Abundant evidence has established OAT’s effectiveness in sustaining treatment retention, reducing unregulated opioid use, and minimizing risk of morbidity and mortality.111-116 The choice of agonist treatment depends on several patient-specific factors including initial presentation, history and patterns of substance use, comorbidities (e.g., liver disease, prolonged QTc interval), drug–drug interactions, treatment preference and goals, life style requirements and restrictions (e.g., remote location of home or employment), and response to treatment. Regardless of the type of treatment administered, opioid agonist treatment should incorporate provider-led counselling, long-term continuing care (e.g., regular assessment, follow-up), provision of comprehensive preventive and primary care, and referrals to psychosocial treatment interventions, psychosocial supports, and specialist care as required, to optimize physical and mental wellness and support reaching patient-defined goals.

Much of the evidence supporting available opioid agonist medications pre-dates the widespread adulteration of the unregulated drug supply with fentanyl and other highly potent psychoactive substances. However, the limited available evidence demonstrates that OAT has significant efficacy in reducing the risk of overdose mortality among people with OUD who use fentanyl.117-119 For example, a 2020 observational study (n=55,347) compared the risk of mortality between participants on OAT and those off OAT in a cohort of British Columbians who received methadone or buprenorphine between 1996 and 2018.117 The relative risk of death among people off OAT was 2.1 times higher than participants on OAT before the introduction of fentanyl, increasing to 3.4 times higher than those on OAT in 2016, when a public health emergency was declared due to the infiltration of fentanyl in the unregulated drug supply. The mortality rate of people on OAT remained stable between 2010 and 2018, suggesting that being on OAT offered substantial protection from overdose during the fentanyl crisis.117 

The impact of fentanyl use on OAT initiation and engagement was investigated in a 2022 secondary analysis of a Canadian clinical trial (n=272) conducted between 2017 and 2022. While unadjusted analysis suggested that baseline fentanyl exposure was associated with lower likelihood of OAT initiation [odds ratio (OR)=0.18, 95% CI: 0.08–0.36] and shorter periods of engagement in OAT [20 vs 168 days, hazard ratio (HR)=3.61, 95% CI: 2.52–5.17], adjusted models showed no statistically significant differences between participants with and without fentanyl exposure at baseline.119 The authors concluded that both buprenorphine/naloxone and methadone are appropriate treatment options for people with opioid use disorder regardless of fentanyl exposure.119

Clinical experience indicates that some individuals with high opioid tolerance due to fentanyl use may require modified dosing and titration protocols, in addition to significantly higher OAT doses than were common prior to fentanyl predominating the unregulated opioid supply. In the absence of substantial evidence characterising and evaluating these modified practices intended to meet the needs of patients who use fentanyl, the dosing and titration guidance provided in this document was developed through expert consensus and in reference to accumulating clinical experience and guidance emerging in other jurisdictions—such as the Ontario-based Methadone Treatment for People Who Use Fentanyl: Recommendations published by Mentoring, Education, and Clinical Tools for Addiction—Partners in Health Integration (META-PHI)— as well as emerging research.120 See Appendix 3 for guidance on dosing and titration.