Prescribing Characteristics Associated With Opioid Overdose Following Buprenorphine Taper

Abstract

ImportanceRetention in buprenorphine therapy is associated with a lower risk of opioid overdose. Nevertheless, many patients discontinue treatment, and there is limited evidence to guide buprenorphine tapering.ObjectiveTo understand what prescribing characteristics are associated with opioid overdose following buprenorphine taper.Design, Setting, and ParticipantsThis is a population-based, retrospective, cohort study of adults who were maintained on buprenorphine for at least 60 days and underwent a buprenorphine taper. The study was conducted in the Canadian province of Ontario, using linked administrative health data. New buprenorphine treatment episodes were accrued between January 1, 2013, and January 1, 2019, and the maximum follow-up was April 30, 2020. Data analysis was performed from December 2020 to August 2022.ExposuresThe primary exposure of interest was time to taper initiation (≤1 year vs >1 year). Secondary exposures included mean rate of taper, percentage days during which the dose was decreasing, and taper duration.Main Outcomes and MeasuresThe primary outcome measure was time to fatal or nonfatal opioid overdose within 18 months following treatment discontinuation.ResultsAmong 5774 individuals, the median (IQR) age at index date was 34 (28-44) years, and 3462 individuals (60.0%) were male. Time to taper initiation longer than 1 year vs 1 year or less (6.73 vs 10.35 overdoses per 100 person-years; adjusted hazard ratio [aHR], 0.69; 95% CI, 0.48-0.997), a lower mean rate of taper (≤2 mg per month, 6.95 overdoses per 100 person-years; >2 to ≤4 mg per month, 11.48 overdoses per 100 person-years; >4 mg per month, 17.27 overdoses per 100 person-years; ≤2 mg per month vs >4 mg per month, aHR, 0.65; 95% CI, 0.46-0.91; >2 to ≤4 mg per month vs >4 mg per month, aHR, 0.69; 95% CI, 0.51-0.93), and dose decreases in 1.75% or less of days vs more than 3.50% of days during the taper period (5.87 vs 13.87 overdoses per 100 person-years; aHR, 0.64; 95% CI, 0.43-0.93) were associated with reduced risk of opioid overdose; however, taper duration was not.Conclusions and RelevanceIn this retrospective cohort study, buprenorphine tapers undertaken after at least 1 year of therapy, a slower rate of taper, and a lower percentage of days during which the dose was decreasing were associated with a significantly lower risk of opioid overdose, regardless of taper duration. These findings underscore the importance of a carefully planned taper and could contribute to reduction in opioid-related overdose death.

Opioid Agonist Treatment Retention Among People Initiating Methadone and Buprenorphine Across Diverse Demographic and Geographic Subgroups in Ontario: A Population-based Retrospective Cohort Study

“…We selected a 14-day interval because an interruption in treatment of this length would warrant reinitiating treatment, and has been used previously. 20,21 Among those who discontinued OAT, we defined the date of discontinuation as the dispensing date of the final prescription plus the day supply. We followed each person for up to 3 years, until the first of OAT discontinuation, switch between methadone and buprenorphine/naloxone, death, or December 31, 2019, whichever occurred first.…”

“…Our primary outcome was time to treatment discontinuation, defined as missing a minimum of 14 consecutive days of the OAT initially prescribed, regardless of whether dose was tapered. We selected a 14-day interval because an interruption in treatment of this length would warrant reinitiating treatment, and has been used previously 20,21 . Among those who discontinued OAT, we defined the date of discontinuation as the dispensing date of the final prescription plus the day supply.…”

What is the ideal time to begin tapering opioid agonist treatment? A protocol for a retrospective population-based comparative effectiveness study in British Columbia, Canada

“…To this end, three clinical trials reported higher relapse rates after completing methadone taper, ranging from 53.1% to 66.7% of individuals relapsed by the first month and 61.1% to 89.2% by the sixth month after taper completion 1 16–18. Furthermore, the ideal duration of stability before a taper is initiated may be related to clients’ clinical course, severity, adherence to OAT treatment and other social factors such as family support and financial status, housing status and neighbourhood environment 1 4 19–23. A retrospective cohort study with 8996 clients who discontinued buprenorphine treatment found that individuals who were retained in treatment for 15–18 months had a lower probability of emergency department visits, hospitalisations and filling opioid prescriptions in the 6 months following discontinuation than individuals retained for 6–9 months 24.…”

“…Studies from BC, Canada, and Guangdong, China, both demonstrated that more gradual and staggered dose decreases increased the likelihood of taper completion 4 26. A retrospective cohort study of 5774 individuals undergoing a buprenorphine taper reported that regardless of the tapering strategy, however, the time to taper initiation demonstrated an independent effect on the likelihood of successful taper completion,20 in contrast to the prior study from BC involving methadone 4. The independent effect of when the OAT taper is initiated or the possible effects of OAT medication type in the treatment course thus remains unclear.…”

Non‐scheduled short‐acting opioid to taper off opioids?

“…These patients could benefit initially from a gradual opioid tapering using quick onset and short‐acting opioids without known addiction properties. Whereas buprenorphine taper is clinically used, it takes very long time to taper down due to it long half‐life and it is associated with post‐taper overdose death, and buprenorphine itself is addictive 9 . In the future drug development for addiction therapy, short‐acting regimen for an easy taper down or taper off opioids should be explored.…”