Login
Subscribe
Oral daily doses of the opioid methadone (METHADOSE and generics) and daily dosing with the opioid combination buprenorphine-naloxone (SUBOXONE, ZUBSOLV and generics) are similarly effective to treat opioid use disorder (OUD) according to a large observational study of patients in British Columbia, Canada.[1] The use of methadone, however, was associated with a lower risk of discontinuing treatment.
The findings are important because both drugs are now widely used to treat OUD, although in...
Oral daily doses of the opioid methadone (METHADOSE and generics) and daily dosing with the opioid combination buprenorphine-naloxone (SUBOXONE, ZUBSOLV and generics) are similarly effective to treat opioid use disorder (OUD) according to a large observational study of patients in British Columbia, Canada.[1] The use of methadone, however, was associated with a lower risk of discontinuing treatment.
The findings are important because both drugs are now widely used to treat OUD, although in the United States methadone can only be dispensed in special clinics that a person must visit daily. Buprenorphine-naloxone can be prescribed in common outpatient clinics, and patients can fill multiday prescriptions at their preferred pharmacy.
Opioid use disorder
In 2023 an estimated 2% of people (approximately 5.7 million people) in the United States who were 12 years of age or older had an OUD.[2] The diagnosis of an OUD requires at least three of the following six signs: 1) strong desire to use, 2) difficulty controlling use, 3) withdrawal symptoms upon ceasing use, 4) tolerance to the effects (the need for ever-increasing doses), 5) neglecting pleasures or interests because of the desire to use, and 6) persistent use despite clearly harmful consequences.[3]
Opioid use disorder leads to substantial day-to-day dysfunction. Overdose of prescription or illegal opioids has been involved in the deaths of over 727,000 people in the United States since 1999, including an estimated 82,000 deaths in 2022.[4]
The Centers for Disease Control and Prevention has identified three waves of opioid overdose deaths: 1) an increase in deaths related to prescription opioids (for example, codeine [generics only], hydrocodone [HYSINGLA and generics] and oxycodone [OXYCONTIN, ROXICODONE, ROXYBOND, XTAMPZA ER and generics]) that began in 1990; 2) an increase in deaths related to heroin, a semi-synthetic, illegal drug, that began in 2010; and 3) an increase in deaths related to synthetic opioids, especially illegal fentanyl and its analogues, that began in 2013.[5]
Although methadone is also a synthetic opioid, recent data show that its contribution to overdose deaths is declining, whereas deaths involving fentanyl continue to increase.[6] Fentanyl, which is approximately 50-100 times more potent than morphine and 25 times more potent than heroin, has become a dominant and often hidden component (in laced heroin or fake tablets) of the illicit opioid trade.[7]
Treating OUD is very challenging. Treatment that includes either daily methadone or buprenorphine is a long-established method to support recovery.[8] The new study is important because previous studies directly comparing methadone and buprenorphine are few. Prior studies were focused on heroin users, not users of other synthetic opioids.[9]
The Canadian study[10]
The Canadian study was published in JAMA in 2024.[11] To compare the effectiveness of buprenorphine-naloxone to methadone, Canadian researchers linked the administrative health records for 30,891 treated patients in British Columbia who initiated the use of these drugs between January 2010 and March 2020. Only adults (median age 33 years) were included; people who were incarcerated, pregnant or receiving palliative cancer care were excluded. Approximately 66% of the patients were men, 12% lived in a rural region, 48% had a history of OUD medication treatment, and 43% were past-year recipients of income assistance.
The main outcomes assessed were treatment discontinuation and all-cause mortality over 24 months. Treatment was flagged as discontinuous (interrupted) when a patient missed at least five or six consecutive days of their methadone or buprenorphine-naloxone doses, respectively.
Treatment discontinuity was high with the use of both medications and significantly higher for those on buprenorphine-naloxone (89%) than for those on methadone (82%). Among a subset of 25,614 patients (83% of the total) who were treated “per protocol” (sustained treatment including at least one guideline-recommended dose and without medication switching), the discontinuity rates were markedly lower and slightly more disparate between buprenorphine-naloxone (42%) and methadone (31%).
The risk of death while receiving treatment was low and similar between medications: 0.08% for buprenorphine-naloxone (fewer than 10 deaths) and 0.13% for methadone (20 deaths). This difference in mortality, measured over 24 months, was small.
