In March and October 2015, the Drug Enforcement Administration (DEA) and CDC, respectively, issued nationwide alerts identifying illicitly manufactured fentanyl (IMF) as a threat to public health and safety (1,2). IMF is unlawfully produced fentanyl, obtained through illicit drug markets, includes fentanyl analogs, and is commonly mixed with or sold as heroin (1,3,4). Starting in 2013, the production and distribution of IMF increased to unprecedented levels, fueled by increases in the global supply, processing, and distribution of fentanyl and fentanyl-precursor chemicals by criminal organizations (3). Fentanyl is a synthetic opioid 50–100 times more potent than morphine (2).* Multiple states have reported increases in fentanyl-involved overdose (poisoning) deaths (fentanyl deaths) (2). This report examined the number of drug products obtained by law enforcement that tested positive for fentanyl (fentanyl submissions) and synthetic opioid–involved deaths other than methadone (synthetic opioid deaths), which include fentanyl deaths and deaths involving other synthetic opioids (e.g., tramadol). Fentanyl deaths are not reported separately in national data. Analyses also were conducted on data from 27 states† with consistent death certificate reporting of the drugs involved in overdoses. Nationally, the number of fentanyl submissions and synthetic opioid deaths increased by 426% and 79%, respectively, during 2013–2014; among the 27 analyzed states, fentanyl submission increases were strongly correlated with increases in synthetic opioid deaths. Changes in fentanyl submissions and synthetic opioid deaths were not correlated with changes in fentanyl prescribing rates, and increases in fentanyl submissions and synthetic opioid deaths were primarily concentrated in eight states (high-burden states). Reports from six of the eight high-burden states indicated that fentanyl-involved overdose deaths were primarily driving increases in synthetic opioid deaths. Increases in synthetic opioid deaths among high-burden states disproportionately involved persons aged 15–44 years and males, a pattern consistent with previously documented IMF-involved deaths (5). These findings, combined with the approximate doubling in fentanyl submissions during 2014–2015 (from 5,343 to 13,882) (6), underscore the urgent need for a collaborative public health and law enforcement response.

Data were analyzed from four sources: 1) fentanyl submission data from the DEA National Forensic Laboratory Information System (NFLIS), which systematically collects drug identification results from drug cases submitted for analysis to forensic laboratories§; 2) synthetic opioid deaths, calculated using the National Vital Statistics System multiple cause-of-death mortality files¶; 3) national and state fentanyl prescription data that are estimated from IMS Health’s National Prescription Audit collecting 87% of retail prescriptions in the United States**; and 4) medical examiner/coroner reports or death certificate data from states with a high burden of synthetic opioid deaths (i.e., a 1-year increase in synthetic opioid deaths exceeding two per 100,000 residents, or a 1-year increase of ≥100 synthetic opioid deaths during 2013–2014). Synthetic opioid deaths were identified using the following International Classification of Diseases, 10th Revision codes: 1) an underlying cause-of-death code of X40–44 (unintentional), X60–64 (suicide), X85 (homicide), or Y10–Y14 (undetermined intent) and 2) a multiple cause-of-death code of T40.4. In 2014, any information on the specific drug or drugs involved in a drug overdose were reported for approximately 80% of drug overdose deaths; this proportion varied over time and by state (7). State analyses were limited to 27 states meeting the following criteria: 1) >70% of drug overdose deaths reported at least one specific drug in 2013 and 2014; 2) the change in the percentage of overdose deaths reporting at least one specific drug from 2013 to 2014 was <10%††; 3) ≥20 synthetic opioid deaths occurred during 2013 and 2014; and 4) fentanyl submissions were reported in 2013 and 2014.§§ These 27 states accounted for 75% of synthetic opioid deaths in the United States in 2014. Analyses compared changes in the crude rate of fentanyl submissions, fentanyl prescriptions, and synthetic opioid deaths during 2013–2014 using Pearson correlations. States were classified as high-burden if they experienced a 1-year increase in synthetic opioid deaths exceeding two per 100,000 residents or a 1-year increase of ≥100 synthetic opioid deaths during 2013–2014. Additional evidence from published state medical examiner/coroner or death certificate reports was reviewed to understand whether increases in synthetic opioid deaths were being primarily driven by fentanyl deaths and not by other synthetic opioids. Demographic characteristics of synthetic opioid deaths for high-burden and low-burden states were described.

During 2013–2014, fentanyl submissions in the United States increased by 426%, from 1,015 in 2013 to 5,343 in 2014, and synthetic opioid deaths increased by 79%, from 3,105 in 2013 to 5,544 in 2014.¶¶ In contrast, fentanyl prescription rates remained relatively stable (Figure 1). Although changes in fentanyl submissions and synthetic opioid death rates from 2013–2014 among the 27 states were highly correlated (r = 0.95) (Figure 2), changes in state-level synthetic opioid deaths were not correlated with changes in fentanyl prescribing (data not shown). During 2013–2014, the synthetic opioid crude death rate in the eight high-burden states increased 174%, from 1.3 to 3.6 per 100,000, and the fentanyl submissions rate increased by 1,000% from 0.5 to 5.5 per 100,000 (Table). Six of the eight high-burden states reported increases in synthetic opioid death rates exceeding 2.0 per 100,000 population, and seven states reported increases in deaths of ≥100.*** The eight high-burden states were located in the Northeast (Massachusetts, Maine, and New Hampshire), Midwest (Ohio), and South (Florida, Kentucky, Maryland, and North Carolina). Six of the eight states published data on fentanyl deaths from 2013 and 2014.††† Combining results across the state reports, total fentanyl deaths during 2013–2014 increased by 1,008, from 392 (2013) to 1,400 (2014), and the increase in total fentanyl deaths was of nearly the same magnitude as the increase in 966 synthetic opioid deaths in these states (589 [2013], 1,555 [2014]). This finding indicates that increases in fentanyl deaths were driving the increases in synthetic opioid deaths in these six states. Among high-burden states, all demographic groups experienced substantial increases in synthetic opioid death rates. Increases of >200% occurred among males (227%); persons aged 15–24 years (347%), 25–34 years (248%), and 35–44 (230%) years; Hispanics (290%), and persons living in large fringe metro areas (230%).§§§ The highest rates of synthetic opioid deaths in 2014 were among males (5.1 per 100,000); non-Hispanics whites (4.6 per 100,000); and persons aged 25–34 years (8.3 per 100,000), 35–44 years (7.4 per 100,000), and 45–54 years (5.7 per 100,000) (Table).