title: Mortality risk of opioid substitution therapy with methadone versus buprenorphine: a retrospective cohort study.
abstract: BACKGROUND
  Opioid dependence increases risk of premature mortality. Opioid substitution therapy with methadone or buprenorphine reduces mortality risk, especially for drug-related overdose. Clinical guidelines recommend methadone as the first line of opioid substitution therapy. We aimed to test whether buprenorphine treatment has a lower mortality risk than does methadone treatment by comparing all-cause mortality and drug-related overdose mortality at treatment induction, after in-treatment medication switches, and following treatment cessation.
  
  
  METHODS
  We did a retrospective cohort study of all patients with opioid dependency (n=32,033) in New South Wales, Australia, who started a methadone or buprenorphine treatment episode from Aug 1, 2001, to Dec 31, 2010, including 190,232·6 person-years of follow-up. We compared crude mortality rates (CMRs) for all-cause and drug-related overdose mortality, and mortality rate ratios (MRRs) according to age, sex, period in or out of treatment, medication type, and in-treatment switching.
  
  
  RESULTS
  Patients who initiated with buprenorphine had reduced all-cause and drug-related mortality during the first 4 weeks of treatment compared with those who initiated with methadone (adjusted all-cause MRR 2·17, 95% CI 1·29-3·67; adjusted drug-related MRR 4·88, 1·73-13·69). For the remaining time on treatment, drug-related mortality risk did not differ (adjusted MRR 1·18, 95% CI 0·89-1·56), but weak evidence suggested that all-cause mortality was lower for buprenorphine than methadone (1·66, 1·40-1·96). In the 4 weeks after treatment cessation, all-cause mortality did not differ, but drug-related mortality was lower for methadone (adjusted all-cause MRR 1·12, 0·79-1·59; adjusted drug-related MRR 0·50, 0·29-0·86). Patients who switched from buprenorphine to methadone during treatment had lower mortality in the first 4 weeks of methadone treatment than matched controls who received methadone only (CMR difference 7·1 per 1000 person-years, 95% CI 0·1-14·0); no mortality difference was noted for switches from buprenorphine to methadone or for switches to either medication beyond the first 4 weeks of treatment.
  
  
  CONCLUSIONS
  In a setting with high risk of death in the first 4 weeks of opioid substitution therapy, buprenorphine seemed to reduce mortality in this period, but little difference between buprenorphine and methadone was noted thereafter or for in-treatment switching of medications. Cross-cohort corroboration of our findings and further assessment of the stepped treatment model is warranted.
  
  
  BACKGROUND
  Australian National Health & Medical Research Council.
authors.affiliation: National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia; Addictions Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. Electronic address: j.kimber@unsw.edu.au.
authors.forename: Jo
authors.initials: J
authors.lastname: Kimber
authors.affiliation: National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia; Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Larney
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hickman
authors.affiliation: Centre for Big Data Research, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Randall
authors.affiliation: National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia; School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Louisa
authors.initials: L
authors.lastname: Degenhardt
mesh_terms: D000328:Adult; D002047:Buprenorphine / Q000009:adverse effects*; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008691:Methadone / Q000009:adverse effects*; D008875:Middle Aged; D009026:Mortality; D058850:Opiate Substitution Treatment / Q000009:adverse effects*; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D002047:Buprenorphine; D008691:Methadone