Methadone Dose and Patient-Directed Discharge in Hospitalized Patients With Opioid Use Disorder.

Importance: Patient-directed discharge (PDD), when patients leave the hospital prior to completing recommended medical treatment, is associated with increased morbidity and mortality and occurs in 10% to 20% of hospitalizations for patients with opioid use disorder (OUD). Understanding risk factors associated with PDD is essential to improving outcomes for this population. Objective: To investigate whether hospitalized patients with OUD who received higher doses of methadone during the first 24, 48, and 72 hours after first contact with the emergency department had decreased odds of PDD. Design, Setting, and Participants: This retrospective observational cohort study was conducted at a single academic health center in the northeastern US during the fentanyl era (July 1, 2019, to June 30, 2022). Hospitalized adults with OUD and without methadone listed in their medication history who received methadone during the first 72 hours were included. Data were analyzed from April 2025 through February 2026. Exposures: Cumulative dose of methadone received for patients 24, 48, and 72 hours after initial evaluation in the emergency department. Main Outcomes and Measures: PDD by 48, 72, or 96 hours or ever, as indicated by discharge disposition in the patient electronic health record. Results: A total of 554 patients were included in the study. For analysis, participants were separated into cohorts based on cumulative dose by 24 hours (325 patients), 48 hours (488 patients), and 72 hours (454 patients) after presentation to the emergency department, with the main analysis among patients in the 24-hour cohort. Among 325 patients (184 male [56.6%]; median [IQR] age, 49.0 [36.0-59.0] years) receiving methadone within 24 hours of presentation to the emergency department, the incidence of PDD was 45 patients (13.8%). In an adjusted logistic regression model, each additional 10 mg of methadone in the first 24 hours was associated with lower odds of PDD (adjusted odds ratio [aOR], 0.71; 95% CI, 0.44-0.98) at 48 hours. Results were similar for PDD at 72 hours (aOR, 0.68; 95% CI, 0.50-0.85), 96 hours (aOR, 0.72; 95% CI, 0.56-0.88), or ever (aOR, 0.79; 95% CI, 0.67-0.91) in the 24-hour cohort and qualitatively similar but with smaller decreases in odds or nonsignificant outcomes for cumulative methadone dose in the 48-hour cohort (eg, PDD at 96 hours: aOR, 0.91; 95% CI, 0.82-0.99) and nonsignificant outcomes in the 72-hour cohort (eg, PDD at 96 hours: aOR, 0.98; 95% CI, 0.89-1.06). Conclusions and Relevance: In this study, higher cumulative doses of methadone during the first 48 hours of care were associated with substantial reductions in the incidence of PDD. These findings suggest that early and adequate treatment of withdrawal with methadone may be associated with reduced PDD among hospitalized patients with OUD in the fentanyl era.