Treating opioid use disorder has grown far more difficult in the fentanyl era. A major study in JAMA Network Open (March 2026) compares two medications for opioid use disorder and examines how well each keeps people on treatment. The findings are sobering, and they matter for anyone trying to understand what works today.

What the Research Looked At

The study was conducted in British Columbia, Canada. Researchers compared slow-release oral morphine (SROM) and methadone as treatments for OUD. Both are opioid agonist therapies. They stabilise the brain’s opioid receptors to reduce cravings and withdrawal without producing the intense high linked to street drugs.

SROM has been available in several European countries for some time. Canada approved its off-label use in 2017. However, earlier evidence came from smaller studies. None of them included people using illicitly manufactured fentanyl. This new study used real-world data from over 4,000 treatment episodes in the Vancouver Coastal Health Authority region between 2017 and 2024.

Key Findings on Opioid Use Disorder Treatment

The results show just how hard it is for people to stay on opioid use disorder treatment.

Over 12 months, discontinuation rates were extremely high for both medications. Among those on methadone, roughly 98% had a treatment gap of 7 or more days within a year. For those on SROM, that figure rose to approximately 99%. Staying on either medication for a full year was the exception, not the rule.

Among people who actually started their prescribed medication, the gap between treatments widened slightly. Methadone had a 12-month discontinuation rate of around 95.7%. SROM reached 98.5%. Adherence was also lower for SROM. People on SROM took their medication on about 37% of days during follow-up. Those on methadone managed around 43%.

One finding stands out: of 121 total deaths recorded, only 2 occurred while people were receiving treatment. That is a striking number. It shows how protective staying on medication can be and how dangerous treatment gaps are.

Mortality Risk Was Similar for Both Medications

No statistically significant difference in mortality appeared between the two groups. Adjusted 12-month mortality sat at around 8.2% for SROM and 7.0% for methadone. That gap was not large enough to rule out chance.

This result matters. Methadone may be somewhat easier to stay on. But SROM does not carry a worse survival outcome. For a patient who cannot or will not take methadone, SROM remains a clinically reasonable option when the right support is in place.

Why Are Opioid Use Disorder Treatment Discontinuation Rates So High?

Several factors help explain the low retention rates in this study. They are notably worse than older research figures.

Fentanyl is far more potent than heroin. People who use it typically need higher medication doses to stabilise. The drug supply during the study period also frequently contained other substances such as benzodiazepines and xylazine. That made clinical management considerably more complex.

SROM presents an additional challenge. It is newer. Many prescribers in North America have limited experience with it. Clinicians may struggle to titrate doses and support patients through the difficult early stages of treatment. The study found that prescriber habits played a meaningful role in which medication patients received. This hints that clinical confidence and familiarity shape how well people are supported on a given drug.

The COVID-19 pandemic also disrupted clinic access and in-person support throughout the study period.

What This Means for Opioid Use Disorder Treatment Going Forward

The key message here is not simply that one drug beats the other. The bigger concern is that treatment discontinuation is overwhelmingly common for both medications. That represents a serious public health problem.

Nearly all deaths in the study occurred during treatment gaps. Improving retention on any form of medication for opioid use disorder must therefore be a priority. The researchers note that either methadone or SROM may suit different patients depending on their circumstances. Active steps to support continuity of care are essential either way.

Access to treatment also remains alarmingly limited. In 2022, only around 25% of the estimated 6 million Americans with OUD received any medication-based treatment. Figures in British Columbia were similarly low. A treatment that a patient will actually engage with is far better than one they will not, regardless of which performs better on paper.

A Note on Context

This study took place in a specific urban Canadian setting. Healthcare, including medication for OUD, is publicly funded there. Results may not translate directly to countries with different healthcare systems or to rural populations facing different access challenges. Even so, the scale of the discontinuation problem is likely to resonate well beyond Vancouver.

The real question is not only which medication works best in theory. It is how we build clinical systems and relationships that help people stay on opioid use disorder treatment long enough to benefit.

Source: jamanetwork