Methadone Rapid Restart

Overview

The usual treatment for opioid use disorder (OUD) is opioid agonist therapy (OAT) with either methadone or buprenorphine. These treatments are well-established, reduce the risk of fatal overdoses, and are considered the standard approach. However, current methadone guidelines were developed when most people were using heroin, which is far less potent than today's unregulated/illicit fentanyl supply. As a result, people who use fentanyl often need higher doses to feel stable. Because methadone must be started at low doses and increased slowly, it can take weeks before someone reaches an effective dose. This process becomes even longer when doses are missed, since treatment often needs to be restarted at a lower level. The Methadone Rapid Restart is a newer strategy designed to take ongoing fentanyl use into account. Early clinical experience and modelling suggest that many people who use fentanyl have high opioid tolerance and may be able to return to their previous stable methadone dose even after several missed days, without added safety risk. This approach has shown promise in small clinical settings, but it is not yet known whether it provides better outcomes than the standard methadone titration used today. This study will be testing whether this protocol to help rapidly restart people on Methadone is acceptable for patients and use the learning to guide a subsequent larger clinical trial.

Canada continues to see the ongoing effects of the illicit drug overdose in the last decade. Fentanyl and fentanyl analogues account for the majority illicit drug overdose deaths with the highest rate of opioid-related deaths in Canada occurring in British Columbia (BC). Despite this rapid rise in unregulated fentanyl use, treatment strategies for people who use unregulated fentanyl still rely on the opioid use disorder (OUD) treatment guidelines developed from research conducted in people using heroin, a relatively less potent opioid. Currently, methadone and buprenorphine are the recommended medications for opiate use disorder (MOUD). Methadone at higher doses (at least 60-120mg/day) has shown to have greater effectiveness and treatment retention as compared to lower dosages, based on studies with patient populations using heroin (Bromley et al. 2021). It therefore stands to reason that in the age of unregulated fentanyl, even higher doses of methadone are likely necessary to achieve optimal efficacy and retention rates. Despite this, the highest recommended starting dose of methadone is currently 40mg with a maximum of 15 mg increase every 3 days, for those with a known very high tolerance. As a result, it takes several weeks for people using unregulated fentanyl to reach an effective dose, which is further compounded by missed doses. It is also recommended that if 4 doses of methadone are missed, patients restart at at 50% of their previous dose or at 30-40mg, whichever is higher; and if 5 or more consecutive doses are missed, patients receive a full re-titration, starting from 30-40mg. However, emerging clinical and pharmacokinetic data suggest that, as long as opioid tolerance remains unchanged, methadone can be safely restarted at the same stable dose after missing 4-8 subsequent doses. The proposed study aims to determine the safety and efficacy of continuing maintenance dose methadone after 4-8 missed doses in people continuing to use unregulated fentanyl to meet their opioid needs.