Microdosing initiation of buprenorphine for people seeking treatment for opioid use disorder

ABSTRACT With the career goal of becoming an independent physician-investigator, Dr. Benjamin Hayes describes a mentored research project and a rigorous career development plan which will prepare him to study the testing of interventions to improve the health of people who use drugs (PWUD). The prevalence of opioid use disorder (OUD) in the US has resulted in a marked spike in overdose deaths. Buprenorphine (BUP) treatment for opioid use disorder (OUD) reduces illicit opioid use and opioid overdose mortality, yet remains greatly underutilized. The initiation of BUP remains a major barrier to treatment uptake. Two challenges that limit BUP use are: 1) patients must typically avoid opioids for 24-48 hours before starting BUP, which results in a period of planned withdrawal symptoms; and 2) patients may experience preciptitated withdrawal during BUP initiation if taken too soon. Research has suggested that both types of withdrawal deter people from starting BUP and are reasons for initiation drop-out. Our goal is to rigorously develop and pilot test a “microdosing” protocol that overcomes the phamacologic challenges of buprenorphine treatment initiation. Microdosing is the process of starting buprenorphine at doses low enough to not precipitate withdrawal and incrementally increasing to therapeutic doses, at which point the patient stops their use full agonist opioids. We hypothesize that microdosing will increase buprenorphine treatment initiation success by (1) avoiding the need to experience withdrawal, and (2) reducing the risk of precipitated withdrawal. Case studies suggest that microdosing is feasible and may minimize withdrawal, but no randomized control trials of buprenorphine microdosing inititian have established safety and effectiveness. In a 4-week randomized controlled trial, we propose to pilot test an innovative buprenorphine microdosing protocol vs. treatment as usual (TAU), defined as standard home initiation of buprenorphine treatment. We will randomize 70 people with OUD to microdosing or TAU, conduct study visits at baseline and weeks 1 and 4, and provide participants with mobile phones to collect rich electronic Ecological Momentary Assessment (EMA) data. This proposal aims to 1) determine preliminary effectiveness, feasibility and safety and 2) stakeholder experiences to plan for a fully powered, multi-site RCT; and 3) use the EMA data to investigate whether symptoms of withdrawal, anxiety, and cravings mediate initiation success. These will inform the design of a fully powered RCT to test the efficacy of BUP microdosing initiation and enrich the literature of barriers to BUP initiation. To accomplish these aims, Dr. Hayes will pursue training in randomized controlled trial design and conduct, qualitative methods and analysis, EMA design, conduct, and analysis, and scientific writing. With completion of these activities, along with intensive mentorship, Dr. Hayes will develop the skills necessary to achieve his career goal of becoming an independent investigator.