The British Columbia, Canada, study was an observational study, not a clinical trial in which participants were randomized to either buprenorphine-naloxone or methadone treatment. To minimize the risk of bias, the researchers used study design and statistical methods to balance the comparison groups and to account for other factors that may have influenced the findings, including gender, age, income and housing status, past incarceration, past use of opioids or other substance use disorder treatments, and the presence of other illnesses (including serious mental health disorders and asthma).
Support for expanding methadone access
Also in 2024, JAMA published an opinion article entitled “Methadone’s Moment” by two physicians and one patient advocate who were not involved in the Canadian study.[12] The authors argued that methadone is too often neglected in the United States as a treatment for OUD, “hindered by decades-old policies that limit its delivery,” including daily observed-in-the-clinic dosing; few and isolated opioid treatment clinics that are concentrated in or near cities and too separated from other medical locations; and insufficient access at critical transition points such as hospitals, jails and nursing homes.
The article advocated for policies that allow hospitals to dispense multiday, urgent supplies of methadone, add methadone treatment for OUD as a service covered under the Americans with Disabilities Act, and expand flexible (including telehealth) prescribing practices for methadone and buprenorphine-naloxone that were implemented during the COVID-19 pandemic.
What You Can Do
Both buprenorphine-naloxone and methadone are powerful opioid receptor agonists (promotors) with many adverse effects and should be used only by knowledgeable clinicians to treat OUD.[13],[14] These adverse effects include overdose and respiratory depression possibly resulting in death, sedation, constipation, liver toxicity, sexual dysfunction, and fetal and adult withdrawal.
The new study underscores the role of methadone as a treatment for OUD. If you require treatment for OUD, consult with a licensed clinician and know that at present in the United States methadone is only available through daily contact with a certified opioid treatment program. If you seek OUD treatment, use social services (including psychotherapy[15]) to support your recovery. Relapses and discontinuation of treatment are common.
References
[1] Nosyk B, Min JE, Homayra F, et al. Buprenorphine/naloxone vs methadone for the treatment of opioid use disorder. JAMA. 2024;332(21):1822-1831.
[2] Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2023 National Survey on Drug Use and Health. July 2024. (HHS Publication No. PEP24-07-021, NSDUH Series H-59). https://www.samhsa.gov/data/report/2023-nsduh-annual-national-report. Accessed February 4, 2025.
[3] Nielsen S, Tse WC, Larance B. Opioid agonist treatment for people who are dependent on pharmaceutical opioids. Cochrane Database of Syst Rev. 2022;9(9):CD011117.
[4] Centers for Disease Control and Prevention. Overdose prevention. Understanding the opioid overdose epidemic. November 1, 2024. https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdose-epidemic.html. Accessed February 4, 2025.
[5] Ibid.
[6] Spencer MR, Garnett MF, Minino AM. Drug overdose deaths in the United States, 2002-2022. National Center for Health Statistics data brief. March 2024. https://www.cdc.gov/nchs/data/databriefs/db491.pdf. Accessed February 4, 2025.
[7] Pardo B, Taylor J, Caulkins J, et al. The dawn of a new synthetic opioid era: the need for innovative interventions. Addiction. 2021;116(6):1304-1312.
[8] Facher L. RFK Jr. endorses medications for opioid addiction at confirmation hearing, but misleads on 12-step programs. STAT. January 30, 2025.
[9] Nielsen S, Tse WC, Larance B. Opioid agonist treatment for people who are dependent on pharmaceutical opioids. Cochrane Database of Systematic Reviews. 2022;9(9):CD011117.
[10] Nosyk B, Min JE, Homayra F, et al. Buprenorphine-naloxone vs methadone for the treatment of opioid use disorder. JAMA. 2024;332(21):1822-1831.
[11] Incze MA, Simon C, Suen LW. Methadone's moment. JAMA. 2024;332(23):1969-1970.
[12] Incze MA, Simon C, Suen LW. Methadone's moment. JAMA. 2024;332(23):1969-1970.
[13] Update on buprenorphine for treatment of opioid-use disorder. July 2023. https://www.worstpills.org/newsletters/view/1544. Worst Pills, Best Pills News. Accessed February 4, 2025.
[14] Drug Profile: methadone. August 31, 2024. https://www.worstpills.org/monographs/view/127. Accessed February 4, 2025.
[15] Mallinckrodt. Label: methadone (METHADOSE). December 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/017116s045lbl.pdf. Accessed February 4, 2025.
