# Slow-Release Oral Morphine vs Methadone for Opioid Use Disorder in the Fentanyl Era

## TL;DR

This study compares how often people stop using slow-release oral morphine versus methadone for opioid addiction and finds similar risks of death but higher dropout rates with morphine.

## Contribution

The study provides real-world evidence comparing SROM and methadone in the fentanyl era, focusing on discontinuation and mortality.

## Key findings

- SROM had a slightly higher 12-month discontinuation rate (99%) compared to methadone (98%).
- Mortality risk was similar between SROM and methadone, with only 2 deaths during treatment.
- Adherence was lower with SROM compared to methadone.

## Abstract

This comparative effectiveness study examines the discontinuation rates and mortality risk of slow-release oral morphine vs methadone for the treatment of opioid use disorder in Canadian adults during the fentanyl era.

What are the comparative discontinuation rates and mortality risks of slow-release oral morphine (SROM) vs methadone for the treatment of opioid use disorder (OUD) in the fentanyl era?

In this comparative effectiveness study that included 4059 person-trials in British Columbia, Canada, the rate of OUD treatment discontinuation at 12 months was slightly higher for people prescribed SROM vs methadone (99% vs 98%). The mortality risk was similar, and only 2 deaths occurred when people were receiving treatment.

In this study, SROM for OUD was associated with slightly higher treatment discontinuation risk than methadone but similar mortality risk, suggesting either medication may be appropriate alongside measures to support retention.

Slow-release oral morphine (SROM) is approved for the treatment of opioid use disorder (OUD) in several European countries and has been used off label in Canada since 2017. However, the evidence base to support its use is limited and predates the fentanyl era.

To compare the discontinuation rates and mortality risks of SROM vs methadone for the treatment of OUD.

This comparative effectiveness study with a target trial emulation approach used data from observational linked health administrative databases in the Vancouver Coastal Health Authority (VCHA) region in British Columbia, Canada, between July 1, 2017, and June 30, 2024. Participants were adults aged 19 to 65 years with OUD.

New prescription of SROM or methadone for OUD (ie, no dispensation of medications for OUD in the 7 days prior) within VCHA clinical services.

Estimated 12-month risk of treatment discontinuation (≥7 days without medication dispensation) and all-cause mortality, as well as treatment adherence (proportion of days covered [PDC]) over 12 months of follow-up. Both intention-to-treat (ITT) and per-protocol (PP; restricted to episodes where SROM or methadone was dispensed within 4 days of the prescription) analyses were conducted.

A total of 3254 unique individuals (median age, 37 [IQR, 30-46] years; 2088 [64.2%] male) contributed to 4059 person-trials (2737 [67.4%] methadone, 1322 [32.6%] SROM) for the ITT analysis, and 1992 unique individuals contributed to 2276 person-trials (1653 [72.6%] methadone, 623 [27.4%] SROM) for the PP analysis. In ITT analyses, the standardized cumulative incidence of discontinuation at 12 months was 99.3% (95% CI, 99.0%-99.5%) and 97.9% (95% CI, 97.5%-98.2%) in the SROM and methadone arms, respectively (adjusted risk difference [ARD], 1.4 percentage points [pp]; 95% CI, 1.0-1.9 pp). PDC was also lower in the SROM group (adjusted risk ratio, 0.89; 95% CI, 0.87-0.91), while mortality risk was similar between arms (ARD, 1.1 pp; 95% CI, −1.3 to 4.1 pp). Of 121 total deaths, only 2 (1.7%) occurred when people were receiving MOUD. PP analyses yielded similar results.

In this comparative effectiveness study of adults with OUD in a Canadian setting, treatment discontinuation was common. Compared with methadone, SROM was associated with a slightly higher risk of treatment discontinuation and lower adherence but similar mortality risk. The findings suggest either medication may be appropriate if measures are in place to support retention.