Initiation and dose of methadone monotherapy versus combination therapy, 2015 to 2023

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Background

The increased potency of the fentanyl-dominated drug supply has precipitated a shift in patient-reported opioid tolerance and methadone prescribing guidance. However, adoption of new methadone prescribing approaches remains unknown.

Objective

This study examined methadone initiation trends within the context of changing prescribing guidance and an increasingly volatile unregulated drug supply.

Methods

We conducted a retrospective, population-based repeated cross-sectional analysis among a cohort of methadone initiations captured between January 1, 2013, and July 31, 2023, in Ontario, Canada to examine methadone prescribing trends during the first 14 days of treatment.

Results

In this repeated cross-sectional study of 70 564 initiations of methadone monotherapy and 3069 initiations of combination therapy among 35 309 unique individuals, there was a shift toward methadone initiation at 30 mg in 2018, with subsequent attainment of higher doses within 2 weeks. The release of new methadone prescribing guidance further accelerated treatment initiation at higher doses and in combination with slow-release oral morphine; however, provision of subsequent dose titration significantly declined over time.

Conclusion

These findings suggest that the limited provision of rapid dose titration represents a potential missed opportunity for faster attainment of therapeutic doses.

Additional Resources

Citation

Garg R, Lou J, Bozinoff N, Beth S, Antoniou T, Wyman J, Munro C, Gomes T. (2025). Initiation and dose of methadone monotherapy versus combination therapy, 2015 to 2023. JAMA Network Open.

Date Released:

August 15, 2025

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