Methadone Associated With Lower Risk of Treatment Discontinuation in Opioid Use Disorder

For patients with opioid use disorder (OUD), receiving methadone (Methadose, Dolophine) was associated with a lower risk of treatment discontinuation vs buprenorphine (Cizdol, Brixadi)/naloxone (Narcan). These findings are based off of a new comparative analysis published today in JAMA Network.¹

Methadone bottle | image credit: M.Rode-Foto - stock.adobe.com

Drug and Alcohol Dependence Reports estimates that between 2010 and 2019 there were 6.7 to 7.6 million adults living with OUD in the US; however, these approximations suffer from bias and could underestimate the true number of individuals with OUD by 3 to 5 times.² Furthermore, for adults in need of treatment for their condition, the CDC estimates that only 45.5% receive medication, with the need for OUD treatment varying among different groups and depending on employment status, poverty level, type of opioid used, and education, among other factors.³ 

The present authors looked at the international guidelines on opioid agonist treatment (OAT) for OUD and noticed that, due to lacking evidence that compares different treatments, the standing recommendations remain discordant.¹ For example, US guidelines fail to specifically recommend a first-line treatment, compared with Canada and British Columbia, where buprenorphine/naloxone is explicitly suggested as a primary intervention. This data deserves more attention, they added, as fentanyl overdoses have been on the rise coupled with insufficient clinical trials that venture outside heroin or prescribed opioids, or trials that investigate how effective OUD medications are across different demographics.

Consequently, they conducted a retrospective, observational, population-based study to assess the risk of treatment discontinuation and mortality for those with OUD treated with buprenorphine/naloxone vs methadone. Between January 2010 and March 2020, 9 linked administrative, population-level databases were used to gather data on individuals in British Columbia who received OAT. There were 2 parts of this analysis, an initiator analysis for those receiving OAT for the first time, as well as a per-protocol analysis to compare outcomes related to each treatment’s optimal dose.

There was a total of 30,891 people included in the initiator analysis and 25,614 people in the per-protocol analysis. Over 65% were males with a median age of 33 years (25-74 years). Furthermore, just over 12% lived in rural areas as well as reported housing instability in the last 5 years. In the year prior to the study, 7% had been incarcerated.

Among the initiator group, those receiving methadone were engaged in treatment for a median of 66 days (25th-75th, 9-371 days) before discontinuing vs 30 days (25th-75th, 7-127 days) for those receiving buprenorphine/naloxone. There was also a higher risk of discontinuation associated with buprenorphine/naloxone vs methadone (88.8% vs 81.5%; adjusted HR, 1.58; 95% CI, 1.53-1.63). A similar trend was observed for the optimal dosage of buprenorphine/naloxone vs methadone (42.1% vs 30.7%; HR, 1.67; 95% CI, 1.58-1.76) and these results were consistent throughout the variety of their analyses, the authors commented.

Mortality risk was low among incident users during their treatment, with less than 10 deaths recorded for those receiving buprenorphine/naloxone (0.08%; 8.1 per 1000 person-years) and less than 20 with methadone (0.13%; 18.8 per 1000 person-years).

“These results add to a growing evidence base consistent with methadone offering greater effectiveness in promoting sustained retention for individuals receiving OAT,” the authors concluded, commenting how these results were largely consistent after fentanyl arrived in illegal drug supplies.

“As the use of more potent synthetic opioids continues to increase in North America and elsewhere, clinical guidelines for all aspects of the treatment of people with opioid use disorders require reconsideration to reduce the risk of discontinuation of treatment.”

References

1. Nosyk B, Eun Min J, Homayra F, et al. Buprenorphine/naloxone vs methadone for the treatment of opioid use disorder. JAMA. Published online October 17, 2024. doi:10.1001/jama.2024.16954

2. Keyes KM, Rutherford C, Hamilton A, et al. What is the prevalence of and trend in opioid use disorder in the United States from 2010 to 2019? Using multiplier approaches to estimate prevalence for an unknown population size. Drug Alcohol Depend Rep. 2022;3:100052. doi:10.1016/j.dadr.2022

3. Dowell D, Brown S, Gyawali S. Treatment for opioid use disorder: Population estimates — United States, 2022. Updated June 27, 2024. Accessed October 17, 2024. https://www.cdc.gov/mmwr/volumes/73/wr/mm7325a1.htm#:~:text=The%20percentage%20of%20adults%20needing,other%20than%20opioids%20(61.2%25)