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Marteau D, McDonald R, Patel K. 
“The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales”. 
BMJ Open. 2015 May 30;5(5):e007629.
OBJECTIVE: To examine the population-wide overdose risk emerging from the prescription of methadone and buprenorphine for opioid substitution treatment in England and Wales.

DESIGN: Retrospective administrative data study.

SETTING: National databases for England and Wales. PARTICIPANTS/CASES: Drug-related mortality data were drawn from the Office for National Statistics, and prescription data for methadone and buprenorphine were obtained from the National Health Service for the years 2007-2012. During this 6-year period, a total of 2366 methadone-related deaths and 52 buprenorphine-related deaths were registered, corresponding to 17,333,163 methadone and 2,602,374 buprenorphine prescriptions issued. The analysis encompassed poisoning deaths among members of the wider population of England and Wales who consumed, but were not prescribed these medications, in addition to patients prescribed methadone or buprenorphine. MAIN OUTCOME MEASURES: Mortality risk: substance-specific overdose rate per 1000 prescriptions issued; relative risk ratio of methadone in relation to buprenorphine.

RESULTS: During the years 2007-2012, the pooled overdose death rate was 0.137/1000 prescriptions of methadone, compared to 0.022/1000 prescriptions of buprenorphine (including buprenorphine-naloxone). The analysis generated a relative risk ratio of 6.23 (95 CI 4.79 to 8.10) of methadone in relation to buprenorphine. UK Borders Agency data were taken into consideration and revealed that only negligible amounts of methadone and buprenorphine were seized on entering UK territory between 2007 and 2012, suggesting domestic diversion.

CONCLUSIONS: Our analysis of the relative safety of buprenorphine and methadone for opioid substitution treatment reveals that buprenorphine is six times safer than methadone with regard to overdose risk among the general population. Clinicians should be aware of the increased risk of prescribing methadone, and tighter regulations are needed to prevent its diversion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

Key Words: buprenorphine; fatal overdose; methadone; relative risk
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