Etat des lieux des traitements méthadone et buprénorphine A/Prof Adrian Dunlop Biarritz 2015
Summary Methadone and buprenorphine in Australia Comparing treatments Effectiveness Australian studies Mortality in treatment Causes of death Diversion of medication No treatment?
Australian opiate treatment system Methadone 1969, buprenorphine 2000 Buprenorphine-naloxone 2006 (film 2011) Expanded to prevent HIV in IDU Methadone & buprenorphine treatment delivered together Specialist Clinics (20%) General practice & community pharmacy (80%) Relatively accessible & affordable Costs to patient ~ 1500/patient/year
50000 45000 40000 35000 30000 25000 20000 15000 10000 5000 0 Number of patients on methadone/buprenorphine in Australia Rate ~210/100,000 population AIHW 2015
Methadone & buprenorphine Licence required for all doctors to prescribe Medication - choice of patient/doctor 67% methadone 33% buprenorphine Mainly supervised dosing methadone & buprenorphine Treatment Heroin>>prescription opioids (oxycodone, morphine ) Co-infection HIV ~1% HCV PCR + ~50%
Comparison methadone & buprenorphine
Methadone & buprenorphine both effective substitution treatment Buprenorphine equivalent to methadone at higher doses Reducing heroin use & retention Buprenorphine Mattick Cochrane 2014 flexible dose studies - retention lower RR 0.83 (0.73-0.95) Low buprenorphine doses/induction too slow/easier to cease?
Data linkage studies Retrospective design Using large datasets e.g. All people on methadone, buprenorphine Advantages Explore uncommon events often don t occur during RCTs due to time period statistical power Disadvantages Non experimental design (bias)
Retrospective cohort (data linkage study) 10 years 2001-2010 n=32,000 on methadone or buprenorphine in NSW 190,232 patient/years follow up Crude mortality rates Lancet Psychiatry 2015
Implications First 4 weeks of treatment Deaths methadone > buprenorphine (Not if switch from buprenorphine to methadone) Rest of treatment Deaths methadone = deaths buprenorphine No change if switch (either way) Caution regarding methadone inductions
Mortality after treatment Degenhardt DAD 2009
Cycling of treatment NSW Australia Burns Addiction 2009
Addiction 2014 Retrospective cohort study (data linkage) 20 years 1985-2005 n=43,789 on methadone or buprenorphine 412,216 patient-years, median follow up 8.7 years 3685 deaths
Mortality among opioid dependent Overdose is the most common cause 43% opioid 9% other drugs Suicide is the next single largest cause of death 13% Liver-related 7% people in NSW Accidental opioid-related Liver-related Transport accidents Cancer Other Suicide, not drug-related Other drug-related Cardiovascular HIV/AIDS Degenhardt et al (2014). Causes of death in a cohort treated for opioid dependence between 1985-2005. Addiction 16
Deaths of patients on methadone & buprenorphine 88% deaths avoidable Mainly overdose, suicide, car crash Liver-related, cardiovascular, cancer Years of potential life lost Average years life lost 44/person (29 before age 65) Conclusion Despite methadone and buprenorphine, many lives lost
Retention in treatment Addiction 2015 Retrospective cohort (Data linkage study) 10 years 2001-2010 First time entrants in opiate treatment n=15600 54% methadone, 46% buprenorphine
Retention in treatment methadone buprenorphine
Buprenorphine, more treatment episodes
Buprenorphine, more switches
Diversion/injection DAD 2011 Multiple data sources Sales of methadone & buprenorphine Surveys: PWID n=900, patient on meth & bup n=440 Estimates prevalence injecting (adjusting for availability methadone & buprenorphine)
Any injection
Diversion Buprenorphine injection/diversion more common compared to methadone & buprenorphine-naloxone Diverted past 6 months Self injected past 6 months Buprenorphine 5% 10% Buprenorphinenaloxone 1% 5% Methadone 2% 5%
What happens with no treatment? Buprenorphine-naloxone wait list RCT RCT n=51 Patients entering treatment 12 weeks randomised to wait list/buprenorphine-naloxone (flexible dose, target 16 mg) Clinical & health economic outcomes Dunlop, in preparation
Mean (95% CI) number Mean of days (95% of CI) number of days of heroin use in the previous heroin 28 use days in the previous 28 days 0 7 0 14 7 21 14 28 21 28 Mean (95% CI) number of days of heroin use in the previous 28 days 0 7 14 21 28 Mean (95% CI) number of days of heroin use in the previous 28 days 0 7 14 21 28 0 M he Heroin use self report *** BPX Treatment, Waitlist 0 28 Time since BPX Treatment, BPX Treatment, Waitlist Waitlist *** *** 0 28 56 84 Time since randomization (days) 0 28 56 84 Time since randomization (days) 0 0 28 28 56 56 84 84 Time since Time randomization since randomization (days) (days)
% Positive Urine drug screens % Positive UDS 6'mam/morphine 100 80 60 40 BNX WL 20 0 Screen D28 D56 D84 Days
Cost effectiveness Cost per heroin free day from the provision of buprenorphine-naloxone $A18.24 (95% CI 4.50, 28.49) A total 12 week reduction in adjusted costs including crime of $A5,722.42 (95% CI 3,299.42, 8,154.64) in favor of the treatment group
Clinical implications of this talk Methadone & buprenorphine Equally effective Risks of methadone induction Especially first month of treatment Caution in General Practice settings Preventable deaths common Especially overdose, suicide, liver-related How to provide enhanced treated to address these issues? Naloxone, management of depression, HBV, HCV treatment
Clinical implications II Higher doses of buprenorphine to improve retention E.g. 8 (4+4), 12, 16 mg How to improve retention? Buprenorphine-naloxone Less injection/diversion compared to buprenorphine/methadone Patient choice remains important in treatment Buprenorphine ~ methadone No treatment is expensive! (& dangerous)
Acknowledgements U Sydney: Nick Lintzeris, Suzi Nielsen, Paul Haber UNSW: Michael Farrell, Louisa Degenhardt, Briony Larance, Amanda Roxburgh, Lucy Burns, Jan Copeland, Nadine Ezard U Newcastle: Amanda Baker, Chris Dayas, Peter Stanwell, Amanda Brown, Geoff Isbister ANU: Rebecca McKetin Burnet Centre: Paul Dietze, Peter Higgs HNE Health: Susan Heyman, Vi Hunt, Craig Sadler, Sally McKenna, Martin Cohen, Michelle Hall, Rohan Holland, Elaine Murray Merci beaucoup!