Buprenorphine/Naloxone vs Methadone for the Treatment of Opioid Use Disorder

Abstract

Importance: Previous studies on the comparative effectiveness between buprenorphine and methadone provided limited evidence on differences in treatment effects across key subgroups and were drawn from populations who use primarily heroin or prescription opioids, although fentanyl use is increasing across North America.

Objective: To assess the risk of treatment discontinuation and mortality among individuals receiving buprenorphine/naloxone vs methadone for the treatment of opioid use disorder.

Design, setting, and participants: Population-based retrospective cohort study using linked health administrative databases in British Columbia, Canada. The study included treatment recipients between January 1, 2010, and March 17, 2020, who were 18 years or older and not incarcerated, pregnant, or receiving palliative cancer care at initiation.

Exposures: Receipt of buprenorphine/naloxone or methadone among incident (first-time) users and prevalent new users (including first and subsequent treatment attempts).

Main outcomes and measures: Hazard ratios (HRs) with 95% compatibility (confidence) intervals were estimated for treatment discontinuation (lasting ≥5 days for methadone and ≥6 days for buprenorphine/naloxone) and all-cause mortality within 24 months using discrete-time survival models for comparisons of medications as assigned at initiation regardless of treatment adherence ("initiator") and received according to dosing guidelines (approximating per-protocol analysis).

Results: A total of 30 891 incident users (39% receiving buprenorphine/naloxone; 66% male; median age, 33 [25th-75th, 26-43] years) were included in the initiator analysis and 25 614 in the per-protocol analysis. Incident users of buprenorphine/naloxone had a higher risk of treatment discontinuation compared with methadone in initiator analyses (88.8% vs 81.5% discontinued at 24 months; adjusted HR, 1.58 [95% CI, 1.53-1.63]), with limited change in estimates when evaluated at optimal dose in per-protocol analysis (42.1% vs 30.7%; adjusted HR, 1.67 [95% CI, 1.58-1.76]). Per-protocol analyses of mortality while receiving treatment exhibited ambiguous results among incident users (0.08% vs 0.13% mortality at 24 months; adjusted HR, 0.57 [95% CI, 0.24-1.35]) and among prevalent users (0.08% vs 0.09%; adjusted HR, 0.97 [95% CI, 0.54-1.73]). Results were consistent after the introduction of fentanyl and across patient subgroups and sensitivity analyses.

Conclusions and relevance: Receipt of methadone was associated with a lower risk of treatment discontinuation compared with buprenorphine/naloxone. The risk of mortality while receiving treatment was similar for buprenorphine/naloxone and methadone, although the CI estimate for the hazard ratio was wide.

Figure 1.. Cohort Construction of Treatment for Opioid Use Disorder

OAT indicates opioid agonist treatment. ^aThe gap was defined as interruptions in prescribed OAT doses based on dispense date and day supply. Definitions of all terminology can be found in the Box. ^bIncludes incident users.

Figure 2.. Adjusted Cumulative Incidence Curves Among Incident Users in the Per-Protocol Analysis

Standardized for baseline covariates and weighed for time-varying confounders (sex, age, region, receipt of income assistance, unstable housing, incarcerated in the past year, cumulative years of prior opioid agonist treatment (OAT) exposure, year of OAT episode initiation, funding of OAT prescribers, OAT practice size, opioid dispensations for pain, drug-related acute care visits, Charlson Comorbidity Index, dispensation of psychiatric or sedative medication in the past months, other substance use disorder, alcohol use disorder, serious mental disorder, hepatitis C, chronic pain, treated tobacco use disorder, receipt of care in the past year for asthma or chronic obstructive pulmonary disease, attachment to the OAT prescriber, OAT take-home doses, urine drug test in the past week), and linear and quadratic product terms between an exposure and time. A, Median observation time, 1 (25th-75th, 1-3) week for buprenorphine/naloxone vs 3 (25th-75th, 1-3) weeks for methadone. B, Median observation time, 1 (25th-75th, 1-3) week for buprenorphine/naloxone vs 3 (25th-75th, 2-3) weeks for methadone.