High-Dose Medications for Opioid Use Disorder: Effects on Treatment Retention, Drug Use Patterns, and Overdose Risks Amidst the Fentanyl Crisis

Massachusetts General Hospital, Boston MA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT The ongoing overdose crisis in the US, primarily driven by fentanyl, calls for innovative secondary overdose prevention strategies to improve engagement with medications for opioid use disorder (MOUD). Research suggests individuals using fentanyl may require faster or less challenging titration and higher maintenance doses due to their greater opioid tolerance, which differs from the needs of patients using prescription opioids or heroin, the populations for whom MOUD was initially developed. However, regulatory and structural challenges in the US hinder the implementation and rigorous evaluation of such MOUD dosing strategies. Building on our decade-long track record of collaboration, we propose an international collaborative effort to evaluate novel MOUD dosing strategies. We will leverage the Vancouver Injection Drug Users Study (VIDUS), one of the largest and longest-running prospective cohort studies of community-recruited people who use drugs in the world. The VIDUS well represents sub-sets of MOUD patients who bear a disproportionate burden of overdose (e.g., those unstably housed). While Canada faces a similar fentanyl-driven overdose crisis, its more relaxed MOUD regulations have allowed prescribers to implement novel dosing strategies. Further, VIDUS’ comprehensive dataset integrates rich longitudinal behavioral data (e.g., drug use patterns, nonfatal overdoses) with urine drug screen results and linked administrative databases (e.g., health insurance records, pharmacy dispensations, hospital/emergency room admissions, and fatal overdoses), overcoming major limitations in the US datasets and enabling rigorous evaluation of novel MOUD dosing strategies. Our proposal falls under Funding option A: Implement and rigorously evaluate strategies, with three specific aims. Aim 1 is to assess the impact of dosing strategies (i.e., rapid methadone titration, low-dose buprenorphine induction, and higher maintenance doses) on treatment retention, using marginal structural models. Aim 2 is to evaluate whether these dosing strategies reduce illicit drug use and the risks of nonfatal and fatal overdoses, using a comparative interrupted time series design. Aim 3 is to identify barriers and facilitators to adoption, feasibility, and scalability of the dosing strategies in the US through a targeted literature review, natural language processing analysis of social media data, and qualitative interviews with MOUD prescribers. It is designed to ensure that the evidence generated from Canadian settings can effectively inform the adaptation of dosing strategies into US healthcare systems. This project is timely, as there is growing recognition in the US that MOUD guidelines may need adaptation to better address challenges posed by the fentanyl crisis. By addressing challenges with MOUD engagement and overdose prevention, this study aligns with the CDC’s priority to implement and evaluate innovative secondary prevention strategies for reducing opioid-related harm. Our interdisciplinary team, including experts in addiction medicine, causal inference, and data science, is uniquely positioned to contribute insights that will shape future MOUD treatment strategies.