Differential Impacts of Methadone and Buprenorphine/Naloxone on Pain-Related Outcomes Among People With Non-Heroin Opioid Use Disorder: Secondary Analyses From a Pragmatic Canadian Multisite Trial

Drug Alcohol Rev. 2026 Jul;45(5):e70190. doi: 10.1111/dar.70190.

ABSTRACT

INTRODUCTION: In addition to their use as opioid agonist therapy (OAT), methadone and buprenorphine/naloxone also have analgesic properties. However, there is limited information on the relative effectiveness of these medications for analgesia in the context of treatment for non-heroin opioid use disorder (OUD). This study estimated the impact of type of OAT on pain among individuals with non-heroin OUD.

METHODS: Using data from OPTIMA, a Canadian, randomised, 24-week clinical trial comparing buprenorphine/naloxone (via take-home doses) to methadone (via daily witnessed ingestion) for the treatment of non-heroin OUD, we evaluated the impact of type of OAT on pain outcomes (measured by the Brief Pain Inventory) among participants with major pain at baseline.

RESULTS: Mean pain severity scores significantly decreased in both arms over 24 weeks (methadone 4.89-2.16, buprenorphine/naloxone 4.94-1.08). There was a time by arm interaction, suggesting better performance of buprenorphine/naloxone up to week 9, and methadone afterwards. Mean pain-related function scores also significantly decreased over time (methadone 5.31-2.70, buprenorphine/naloxone 5.56-3.37), with no significant differences in overall scores between arms (p = 0.675). Methadone was associated with higher odds of achieving both pain severity and pain-related function response at week 24 (30% reduction in pain scores from baseline).

DISCUSSION AND CONCLUSIONS: Among people with non-heroin OUD initiating OAT, both methadone and buprenorphine/naloxone were associated with improvements in pain outcomes. However, methadone was associated with a higher likelihood of achieving pain severity and functional treatment response at week 24. These findings suggest the need to consider the type of OAT in the shared-decision making process for people with non-heroin OUD and comorbid pain.

PMID:42313747 | DOI:10.1111/dar.70190