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Prescription of benzodiazepines, z-drugs, and gabapentinoids and mortality risk in people receiving opioid agonist treatment: Observational study based on the UK Clinical Practice Research Datalink and Office for National Statistics death records

Author

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  • John Macleod
  • Colin Steer
  • Kate Tilling
  • Rosie Cornish
  • John Marsden
  • Tim Millar
  • John Strang
  • Matthew Hickman

Abstract

Background: Patients with opioid dependency prescribed opioid agonist treatment (OAT) may also be prescribed sedative drugs. This may increase mortality risk but may also increase treatment duration, with overall benefit. We hypothesised that prescription of benzodiazepines in patients receiving OAT would increase risk of mortality overall, irrespective of any increased treatment duration. Methods and findings: Data on 12,118 patients aged 15–64 years prescribed OAT between 1998 and 2014 were extracted from the Clinical Practice Research Datalink. Data from the Office for National Statistics on whether patients had died and, if so, their cause of death were available for 7,016 of these patients. We identified episodes of prescription of benzodiazepines, z-drugs, and gabapentinoids and used linear regression and Cox proportional hazards models to assess the associations of co-prescription (prescribed during OAT and up to 12 months post-treatment) and concurrent prescription (prescribed during OAT) with treatment duration and mortality. We examined all-cause mortality (ACM), drug-related poisoning (DRP) mortality, and mortality not attributable to DRP (non-DRP). Models included potential confounding factors. In 36,126 person-years of follow-up there were 657 deaths and 29,540 OAT episodes, of which 42% involved benzodiazepine co-prescription and 29% concurrent prescription (for z-drugs these respective proportions were 20% and 11%, and for gabapentinoids 8% and 5%). Concurrent prescription of benzodiazepines was associated with increased duration of methadone treatment (adjusted mean duration of treatment episode 466 days [95% CI 450 to 483] compared to 286 days [95% CI 275 to 297]). Benzodiazepine co-prescription was associated with increased risk of DRP (adjusted HR 2.96 [95% CI 1.97 to 4.43], p

Suggested Citation

  • John Macleod & Colin Steer & Kate Tilling & Rosie Cornish & John Marsden & Tim Millar & John Strang & Matthew Hickman, 2019. "Prescription of benzodiazepines, z-drugs, and gabapentinoids and mortality risk in people receiving opioid agonist treatment: Observational study based on the UK Clinical Practice Research Datalink an," PLOS Medicine, Public Library of Science, vol. 16(11), pages 1-16, November.
    • Handle: RePEc:plo:pmed00:1002965
    DOI: 10.1371/journal.pmed.1002965
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    Cited by:

    1. Aina Perelló-Bratescu & Christian Dürsteler & Maria Asunción Álvarez-Carrera & Laura Granés & Belchin Kostov & Antoni Sisó-Almirall, 2022. "Risk Prescriptions of Strong Opioids in the Treatment of Chronic Non-Cancer Pain by Primary Care Physicians in Catalonia: Opicat Padris Project," IJERPH, MDPI, vol. 19(3), pages 1-10, January.

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