Trends in and Characteristics of Drug Overdose Deaths Involving Illicitly Manufactured Fentanyls

Abstract and Introduction

Introduction

During May 2020–April 2021, the estimated number of drug overdose deaths in the United States exceeded 100,000 over a 12-month period for the first time, with 64.0% of deaths involving synthetic opioids other than methadone (mainly illicitly manufactured fentanyls [IMFs], which include both fentanyl and illicit fentanyl analogs).* Introduced primarily as adulterants in or replacements for white powder heroin east of the Mississippi River,^[1] IMFs are now widespread in white powder heroin markets, increasingly pressed into counterfeit pills resembling oxycodone, alprazolam, or other prescription drugs, and are expanding into new markets, including in the western United States^†.^[2] This report describes trends in overdose deaths involving IMFs (IMF-involved deaths) during July 2019–December 2020 (29 states and the District of Columbia [DC]), and characteristics of IMF-involved deaths during 2020 (39 states and DC) using data from CDC’s State Unintentional Drug Overdose Reporting System (SUDORS). During July 2019–December 2020, IMF-involved deaths increased sharply in midwestern (33.1%), southern (64.7%), and western (93.9%) jurisdictions participating in SUDORS. Approximately four in 10 IMF-involved deaths also involved a stimulant. Highlighting the need for timely overdose response, 56.1% of decedents had no pulse when first responders arrived. Injection drug use was the most frequently reported individual route of drug use (24.5%), but evidence of snorting, smoking, or ingestion, but not injection drug use was found among 27.1% of decedents. Adapting and expanding overdose prevention, harm reduction, and response efforts is urgently needed to address the high potency,^[3] and various routes of use for IMFs. Enhanced treatment for substance use disorders is also needed to address the increased risk for overdose^[4] and treatment complications^[5] associated with using IMFs with stimulants.

Death certificate data, postmortem toxicology testing results, and death scene and witness findings from medical examiner or coroner reports are entered into SUDORS for unintentional drug overdose deaths and those of undetermined intent in 48 participating jurisdictions, providing comprehensive details about overdose deaths across jurisdictions not available from other data sources.^[6] IMFs^§ were identified using toxicology and scene evidence.^[7] Monthly trends in IMF-involved deaths during July 1, 2019–December 31, 2020, were stratified by geographic region^¶ among 30 jurisdictions with complete data (26 reported all overdose deaths in the jurisdiction and four reported deaths from subsets of counties).** Differences in the proportions of overdose deaths that involved IMFs (comparing July–December 2019 with July–December 2020) were assessed using z-tests, with p-values <0.05 considered statistically significant. Decedent demographics, overdose characteristics, and other drug co-involvement, were examined among 40 jurisdictions using 2020 data (35 reported all overdose deaths in the jurisdiction and five reported deaths from subsets of counties), stratified by region.^†† Analyses were performed using SAS (version 9.4; SAS Institute). This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.^§§

IMF-involved deaths increased from July–December 2019 to July–December 2020 across regions: Northeast (3.5% relative increase; from 5,019 to 5,194 deaths), Midwest (33.1%; 1,510 to 2,010), South (64.7%; 2,636 to 4,342), and West (93.9%; 955 to 1,852) (Figure 1). The proportions of drug overdose deaths involving IMFs increased significantly in midwestern (12.2% relative increase; from 62.9% to 70.6%), southern (24.1%; 54.3% to 67.4%), and western (45.7%; 30.2% to 44.0%) jurisdictions, while remaining stable in the Northeast (1.3% increase; 79.8% to 80.8%).

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Number and percentage of drug overdose deaths involving illicitly manufactured fentanyls,* by month and geographic region^† — State Unintentional Drug Overdose Reporting System, 30 jurisdictions,^§ July 2019–December 2020
Abbreviations: IMFs = illicitly manufactured fentanyls; SUDORS = State Unintentional Drug Overdose Reporting System.
*Includes illicitly manufactured fentanyl and fentanyl analogs.
^† Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, Pennsylvania, Rhode Island, and Vermont; Midwest: Illinois, Kansas, Minnesota, Missouri, and South Dakota; South: Delaware, District of Columbia, Georgia, North Carolina, Oklahoma, Tennessee, Virginia, and West Virginia; West: Alaska, Arizona, Colorado, Montana, Nevada, New Mexico, Oregon, Utah, and Washington.
^§Illinois, Missouri, Pennsylvania, and Washington reported deaths from counties that accounted for ≥75% of drug overdose deaths in the state in 2017, per SUDORS funding requirements; all other jurisdictions reported deaths from the full jurisdiction.

