Timing of Initiation of Methadone Take-Home Dosing

Importance: Daily witnessed ingestion in community-based pharmacies is standard practice for methadone maintenance treatment for opioid use disorder in British Columbia, Canada. Whether this practice, compared with take-home methadone, may pose a barrier to sustained retention in treatment and its lifesaving benefits is not known. Objective: To assess the different initiation times of methadone take-home doses in terms of time to all-cause mortality and methadone discontinuation, defined as a gap in prescribed doses lasting 5 or more days. Design, Setting, and Participants: This cohort study using principles of target trial emulation used observational data from British Columbia, Canada, 2010-2022. Both incident (no history of opioid agonist treatment [OAT]) and prevalent new-user (no OAT within the past month) designs were used. The study included individuals aged 18 years or older who completed OAT induction, were not pregnant or incarcerated, and had no history of cancer treatment or palliative care. Data analyses were conducted from March 5, 2025, to May 29, 2026. Exposure: Exposure strategies were (1) no take-home dosing, (2) take-home dose initiation within 0 to 4 weeks after completing induction, (3) take-home dose initiation within 5 to 12 weeks after completing induction, (4) take-home dose initiation within 13 to 24 weeks after completing induction, and (5) take-home dose initiation within 25 to 52 weeks after completing induction. Main Outcomes and Measures: Outcomes were time to all-cause mortality and methadone discontinuation. A clone-censor-weight approach was used to estimate the 78-week adjusted risk difference (ARD). Results: A total of 9788 incident users (median age, 34.1 [IQR, 27.2-44.1] years; 32.8% female) and 31 658 prevalent new users (median age, 36.9 [IQR, 29.7-46.2] years; 33.3% female) were included. Compared with no take-home dosing in prevalent new-user analysis, ARDs for the mortality outcome were -0.87 (95% CI, -1.51 to -0.23) for take-home dose initiation within 0 to 4 weeks after completing induction, -0.98 (95% CI, -1.62 to -0.33) for take-home dose initiation within 5 to 12 weeks after completing induction, -0.82 (95% CI, -1.59 to -0.06) for take-home dose initiation within 13 to 24 weeks after completing induction, and -0.31 (95% CI, -1.05 to 0.44) for take-home dose initiation within 25 to 52 weeks after completing induction. Compared with no take-home dosing in prevalent new-user analysis, the discontinuation outcome ARDs were -2.04 (95% CI, -3.99 to -0.10) for take-home dose initiation within 0 to 4 weeks after completing induction, -5.29 (95% CI, -6.82 to -3.76) for take-home dose initiation within 5 to 12 weeks after completing induction, -5.97 (95% CI, -7.16 to -4.78) for take-home dose initiation within 13 to 24 weeks after completing induction, and -4.39 (95% CI, -5.37 to -3.42) for take-home dose initiation within 25 to 52 weeks after completing induction. Similar patterns were observed among incident users. Multiple sensitivity analyses with sample restrictions, time-0 classifications, timeline restrictions, and addressing residual confounding bias supported the primary results. Conclusions and Relevance: Results of this study suggest that initiating take-home methadone within 5 to 12 weeks and 13 to 24 weeks after completing induction resulted in the greatest benefits in reducing mortality and treatment discontinuation, although any take-home dosing was consistently better than no take-home dosing. These client-level benefits warrant consideration when refining clinical guidelines on take-home dosing.