Reducing Overdose and Suicide Risk in Individuals with OUD and Co-occurring Disorders - PROJECT ABSTRACT Suicide and overdose deaths are at record levels, and the Emergency Department (ED) is at the forefront of delivering care to those at the highest risk. Opioid use disorders (OUD) and mental illness are major contributors to both. In 2017 nearly half of suicide and overdose deaths were linked to opioid use, with the highest death rates seen in people with both OUD and mental illness. Medications for OUD (MOUD) saves lives, and substantial research has documented the dose-response relationship between retention in MOUD care, all-cause mortality, and suicide/overdose. The California Bridge Program (CA Bridge) is the largest ED- based addiction treatment implementation project in the US; the primary goal is to improve MOUD access and linkage to outpatient care for patients with OUD. However, data from the first 52 hospitals suggest that over 60% of patients had not filled an outpatient MOUD prescription two weeks after the ED visit; national data suggest that even when patients start MOUD, many discontinue treatment, putting them at increased risk of relapse, overdose, and death. Given finite resources, ED providers need evidence-based guidance about the optimal way to manage patients where there is both between-person heterogeneity (despite being offered services many patients do not access them) and within-person heterogeneity (even when MOUD is initiated many patients discontinue treatment), and information about whether patients with a prior history of either overdose or a co-occurring mental illness should receive a different sequence of interventions. This combination of between- and within-person heterogeneity, suggests the need for an adaptive intervention (AI) approach, whereby MOUD service-delivery interventions are adapted based on the patient’s initial presentation and changing status. We propose a Sequential Multiple Assignment Randomized Trial to inform the development of an AI that is optimally effective in increasing buprenorphine use for adults presenting to the ED with an OUD-related event. Our primary outcome is the number of days a prescription for buprenorphine was filled in the 6 months following the initial ED visit. Our pre-specified secondary outcome is a composite measure of the time between ED presentation and subsequent overdose or suicide events, including death. To conduct the study, we leverage a partnership between RAND, UCLA, Stanford and two hospitals that were early adopters of CA Bridge. ED providers typically provide time-limited care for acute problems in the ED, forcing an unrealistic and high-stakes hand off during a critical transition point. Testing different service- delivery interventions and proactively addressing the key nature of this transition, is innovative and puts forward a new vision of ED care. Our study is aligned with NIDA’s priorities as outlined in NOT-NS-20-005 and will provide definitive answers to multiple critical questions, necessary for building an optimal AI that has the potential to increase long-term MOUD use and save lives being lost to overdose, suicide, and untreated OUD.