opioids
Non-prescribed (OTC) opioids
Dispensing ≠ consumption
There have been considerable increases in prescribing of opioids: a 15-fold overall increase in PBS-subsidised opioid dispensings between
Blanch et al (2014). An overview of the patterns of prescription opioid use, costs and related harms in Australia. BJ Clinical Pharmacology.

7. The picture in 2013: PBS opioid dispensings vs
The picture in 2013: PBS opioid dispensings vs. prescription opioid unit sales
Strong opioids : morphine, oxycodone, buprenorphine patch, methadone tablet, fentanyl, hydromorphone
Other prescribed opioids : prescription codeine, dextropropoxyphene, tramadol, tapentadol
Over-the-counter opioids : codeine products available at pharmacies without a doctor’s prescription

8. What does opioid consumption look like?
It’s clearly increasing
Reliance on aggregate PBS statistics will lead to a likely underestimation of consumption: OTC consumption is considerable
Consumption higher in rural and regional areas and areas with more disadvantage
Need analyses of person-level data to examine (i) whether this is a problem, and (ii) how much of this is a problem
AND we need direct data on patterns of consumption (e.g. POINT and NOMAD study)

9. 2. Unintended consequences of opioid use

10. Concerns accompanying opioid use
Non-adherent use
Stockpiling
Doctor shopping
Tampering
Diversion
Diversion to others
Use of someone else’s medication
Dependence
Overdose
Larance et al (2011) Definitions related to the use of pharmaceutical opioids:  Extra-medical use, diversion, non-adherence and aberrant drug behaviours. Drug and Alcohol Review, 30, 236–245.

11. Changing nature of opioid-related deaths
Over the period of monitoring…
Source: National Coronial Information System (NCIS); Roxburgh et al (MJA, 2011); Roxburgh et al (2013)

12. Not everyone is at similar risk for adverse outcomes
Potential risk factors for poorer clinical outcomes:
Mental health problems
History of drug and alcohol use problems
Experience of trauma
More complex pain problems
Other illnesses and disabilities
Other medications
Not everyone is at similar risk for adverse outcomes

13. 3. People living with chronic non-cancer pain and using opioids

14. Background Chronic non-cancer pain (CNCP) is a common complaint
CNCP has a major impact on quality of life, mental health, health status, relationships and employment
There have been considerable increases in prescribing of opioids for CNCP
Concern about harms related to pharmaceutical opioids
Will there be greater problems with opioid dependence?
Will there be considerable diversion of these medications?
Is long-term use of opioids for chronic pain effective?

15. POINT cohort study design
Sample: people living with chronic non-cancer pain, prescribed opioids >=6 weeks
Recruitment across community pharmacies in Australia, with Pharmacy Guild support:
Contacted 93% (n=5,332) of all community pharmacies in Australia via fax and phone
33% of pharmacies agreed to be involved in recruitment
Four assessment waves:
Baseline n = 1,514
T2 follow up (3 months) 82% follow-up
T3 follow up (12 months) 83% follow-up
T4 follow up (24 months) 83% follow-up
Permission to obtain medical records from Medicare for access to Medicare claim history and prescription history as well as other health records
Campbell et al (2014). Cohort protocol: The Pain and Opioids IN Treatment (POINT) study. BMC Pharmacol & Toxicol. 15

16. Pain and treatment experience
Median time experiencing pain
10 years
Median time to opioid prescription after pain onset
12 months
On some type of opioid continuously (Median)
4 years
More than one pain condition
85%
Median pain conditions in the previous year 3
Back or neck problems (most common condition)
76%
Median other chronic physical health problems 1
Campbell et al (2015). The Pain and Opioids IN Treatment (POINT) study: Characteristics of a cohort using opioids to manage chronic non-cancer pain. Pain.

17. Current mental disorders
Campbell et al (2015). The Pain and Opioids IN Treatment (POINT) study: Characteristics of a cohort using opioids to manage chronic non-cancer pain. Pain.

