Document Type
Article
Publication Date
1-6-2026
Abstract
Purpose of Review: The potency of illicit fentanyl has rendered standard methadone inductions inadequate for many hospitalized adults with opioid use disorder. Standard protocols often fail to achieve therapeutic doses quickly enough to manage withdrawal and cravings in fentanyl-tolerant individuals, contributing to poor retention and higher self-discharge rates. This review examines emerging evidence on dosing strategies, outcomes, and safety of rapid methadone inductions in acute-care hospitals. Recent Findings: Nine studies (five retrospective cohorts, four case series/reports) encompassing 380 patients met inclusion criteria. Median starting doses were 30–40 mg (range 20–90 mg), with daily or symptom-triggered increases achieving 60–100 mg within 5–7 days—substantially faster than outpatient schedules. Sedation occurred in 6.4% of patients, while severe sedation requiring naloxone or ICU transfer was rare (0.4%). No in-hospital deaths, malignant arrhythmias, or torsades de pointes were reported. The only study assessing post-discharge outcomes found no overdoses within 30 days. Rapid titration improved retention, with self-discharge against medical advice ranging from 4 to 19% overall and significantly lower among pregnant patients than with slower titration (23.0% vs. 37.9%). Pregnant individuals, those with infections, and polysubstance users tolerated rapid induction without excess adverse events. Summary: Observational data suggest that rapid inpatient methadone titration can safely and effectively reach therapeutic doses within one week, even in fentanyl-tolerant patients. The approach may enhance hospital retention and facilitate smoother transitions to outpatient care. Controlled prospective trials are necessary to determine optimal dosing algorithms, monitor adverse effects, and assess long-term outcomes following discharge.
Recommended Citation
Berisha, Lorik; Patel, Sapan; Pirquet, Charlotte; Kumar, Navina Magesh; Soliman, Yousef; Ullah, Ahsan; and Matassa, Daniel M., "Rapid Inpatient Methadone Induction in the Fentanyl Era: A Systematic Review of Safety, Efficacy, and Protocols for Hospitalized Patients with Opioid Use Disorder" (2026). Division of Internal Medicine Faculty Papers & Presentations. Paper 73.
https://jdc.jefferson.edu/internalfp/73
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English


Comments
This article is the author's final published version in Current Addiction Reports, Volume 13, Issue 1, 2026, Article Number 5.
The published version is available at https://doi.org/10.1007/s40429-025-00701-3. Copyright © The Author(s) 2025.