Optimizing methadone treatment strategies for opioid use disorder in the era of fentanyl

PROJECT SUMMARY Treatment with medications for opioid use disorder is a critical intervention with proven effectiveness for improving morbidity, mortality and quality of life, yet only a minority of patients with an opioid use disorder are engaged in treatment and ongoing use of fentanyl during treatment is common. Current methadone treatment protocols were developed and validated based on studies performed in populations with heroin use, with a focus on diversion prevention and minimizing overdose risk. A deadlier drug supply dominated by fentanyl has altered this risk-benefit assessment and evidence-based updates are urgently needed. Challenges of methadone initiation and maintenance in patients with fentanyl use are well-documented. Inadequate control of withdrawal and cravings at standard methadone doses due to higher levels of opioid tolerance and physical dependence in individuals with a history of fentanyl use may contribute to ongoing use of non-prescribed opioids and increased overdose risk. Failure to reach a therapeutic dose expediently can result in a perceived lack of efficacy, adding additional barriers to treatment engagement and retention. In response, some addiction medicine specialists have suggested that accelerated initiation trajectories combined with higher maintenance doses are needed, but there are no standardized protocols for patients using fentanyl and wide variability in methadone dispensing practice. Limited data suggest that higher doses and expanded 'take-homes' among people with a history of fentanyl use do not contribute to excess deaths from methadone, but these studies lack longitudinal patient-level effectiveness and safety data to draw firm conclusions to support practice change. This study seeks to evaluate the effectiveness and safety of different methadone treatment strategies, including dosing and expanded take- home flexibilities associated with the COVID-19 pandemic, on treatment retention and non-fatal/fatal overdose in a retrospective cohort of patients (n~10,000) initiating medication treatment for an opioid use disorder with methadone in the fentanyl era. The data-rich environment in Rhode Island and established relationships with non-profit opioid treatment programs and state agencies will be leveraged to assemble a single, comprehensive, longitudinal novel dataset that will include both electronic health record data (detailed patient characteristics and methadone dispensing data) and state administrative data (with emergency medical services and emergency department visits for non-fatal opioid overdose, medical examiner records for fatal overdoses, corrections, and controlled substance prescribing information) Results of this study will help resolve long-standing questions about the optimal methadone dosing strategies and directly inform opioid use disorder clinical treatment best practices for patients who use fentanyl, thereby reducing the risk of overdose and improving treatment retention.