18. Prescription opioid use in the POINT cohort
Prescribed opioids for a median of 4 years
20% currently prescribed ≥2 Schedule 8 opioids
63% also taking over-the-counter opioids
Median oral morphine equivalent (OME) mg per day – 75mg
15% taking over 200 OME per day
Campbell et al (2015). Correlates of pharmaceutical opioid use and dependence among people living with chronic pain: Findings from the Pain and Opioids IN Treatment (POINT) study. Pain Medicine 18

19. Problematic use of pharmaceutical opioids19

20. Dependence in POINT cohort (ICD-10)
One in twelve (8.5%) met lifetime ICD-10 criteria for pharmaceutical opioid dependence
One in ten (10.1%) met criteria ICD-10 criteria for harmful use
One in five (18.6%) met lifetime criteria for ICD-10 pharmaceutical opioid use disorder
One in twenty (5%) were dependent in the past year
Younger, more likely to engage in non-adherent behaviours, history of benzodiazepine dependence
All scored intermediate-to-high on Prescribed Opioids Difficulties Scale
Campbell et al (2015). Correlates of pharmaceutical opioid use and dependence among people living with chronic pain: Findings from the Pain and Opioids IN Treatment (POINT) study. Pain Medicine 20

21. Indicators of problematic use, by dose
*** ** **
*** ** **
Efficacy
Campbell et al (2015). Correlates of pharmaceutical opioid use and dependence among people living with chronic pain: Findings from the Pain and Opioids IN Treatment (POINT) study. Pain Medicine 21

22. Trends in Fentanyl injecting and deaths in Australia

23. Opioid Use in Australia Heroin and Pharmaceutical opioid injecting
Source: Illicit Drug Reporting System

24. Results: Fentanyl injected on site 2012 to 2017

25. Pharmaceutical opioid deaths (by opioid) per million population
Source: NCIS; Roxburgh et al, Drug and Alcohol Dependence 2017

26. Acknowledgements
Thanks to our participants in all the studies mentioned here
Collaborators : Louisa Degenhardt, Gabrielle Campbell, Amanda Roxburgh, Natasa Gisev, Suzi Nielsen, Sarah Larney, Elena Cama, Wayne Hall, Nicholas Lintzeris, Richard Mattick, Raimondo Bruno, Amy Peacock, Milton Cohen, Robert Ali, Nancy White, Timothy Dobbins, Lucy Burns, Adrian Dunlop, Michael Farrell, Fiona Shand
Advisory Committee (POINT): Fiona Blyth, Lesley Brydon, Elizabeth Carrigan, Malcolm Dobbin, Julia Fleming, Roger Goucke, Simon Holliday, Denis Leahy, Andrea Mant, Jake Najman, Milana Votrubec, Jason White
Associate Investigators and Advisory Committee (NOMAD): Lesley Brydon, Gabrielle Campbell, Apo Demirkol, Malcolm Dobbin, Adrian Dunlop, Angella Duvnjak, Paul Haber, Marianne Jauncey, Robert Kemp, Richard Mattick, Suzanne Nielsen, Amy Peacock, Nghi Phung, Ann Roche, Nancy White and Hester Wilson
POINT study team: Gabrielle Campbell (coordinator), Bianca Hoban, Kimberley Smith, Ranira Moodley, Sarah Freckleton, Rachel Urquhart-Secord, Teleri Moore, Courtney O’Donnell
NOMAD study team : Ivana Kihas, Toni Hordern, Amy Peacock, Nancy White, Elena Cama, Dominic Oen, Oluwadamisola and our team of interviewers
NHMRC project grant: # (POINT study)
NHMRC fellowships: Briony Larance, Louisa Degenhardt, Suzanne Nielsen, Richard Mattick
Mundipharma: Untied educational grant; Billy Henderson
Pharmacy Guild of Australia

27. Thank you! Louisa Degenhardt Gabrielle Campbell Briony Larance
Amanda Roxborough
Research Fellow (NHMRC ECF)
NDARC, UNSW Australia
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