Across regions, more IMF-involved deaths co-involved stimulants (40.1%–45.2%) than co-involved opioids other than IMFs (19.2%–31.6%) (Figure 2). Cocaine (25.5%–35.1%) and heroin (16.6%–22.3%) were the most commonly co-involved stimulant and opioid other than IMFs, respectively, among IMF-involved deaths in all regions except the West, where methamphetamine (25.3%) and prescription opioids (12.0%) were most common. Substantial proportions of IMF-involved deaths involved no other opioid or stimulant (Northeast: 39.7%; Midwest: 40.6%; South: 37.1%; West: 49.5%). Benzodiazepines, gabapentin, and xylazine, all nonopioids with sedative or hypnotic properties, were involved in 12.3%–15.5%, 2.7%–5.2%, and 0.1%–5.5% of IMF-involved deaths, respectively, across all regions.

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Co-involvement of other opioids, stimulants, and other psychoactive substances in drug overdose deaths involving illicitly manufactured fentanyls,* by geographic region^† — State Unintentional Drug Overdose Reporting System, 40 jurisdictions,^§ 2020^¶,**^,††
Abbreviations: IMFs = illicitly manufactured fentanyls; Rx = prescription; SUDORS = State Unintentional Drug Overdose Reporting System.
*Includes illicitly manufactured fentanyl and fentanyl analogs.
^† Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, Pennsylvania, Rhode Island, and Vermont; Midwest: Illinois, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, Ohio, and South Dakota; South: Arkansas, Delaware, District of Columbia, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, Tennessee, Virginia, and West Virginia; West: Alaska, Arizona, Colorado, Hawaii, Montana, Nevada, New Mexico, Oregon, Utah, and Washington.
^§Illinois, Louisiana, Missouri, Pennsylvania, and Washington reported deaths from counties that accounted for ≥75% of drug overdose deaths in the state in 2017, per SUDORS funding requirements; all other jurisdictions reported deaths from the full jurisdiction. Jurisdictions included if data were available for January–June or July–December 2020, or both.
^¶Deaths in the “no stimulant or opioid other than IMFs involved” category could have involved drugs other than opioids and stimulants. The “any opioids other than IMFs” category includes heroin, prescription opioids, and other illicit synthetic opioids (e.g., isotonitazene, U-47700). The “any stimulant” category includes cocaine, amphetamines, cathinones, and other central nervous system stimulants (e.g., atomoxetine, caffeine).
**Buprenorphine and methadone are included as prescription opioids; however, they are used both for treatment of pain and for treatment of opioid use disorder. Fewer than 3% of deaths involved buprenorphine, and fewer than 4% of deaths involved methadone, across jurisdictions.
^††Co-involvement of gabapentin and xylazine in IMF deaths is likely underestimated because of lack of routine postmortem toxicology testing for these drugs across jurisdictions.

Most IMF-involved deaths (73.0%) were among males (Table). In western jurisdictions, 21.8% of decedents were aged <25 years, whereas in other regions, 5.9%–8.7% of decedents were in this age group. Injection drug use was the most commonly reported route of drug use among all IMF-involved deaths in all regions (22.7%–30.6%), except the West (11.7%). Evidence of snorting, smoking, or ingestion, but not injection drug use, was reported in 57.1% of deaths in western jurisdictions and 19.2%–26.4% of deaths in other regions. For 48.3% of IMF-involved deaths, no evidence of route of drug use was documented. Counterfeit pill evidence^¶¶ was documented among 13.3% of deaths in the West and <1.0% in other regions. Approximately one half of decedents (56.1%) had no pulse when first responders arrived. Most deaths occurred at the decedent’s own home (64.2%) or in a house or apartment belonging to someone else (14.8%). Approximately one third (34.7%) of deaths occurred with a potential bystander*** present who did not respond to the overdose, most commonly because of spatial separation from the decedent (e.g., in a different room of the same house).