Question:
I read of a new Canadian study that says methadone is a better treatment for opioid use disorder than buprenorphine/naloxone. Is that true?
Answer:
The study you reference was a retrospective cohort examination of 30,891 individuals in British Columbia, Canada who initiated treatment for opioid use disorder between January 1, 2010 and March 17, 2020. During this period, by 2016, fentanyl had become the primary cause of overdose deaths in the province. The individuals studied were all 18 years or older, not incarcerated, pregnant, or receiving palliative cancer care at an institution. Two years after being provided either medication, the 61% who had chosen methadone were significantly more likely to continue taking the medication compared to the 39% who had chosen buprenorphine/naloxone. While the vast majority of each group discontinued their medication within two years, the discontinuation for the methadone group was 81.5% compared to 88.8% for the buprenorphine/naloxone group. Looking at just the 25,614 subsample who had received medication according to optimal dosing guidelines, the discontinuation rates were less, but those taking methadone were still less likely to discontinue their medication after two years, 30.7% compared to 42.1% for those taking buprenorphine/naloxone. Also, after two years since taking either medication, the all-cause mortality rate was higher for the methadone than the buprenorphine/naloxone group, 0.13% compared to 0.08% for the subgroup who received optimal dosing per guidelines. Among those deemed to be prevalent users, meaning not first-time users, the all-cause mortality was almost the same, 0.08% vs. 0.09%.
The researchers did not conclude that methadone is better treatment, that was a headline added by Physicians Weekly in a chart composed that summarized the study in “2 minute Medicine, Inc.”
The study cite is Nosyk, B., et al. (2024). Buprenorphine/Naloxone vs Methadone for the Treatment of Opioid Use Disorder. JAMA. doi.org/10.1001/jama.2024.16954.
It is important to note, the two groups in this study were not randomly selected. The differences in discontinuation and all-cause mortality between the two groups may be explained by factors other than the medications. The motivation and drug histories of the two groups may have differed which corresponded to their choice of medication. This who opted for buprenorphine primary motivation may have been to avoid withdrawal pain when they could not access opioids. Those opting for methadone may have been more medically fragile or high risk takers than those opting for buprenorphine which may have accounted for the differences in all-cause mortality. Also, perhaps most important, what is considered an “optimal” dose of buprenorphine/naloxone has changed in the past several years.
In October 2024, the American Medical Association (AMA) concluded that "new data highlight that the dose size currently recommended by the US Food and Drug Administration (FDA) and insurance caps on doses are outdated and harmful in the age of fentanyl overdoses." The AMA relied on data from a National Institute of Health (NIH) study. In this study, researchers reviewed insurance claims data from more than 35,000 people diagnosed with OUD who started on buprenorphine treatment between 2016 and 2021. They found that 12.5% had an emergency department (ED) or inpatient visit related to behavioral health within the study period. They analyzed whether a patient's buprenorphine dose was linked with the length of time between treatment start and an ED or inpatient visit. "Those taking daily doses of more than 24 mg of buprenorphine went 50% longer before having a subsequent emergency or inpatient healthcare visit related to behavioral health within the first year after receiving treatment, compared to those receiving > 8 to 16 mg a day.” The FDA’s recommended daily dose is 16 mg/d.
The study cite is Axeen S, Pacula RL, Merlin JS, Gordon AJ, Stein BD. Association of Daily Doses of Buprenorphine With Urgent Health Care Utilization. JAMA Netw Open. 2024;7(9):e2435478. doi:10.1001/jamanetworkopen.2024.35478.
In Canada, unlike the United States, methadone and buprenorphine/naloxone are available in both office-based settings and specialized drug treatment centers. That differs from the U.S., where methadone isn't available in office-based settings. The researchers said their Canadian study that found similar all-cause death rates supports U.S. advocates who argue that it is safe to allow methadone to be offered in office-setting in the United States too. The researchers also cautioned that “decisions about medication choice must be made in collaboration with patients.”