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Impact of Buprenorphine and Methadone on Mortality: Primary Care Cohort Study in the UK

This study examines the relative mortality risk for individuals prescribed buprenorphine or methadone for opioid substitution treatment (OST) in UK primary care. It investigates whether buprenorphine reduces mortality risk during treatment compared to methadone and whether buprenorphine could potentially reduce drug-related deaths in the population.

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Impact of Buprenorphine and Methadone on Mortality: Primary Care Cohort Study in the UK

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  1. The impact of buprenorphine and methadone on mortality: a primary care cohort study in the United Kingdom Matthew Hickman, Colin Steer, Kate Tilling, Aaron Lim, John Marsden, Tim Millar, John Strang, Maggie Telfer, Peter Vickerman, John Macleod

  2. http://www.imperial.ac.uk/medicine/mrc-addiction-research-clinical-training/http://www.imperial.ac.uk/medicine/mrc-addiction-research-clinical-training/ marc@imperial.ac.uk

  3. Acknowledgements The study was supported by NIHR HS&DR Project: 12/136/105 - Evaluating the impact of opiate substitution treatment on drug related deaths in the population: a natural experiment using primary care, other drug treatment databases & model projections. ISAC CPRD Protocol 14_073R2. NIHR Health Protection Research Unit (HPRU) in Evaluation NIHR School of Public Health Research The funder had no role in study design, data collection, the analysis and interpretation, or the writing of this report. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health

  4. Trends in drug related deaths driven by heroin/opioids – and increasing

  5. Clinical Practice Research Datalink (CPRD) • ~ 674 UK practices, > 11 million patients • 7% (& broadly representative) of UK population • Drop patients prescribed bup/meth for pain relief • Daily minimum dose criteria of 20mg methadone, 4mg buprenorphine • Follow-up censored 1 year after each script • 606 GP practices had 1 OST patient • 352/395 practices in England linked to ONS data. UK Study Data

  6. Flow Diagram: CPRD Extract and Cohort Risk Set - patients prescribed methadone or buprenorphine for OST 1998-July 2014 • 11,033 patients • 30,410 py • 26,546 OST • 17,373 (61%) meth • 9,173 (39%) bup • 5,935 patients DRP • 16,363 py • 9,550 meth • 6,050 bup

  7. Aims/ Ho • Examine relative mortality risk for people prescribed methadone or buprenorphine for OST in UK primary care • Does buprenorphine reduce mortality risk during treatment compared to methadone? • Could buprenorphine reduce the number of drug related deaths in the population?

  8. Differences in mortality risk during and after OST Propensity score IPW (age, sex, comorbidity, year, benzo, gabapentoid, self-harm, overdose, alcohol problems, prison, homeless, OST patients in practice, Practice size. And adjusted for period * OST, age*x OST, comorbidity*OST. MR unadjusted mortality rates weighted using IPW

  9. OST modality x Treatment Period Propensity score IPW (age, sex, comorbidity, year, benzo, gabapentoid, self-harm, overdose, alcohol problems, prison, homeless, OST patients in practice, Practice size. And adjusted for period * OST, age*x OST, comorbidity*OST. MR unadjusted mortality rates weighted using IPW

  10. Evidence of Confounding • Buprenoprhine • varies by region, calendar period, practice size • ↑ women, older, co-morbid patients • ↓ co-prescribed benzodiazepines, reported history of self-harm, overdose, alcohol problems, imprisonment, and homelessness • Drug Related Poisoning • Associated with gender, co-morbidity, co-prescribed benzodiazepines, self-harm, overdose, alcohol problems, imprisonment, and homelessness

  11. IRR comparing mortality risk for patients on buprenorphine or methadone by period on and off treatment The figure shows the risk of mortality for buprenorphine relative to methadone for the four treatment periods unadjusted and adjusted, propensity score based weighted analyses (IPW), adjustment for interactions of OST with age or comorbidity. Incident rate ratios are shown on a log scale with 95% CIs.

  12. IRR comparing mortality risk for patients on buprenorphine or methadone by period on and off treatment The figure shows the risk of mortality for buprenorphine relative to methadone for the four treatment periods unadjusted and adjusted, propensity score based weighted analyses (IPW), adjustment for interactions of OST with age or comorbidity. Incident rate ratios are shown on a log scale with 95% CIs.

  13. Interaction OST Modality with Co-morbidity & Age

  14. Average duration OST • Highly skewed distribution • Buprenorphine shorter than Methadone • Mean (and median) • 363 (111) methadone • 173 (40) for buprenorphine

  15. DRP Weighted Mortality Risk & probability that DRP deaths would reduce in the population for patients on Methadone/Buprenorphine vs no OST (and assuming 50% or all patients switch from buprenorphine to methadone after 4 weeks) vs no OST

  16. Implications for practice • Evidence support Ho that buprenorphine safer than methadone at treatment initiation • But residual confounding/ confounding by indication possible • Replicate analyses/ cross cohort/country comparison • Beneficial effects of buprenorphine on mortality risk after treatment less clear • Shorter treatment for buprenorphine so may offset benefits • Experimental evidence needed on:- • how to combine bup/meth to reduce mortality risk • retain people in OST so that deaths in population fall • Stratified/ personalised OST

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