Evaluation of the Safety and Efficacy of Rapid Methadone Titration in Patients Being Treated for Opioid Use Disorder

BACKGROUND: Methadone rapid titration in the inpatient setting up to 100 mg has been described for withdrawal maintenance. Previous studies are variable in size for those completing rapid titration with limited safety, no efficacy analysis, and no analysis by prior methadone use. Objective of this study is to characterize safety and efficacy of rapid methadone titration beyond 60 mg daily. METHODS: This is a retrospective observational analysis of hospitalized adults with opioid use disorder undergoing methadone titration beyond 60 mg. Key exclusion criteria include patients receiving surgery. A historical cohort was also reviewed to compare previous titration methods prior to the addition of the Addiction Medicine consult team. Primary objective is characterizing safety events during rapid methadone titration, defined as QTc > 500 ms, Richmond Agitation-Sedation Scale < -1, escalation to intensive care unit, and naloxone use. Secondary objectives are management of withdrawal symptoms (Clinical Opiate Withdrawal Scale [COWS] < 5 or >15, non-methadone opioid use), incidence of patient-directed discharge, discharges to substance use facilities, 30-day readmission rates, and characterization of methadone titration. RESULTS: In the 32 patients included, 12 safety events occurred, and the overall rate of methadone titrate was 5.4 mg per day [interquartile range 4.2-6.8] with a faster titration of 6.8 mg per day [5.5-8.9] in patients restarting methadone. There was no significant relationship between safety events and the rate of methadone titration. Patients' withdrawal was managed throughout the study (COWS < 5) in at least 90% of patients. Sixty percent of patients were discharged to a substance use facility. CONCLUSION: Methadone was titrated rapidly with minimal occurrence of safety events and improvement in withdrawal symptoms.