(113) Two Cases of Rapid Titration of Methadone in the Hospital Setting

Introduction
Methadone is one of the life-saving treatments for Opioid Use Disorder (OUD), but given its long half-life, variable bioavailability and clearance, and lack of a ceiling effect, it is traditionally initiated at relatively low doses and increased slowly. At outpatient Opioid Treatment Programs (OTPs), the maximum total methadone dose on Day 1 is 40mg, and the dose can be increased typically no more than 5-10mg every 3-5 days. Methadone doses of at least 80mg have been shown to be most effective at controlling cravings and use of illicit opioids(1); with use of higher potency fentanyl increasing, higher doses of methadone may be needed(2). The long process of methadone titration can result in patients being undertreated for weeks to months, and in the inpatient setting, undertreatment is a significant reason for patients leaving without receiving necessary medical care(3). The hospital provides a highly monitored setting in which to initiate and increase methadone, potentially allowing patients to transition to an OTP at an already therapeutic dose. There have been reports of more rapid titration(4,5), but more evidence is needed.

Methods
We report case summaries of 2 patients admitted at Massachusetts General Hospital (MGH), who had a diagnosis of severe Opioid Use Disorder according to the DSM-5 criteria and were consulted on by the addiction medicine consult service and started on methadone.

Results
Patient 1 is a 38-year-old woman who received a total methadone dose of 50mg on Day 1, 70mg on Day 2, and 80mg on Day 3, and was ultimately discharged on Day 15 on a dose of 85mg. She did not have QTc prolongation > 500ms. Patient 2 is a 51-year-old woman who received a total methadone dose of 50mg on Day 1, 80mg on Day 2, 100mg on Day 3, and was ultimately discharged on Day 11 on a dose of 130mg. She did have QTc prolongation >500ms, which improved by discharge after discontinuation of QT-prolonging antibiotics. No adverse events occurred, including no respiratory depression or oversedation resulting from methadone. Both patients appreciated the increase in dose, and were connected to OTP directly at discharge.

Conclusions
Our approach of rapid titration of methadone in the hospital setting was borne out of patient-centered care. In all cases, doses were not only increased to treat opioid withdrawal symptoms and cravings, but emphasis was placed on subjective feedback from the patient on their goal dose. With the most worrisome complication being sedation and respiratory depression, care was taken to monitor for signs of sedation during daily examination, thus our method may only be feasible in closely monitored settings. Further research is needed to evaluate this approach, including a larger retrospective case series.

References:
1. Moderate- vs High-Dose Methadone in the Treatment of Opioid Dependence: A Randomized Trial | Addiction Medicine | JAMA | JAMA Network. https://jamanetwork-com.ezp-prod1.hul.harvard.edu/journals/jama/fullarticle/189103.
2. Bromley, L. et al. Methadone treatment for people who use fentanyl: Recommendations. 30.
3. Summers, P. J., Hellman, J. L., MacLean, M. R., Rees, V. W. & Wilkes, M. S. Negative experiences of pain and withdrawal create barriers to abscess care for people who inject heroin. A mixed methods analysis. Drug Alcohol Depend. 190, 200–208 (2018).
4. Turner, S. D., Lurie, E. & Nader, M. Rapid Methadone and Concurrent Slow-Release Oral Morphine Titration in a Pregnant Fentanyl User. Can. J. Addict. 12, 29–33 (2021).
5. Hemmons, P., Bach, P., Colizza, K. & Nolan, S. INITIATION AND RAPID TITRATION OF METHADONE IN AN ACUTE CARE SETTING FOR THE TREATMENT OF OPIOID USE DISORDER: A CASE REPORT. J. Addict. Med. 13, 408–411 (2019).