Objective To compare the risk of mortality among people with opioid use disorder on and off opioid agonist treatment (OAT) in a setting with a high prevalence of illicitly manufactured fentanyl and other potent synthetic opioids in the illicit drug supply. Design Population based retrospective cohort study. Setting Individual level linkage of five health administrative datasets capturing drug dispensations, hospital admissions, physician billing records, ambulatory care reports, and deaths in British Columbia, Canada. Participants 55 347 people with opioid use disorder who received OAT between 1 January 1996 and 30 September 2018. Main outcome measures All cause and cause specific crude mortality rates (per 1000 person years) to determine absolute risk of mortality and all cause age and sex standardised mortality ratios to determine relative risk of mortality compared with the general population. Mortality risk was calculated according to treatment status (on OAT, off OAT), time since starting and stopping treatment (1, 2, 3-4, 5-12, >12 weeks), and medication type (methadone, buprenorphine/naloxone). Adjusted risk ratios compared the relative risk of mortality on and off OAT over time as fentanyl became more prevalent in the illicit drug supply. Results 7030 (12.7%) of 55 347 OAT recipients died during follow-up. The all cause standardised mortality ratio was substantially lower on OAT (4.6, 95% confidence interval 4.4 to 4.8) than off OAT (9.7, 9.5 to 10.0). In a period of increasing prevalence of fentanyl, the relative risk of mortality off OAT was 2.1 (95% confidence interval 1.8 to 2.4) times higher than on OAT before the introduction of fentanyl, increasing to 3.4 (2.8 to 4.3) at the end of the study period (65% increase in relative risk). Conclusions Retention on OAT is associated with substantial reductions in the risk of mortality for people with opioid use disorder. The protective effect of OAT on mortality increased as fentanyl and other synthetic opioids became common in the illicit drug supply, whereas the risk of mortality remained high off OAT. As fentanyl becomes more widespread globally, these findings highlight the importance of interventions that improve retention on opioid agonist treatment and prevent recipients from stopping treatment.

Formatted for AddictionThe cascade of care for opioid use disorder: a retrospective study in

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IntroductionOpioid agonist treatment (OAT) is a safe and effective treatment for opioid use disorder (OUD). However, people commonly stop and start OAT and their risk of death is high immediately after stopping. The prevalence of illicitly manufactured fentanyl and other highly potent synthetic opioids have increased in the illicit drug supply globally. Yet, there is limited evidence examining the relationship between OAT and mortality when these contaminants are widely available in the illicit drug supply. Objectives and ApproachWe aimed to compare the risk of mortality on and off OAT in a setting with a high prevalence of illicitly manufactured fentanyl and other potent synthetic opioids in the illicit drug supply. We linked five health administrative datasets in British Columbia, Canada, creating a cohort of 55,347 people with OUD who received OAT during a 23-year period (1996 to 2018). We compared the risk of mortality on and off treatment over time, and according to time since starting or stopping treatment and by medication type. Results7,030 of 55,347 (12.7%) OAT recipients died during follow-up. All-cause SMR was substantially lower on OAT (4.6 [4.4 to 4.8]) compared to off OAT (9.7 [9.5 to 10.0]). In a period of increasing prevalence of fentanyl, the relative risk of mortality off OAT was 2.1 [1.8 to 2.4] times higher than on OAT prior to the introduction of fentanyl, and increased to 3.4 [2.8 to 4.3] at the end of the study period (65% increase in relative risk). Conclusion / ImplicationsThe protective effect of OAT on mortality increased as fentanyl and other synthetic opioids became common in the illicit drug supply, while the risk of mortality remained high off OAT. As fentanyl becomes more widespread globally, these findings highlight the importance of interventions that improve retention on opioid agonist treatment and prevent recipients from stopping treatment.