What is already known about this topic?
Synthetic opioids, including illicitly manufactured fentanyls (IMFs), were involved in 64% of >100,000 estimated U.S. drug overdose deaths during May 2020–April 2021.
What is added by this report?
During 2019–2020, IMF-involved overdose deaths increased sharply in midwestern, southern, and western jurisdictions. During 2020, approximately 40% of IMF-involved deaths also involved stimulants, and 56% of decedents had no pulse when first responders arrived. Injection drug use was reported in 25% of deaths, and noninjection routes of drug use in 27% of deaths.
What are the implications for public health practice?
Adapting overdose prevention and response efforts to address risk factors associated with IMFs and using innovative approaches to address the endemic nature of IMFs, various routes of IMF use, and frequent polysubstance use could slow increases in IMF-involved deaths.