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Overdose deaths involving the synthetic opioid, illicitly-manufactured fentanyl (IMF), skyrocketed across the country from 2019 to 2020, researchers found.

Between July 2019 and December 2020, IMF-involved overdose deaths nearly doubled in the West (93.9%), increased 65% in the South and 33% in the Midwest, reported Julie O'Donnell, PhD, of the CDC's National Center for Injury Prevention and Control in New Orleans, and colleagues.

Moreover these deaths were quick, as 56% of people who died from an IMF-involved overdose did not have a pulse when first responders arrived on the scene, and approximately 40% of IMF-involved deaths also involved a stimulant, O'Donnell's group wrote in the .

These data follow a CDC report that estimated that more than 100,000 people died of a drug overdose in the U.S. from May 2020 to April 2021 -- the first time deaths surpassed 100,000 in a single year. Approximately 64% of those deaths involved synthetic opioids, which include IMFs.

Rapid increases in deaths related to IMFs "suggest increases in IMF distribution and exposure, consistent with law enforcement drug supply data," the authors noted.

O'Donnell and colleagues also noted that these data underscore the need for timely overdose response, and that stimulants can complicate substance abuse treatment and increase overdose risk.

They used data from the State Unintentional Drug Overdose Reporting System (SUDORS) to analyze monthly trends on overdose deaths involving IMFs, which included complete data from 30 states. The database included information from death certificates, postmortem toxicology testing, and coroner or medical examiner reports.

About three-quarters of the IMF-involved deaths occurred in men. In Western states, approximately 22% of IMF-involved deaths were in people younger than age 25, which was significantly higher than in other regions (6% to 9%). Overall, the fraction of drug overdose deaths involving IMFs increased by 12.2% in the Midwest, 22.1% in the South, and 45.7% in the West.

The only region where IMF-involved overdose deaths were stable was the Northeast, which saw a 3.5% increase in IMF-related deaths during the study period.

In all regions, more overdose deaths related to IMFs co-involved stimulants than other non-IMF opioids. Cocaine was the most common stimulant co-involved in 26%-35% of IMF-involved deaths, followed by heroin (17%-22%) in all regions except the West, where co-involvement of methamphetamine (25.3% of IMF-involved deaths) and prescription drugs (12% of deaths) were most frequently observed.

The most frequently reported route of IMF use was by injection (25%), however, the authors noted that evidence of snorting, smoking, or ingestion without injection was observed in 27% of deaths related to IMFs.

Once again, the West differed from other regions, with snorting, smoking or ingestion observed in 57.1% of IMF-involved deaths, while injection was only observed in 11.7% of deaths.

Interestingly, approximately 40% to 50% of all IMF-involved deaths in each region did not involve any other opioid or stimulant. Overall, route of use was not documented in nearly 50% of IMF-involved deaths.

O'Donnell and colleagues recognized that jurisdictions included in this study were not representative of the entire nation, and some states only reported subsets of counties. Additionally, death investigation differed by state and may account for regional differences in reporting.

The researchers also acknowledged that difficulties obtaining overdose characteristics may have contributed to an underestimation of deaths. Finally, there is no standard for postmortem toxicology testing, which could result in a failure to detect IMFs or other drugs.

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