The findings of this comparative effectiveness study provide insight into the high-risk and understudied population of individuals with OUD and cooccurring SUDs during a time when the opioid overdose epidemic is evolving into a polysubstance use crisis. We found that individuals with OUD and polysubstance use had a lower distribution of buprenorphine initiation even though buprenorphine demonstrated potentially more robust protective associations against acute drug-related events compared with ER naltrexone. Targeted efforts are needed to expand access to MOUD in individuals with polysubstance use.
