(175) Safety of Rapid Methadone Titration for Opioid Use Disorder in Hospitalized Patients: A Pilot Study

Trainee Involvement: Yes

Background:
Fentanyl use in opioid use disorder (OUD) is associated with high opioid tolerance and diminished effectiveness of methadone for withdrawal management [Buresh 2021]. Current methadone dosing guidelines recommend initiation at 10-30 mg/day with incremental dose increases of 5-10 mg every 3-5 days [SAMHSA, 2021]. However, we find this titration schedule is often inadequate in managing opioid withdrawal, and patients are discharged on a subtherapeutic dose of methadone. We investigate the safety and preliminary outcomes of a rapid methadone titration protocol in hospitalized patients with OUD.

Methods:
We implemented a pharmacist-guided protocol titrating methadone from 40 mg/day to 60/mg in 10 mg/day increments. Patients were hospitalized at an urban, academic tertiary-care hospital in Philadelphia, PA between September and October 2022. Data was abstracted from the electronic health record into a secure platform (REDCap). The primary outcome was safety, evaluated by the requirement for naloxone administration, presence of oversedation (RASS ≤ -3 or POSS ≥ 3), or development of QTc prolongation. Secondary outcomes included time to methadone initiation, methadone dose on discharge, frequency of patient directed discharge (PDD), and length of stay (LOS).

Results:
Patients (Nf11) were between 29 and 56 years of age (mean=41.2), consisted of 8 males (72.7%) and 3 females (27.3%), and primarily identified as white (63.6%). The median time from hospital admission to initiation of methadone was 3 days (range 0-26 days). Nine patients (81.8%) completed the protocol, with 2 PDDs prior to completion (18.2%). Naloxone administration and oversedation were not observed for any patients. No clinically significant increase in QTc or adverse cardiovascular events were observed. The mean methadone dose on discharge for completers was 72.8±7.9 mg. Median LOS was 9 days across all patients.

Discussion:
Rapid methadone titration has been previously, successfully implemented in an otherwise healthy clinic population [Stone, 2020]. Results of this pilot study support the conclusion that rapid methadone titration may be safe in certain medically hospitalized patients as well. No patients required naloxone administration, experienced oversedation, or demonstrated clinically significant QTc prolongation. Notably, a PDD of 18.2% with a median LOS of 9 days was observed, as compared to a recent study by our group (Nf23) demonstrating a baseline PDD rate of 69% and mean LOS of 3 days in patients with OUD [Thakrar, 2023].

Conclusion:
This pilot study provides preliminary support for safe, rapid methadone titration in hospitalized patients with OUD.

References:

Buresh M, et al. Adapting methadone inductions to the fentanyl era. J Subst Abuse Treat. 2022 Oct;141:108832.
Stone AC, et al. One year of methadone maintenance treatment in a fentanyl endemic area: Safety, repeated exposure, retention, and remission. J Subst Abuse Treat. 2020 Aug;115:108031.
Substance Abuse and Mental Health Services Administration (SAMHSA). (2021). Medications for Opioid Use Disorder Treatment Improvement Protocol (TIP) Series 63.
Thakrar AP, et al. Safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with opioid use disorder. Addict Sci Clin Pract. 2023 Feb 24;18(1):13.

<