Discussion

This analysis of opioid overdose deaths in 10 states participating in the ESOOS program found that illicitly manufactured fentanyl is a key factor driving opioid overdose deaths and that fentanyl analogs are increasingly contributing to a complex illicit opioid market with significant public health implications. Previous reports have indicated that use of illicitly manufactured fentanyl mixed with heroin, with and without users’ knowledge, is driving many fentanyl overdoses, particularly east of the Mississippi River (3,4). Consistent with these findings, at least half of opioid overdose deaths in six of the seven participating states east of the Mississippi tested positive for fentanyl. Over half the overdose deaths involving fentanyl and fentanyl analogs tested positive for confirmed or suspected heroin (the most commonly detected illicit substance), cocaine, or methamphetamine. This supports findings from other reports indicating that fentanyl and fentanyl analogs are commonly used with or mixed with heroin or cocaine (3,4). Nearly half of overdose deaths involving fentanyl and fentanyl analogs, however, did not test positive for other illicit opioids, suggesting that fentanyl and fentanyl analogs might be emerging as unique illicit products.

Fentanyl and fentanyl analogs are highly potent and fast-acting synthetic compounds that can trigger rapid progression to loss of consciousness and death and thus might require immediate treatment and high doses of naloxone (5). Because of the potency of fentanyl and fentanyl analogs and the rapid onset of action, these drugs were determined by medical examiners and coroners to play a causal role in almost all fatal opioid overdoses in which they were detected. Injection, the most commonly reported route of administration in fatal overdoses, exacerbates these risks because of rapid absorption and high bioavailability. The high potency of fentanyl and fentanyl analogs, however, can result in overdose even when administered via other routes. Nearly one in five deaths involving fentanyl and fentanyl analogs had evidence of snorting, ingestion, or smoking, with no evidence of injection. Multiple overdose outbreaks and law enforcement drug product submissions across the country have reported counterfeit prescription pills laced with fentanyl and fentanyl analogs (10).

With few exceptions, fentanyl analogs are illicitly manufactured, because they do not have a legitimate medical use in humans.§§ The detection of fentanyl analogs in >10% of opioid overdoses in four states raises the concern that fentanyl analogs have become a part of illicit opioid markets in multiple states. The fentanyl analogs most commonly detected were carfentanil, furanylfentanyl, and acetylfentanyl. Carfentanil, which is intended for sedation of large animals, is much more potent than fentanyl, whereas furanylfentanyl and acetylfentanyl are less potent (9). Carfentanil contributed to approximately 350 overdose deaths in Ohio, but was detected in only one other state (West Virginia). Because of its extreme potency, even limited circulation of carfentanil could markedly increase the number of fatal overdoses. Recent data suggest that carfentanil deaths are occurring in multiple other states, including Kentucky, which reported 10 overdose deaths involving carfentanil in the second half of 2016 (Kentucky Department of Public Health, unpublished data, 2017) and New Hampshire, which reported 10 deaths in 2017.¶¶ Forty-six percent of SUDORS opioid overdose deaths involving fentanyl analogs tested positive for fentanyl or an additional fentanyl analog, ranging from 31% for carfentanil to 97% for acetylfentanyl. The increased mixing or co-use of fentanyl, heroin, cocaine, and varying fentanyl analogs might contribute to increased risk for overdose because persons misusing opioids and other drugs are exposed to drug products with substantially varied potency.

The findings in this report are subject to at least five limitations. First, results are limited to 10 states and therefore might not be generalizable. Second, the presence of fentanyl analogs is underestimated because commonly used toxicologic testing does not include fentanyl analogs, some fentanyl analogs are difficult to detect (9), and specialized testing for fentanyl analogs varied across states and over time. Third, the route of fentanyl and fentanyl analog administration must be interpreted cautiously because the data do not link specific drugs to routes of administration and thus the precise route of administration of fentanyl or fentanyl analogs cannot be determined in overdose deaths involving multiple substances (e.g., heroin and cocaine) and routes (e.g., injection and snorting). Fourth, the combination of deaths with toxicologic confirmation of heroin with those with detection of morphine and death scene evidence suggesting heroin use might have resulted in misclassification of some deaths. Finally, fentanyl source could not be definitively determined; however, only a small percentage of fentanyl deaths had evidence consistent with prescription fentanyl (e.g., transdermal use versus injection).

Illicitly manufactured fentanyl is now a major driver of opioid overdose deaths in multiple states, with a variety of fentanyl analogs increasingly involved, if not solely implicated, in these deaths. This finding raises concern that in the near future, fentanyl analog overdose deaths might mirror the rapidly rising trajectory of fentanyl overdose deaths that began in 2013 and become a major factor in opioid overdose deaths. In response to this concern, CDC expanded ESOOS to 32 states and the District of Columbia in 2017 and added funding for all 33 recipients to improve forensic toxicologic testing of opioid overdose deaths to include capacity to test for a wider range of fentanyl analogs.*** Increased implementation of evidence-based efforts targeting persons at high risk for illicit opioid use, including increased access to medication-assisted treatment, increased availability of naloxone in sufficient doses, and other innovative intervention programs targeting this group, is needed to address a large and growing percentage of opioid overdose deaths involving fentanyl and fentanyl analogs.