Canada’s Methadone Prescribing Changes With Drug Supply

Canada’s new methadone-prescribing guidance has influenced clinicians’ practice, new data suggest.

The publication of the guidance was associated with higher starting doses of methadone and a decrease in monotherapy. The provision of rapid dose titration, however, has remained limited.

“Though we noticed that there was an increasing trend toward higher doses in the second week of treatment, this was primarily driven by these patients being prescribed a higher dose,” study author Ria Garg, PharmD, PhD student at the University of Toronto’s Leslie Dan Faculty of Pharmacy, Toronto, told Medscape Medical News. “But most patients were not receiving an early dose titration within 4-6 days as recommended. We felt that this was a missed opportunity for reaching therapeutic effects.” 

The study was published on August 15 in JAMA Network Open. 

Decline in Monotherapy

The illegal opioid drug supply in Canada is thriving. Health Canada reported that 74% of opioid-related deaths in 2024 involved fentanyl, and 80% of these deaths occurred in British Columbia, Alberta, and Ontario. 

Methadone and buprenorphine are first-line opioid agonist treatment (OAT) options for clinicians treating these patients. Methadone appears to be especially effective for reducing treatment dropout and subsequent overdose, and patients on long-term methadone have also been shown to develop cross-tolerance to fentanyl-related respiratory depression. The current findings suggest, however, that methadone initiation in patients may be lagging recent recommendations that were developed to optimize therapeutic outcomes.

“We wanted to look at how the META-PHI [Mentoring, Education, And Clinical Tools for Addiction-Partners in Health Integration] 2020 guidance for prescribing methadone was impacting physician behavior and producing meaningful changes,” said Garg. 

Garg and her team examined methadone initiations captured in Ontario between July 1, 2013, and July 31, 2023, to determine the extent to which prescribing practices had been adapted to the META-PHI guidance and to an unpredictable, fentanyl-dominated, unregulated drug supply. A 30-day lookback period was used to define recent use of shorter-acting OAT formulations and immediate-release hydromorphone. A 210-day lookback period was used for longer-acting formulations. Participants receiving palliative care or with cancer diagnosis, as well as those aged < 18 years or > 105 years were excluded. 

The researchers identified 73,633 incident methadone starts in 35,309 participants, most of whom were aged 25-44 years and were men. Most prescribers were either family physicians or high-volume OAT prescribers. 

The introduction of the META-PHI prescribing guidance in September 2020 was associated with a sustained decline in methadone monotherapy initiation (ramp estimate, -0.27/100,000, P = .01) and a concurrent increase in combination therapy initiation. The researchers also observed a shift toward higher methadone doses (30 mg to < 40 mg) on index and within the first 2 treatment weeks (ramp estimate, 1.59%). However, initiations without any dose titration over the first 2 weeks increased in prevalence from 38.5% to 45.7%. Dose titration within 6 days was less prevalent among combination therapy initiations (29.2%). 

“The goal for clinicians is to get patients to show up for treatment and engage. So, if you are not getting them over 60 mg, it is a missed opportunity to keep them coming back,” added Leonora Regenstreif, MD, assistant clinical professor (adjunct) of family medicine at McMaster University in Hamilton, Ontario, and coauthor of the META-PHI recommendations, 

Qualitative Data Absent

For patients with opioid tolerance, especially those who report fentanyl use, the goals of treatment are to improve retention rates and abstinence and prevent overdose, Regenstreif told Medscape Medical News. Regenstreif was not involved in the study. 

“The gist of the META-PHI guidance was the evidence that 40 mg starts could be done safely and without harm in people with very high opioid tolerance who also could not remember if they’d recently been on methadone,” said Regenstreif. Concomitant administration of slow-release oral morphine 200 mg was recommended to address withdrawal or cravings in patients cycling through methadone starts, with known tolerance, or at high risk for fentanyl overdose.

The guidance also underscored the need for rapid titration, which means increasing the starting methadone dose first by 10-15 mg every 3-5 days. Once a 75-mg to 80-mg dose has been reached, the dose can be increased by 10 mg every 5-7 days to a maximum 120 mg to ensure that patients do not return to fentanyl.

Though administrative data are adequate for examining trends, the team was unable to capture opioid use patterns in the current study.

“We also don’t know physician comfort level (for example, if the prescribers were not comfortable increasing doses during the second week because patients were not showing up and missed multiple days),” said Regenstreif. “Administrative databases don’t really dive deeply enough and lack a qualitative component.” Likewise, physicians might have been extra cautious when treating high-risk individuals. The guidance notes that physicians should use their judgement and consider individual patient circumstances and patterns of tolerance, especially if they have missed five consecutive doses.

The goal is to optimize treatment retention, which is always greater with flexible, individualized dosing. Physicians should also be on the lookout for the updated META-PHI guidance, which is slated for release within a few months, said Regenstreif. 

The study was funded by ICES, the Ontario Ministry of Health and the Canadian Institutes, of Health Research. Garg reported having no relevant financial relationships. Regenstreif reported receiving honoraria from Indivior Canada.

Liz Scherer is a health and medical journalist. She frequently covers Canadian and EU health news on behalf of Medscape Medical News.