Methadone much more effective than buprenorphine/naloxone for treatment retention, with no difference in mortality risk, study finds

The new research, published this week in the Journal of the American Medical Association, evaluated the risk of treatment discontinuation and mortality in people prescribed opioid agonist treatment (OAT) over a 10-year period.

"Reducing the risk of treatment discontinuation saves lives. With thousands of lives lost since the introduction of fentanyl into B.C.'s unregulated drug supply, it is important that we continue to evaluate the best available treatment options," said Dr. Bohdan Nosyk, scientist at the Centre for Advancing Health Outcomes and a professor in the Faculty of Health Sciences at Simon Fraser University. "Comparative studies like this using high-quality health administrative data are one of the best sources of evidence we have to evaluate how our treatment options are performing as the toxic drug supply continues to evolve."

The study, Buprenorphine/naloxone versus methadone for the treatment of opioid use disorder, was a collaboration between scientists and public health professionals from the Centre for Advancing Health Outcomes, Simon Fraser University, BC Centre on Substance Use, University of British Columbia (UBC), and McGill University in Canada, and universities and institutions in the United Kingdom, Austria, and across the United States.

This study included everyone in B.C. who received either methadone or buprenorphine/naloxone for opioid use disorders from Jan 1, 2010 to Mar 17, 2020 (30,891 people) and compared the impact of these medications on retention and all-cause mortality. Fentanyl was first detected in the drug supply in 2012 and became the primary driver of overdose mortality in 2016. The study period ended the day before BC declared a public health emergency for COVID-19. Just over 61 per cent of people in the cohort were prescribed methadone.

The study found that the risk of treatment discontinuation was lower among recipients of methadone compared with buprenorphine/naloxone. The risk of mortality was low during treatment and did not differ meaningfully between the two medications (0.13% vs. 0.08%). Importantly, these findings were consistent after the introduction of fentanyl and across patient subgroups, including youth (<24 years), people with severe mental disorders, and people with concurrent chronic pain.

"The benefits of these medications are only realized while people are using them. However, retention in OAT has steadily declined over the past 13 years," said Dr. Paxton Bach, Clinical Assistant Professor in the Department of Medicine at UBC, Co-Medical Director for the BC Centre on Substance Use, and a co-author on the study. "Continuous evaluation and refinement of clinical guidance based on the strongest available evidence is vital in order to provide the best possible support to people with opioid use disorder in BC and around the world."

Earlier research shows that mortality risk for people on OAT more than doubles after treatment discontinuation versus while on treatment.

The researchers noted that while this evidence suggests that methadone remains the treatment option with the strong evidence of effectiveness, decisions about medication choice must be made in collaboration with patients. Developing novel therapeutic regimens, like co-prescription of hydromorphone, is also an urgent priority. Additionally, there needs to be consideration the existing barriers to treatment retention, like urine drug screening and daily witnessed doses, and incorporation of strategies to improve retention, like engagement of peer support workers.

Funding for this study was provided by the Health Canada Substance Use and Addictions Program and the National Institute on Drug Abuse of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.

Background

• B.C. has seen rapid uptake of fentanyl use among people with opioid use disorder since its first detection in provincial coroner's records in 2012. Fentanyl and its analogues have been detected in over 82% of all drug overdose deaths in BC each year since 2017.
• According to the latest release from the BC Coroners Service, about six people per day die from unregulated drugs.
• Both buprenorphine/naloxone and methadone are available in specialized drug treatment centres and in office-based settings in B.C.
• This study was done using anonymized administrative health data. People who accessed OAT were not identified by name and the outcomes of OAT were assessed based on their interactions with the health care system.