Introduction

Provisional estimates indicate that drug overdose deaths (overdose deaths) increased in 2019 after a slight decrease from 2017 to 2018 (1,2).* Approximately two thirds of overdose deaths in 2018 involved an opioid, but the opioid types and combinations contributing to deaths are changing (1–3). For example, although overdose deaths involving prescription opioids and heroin decreased from 2017 to 2018, those involving synthetic opioids excluding methadone (primarily illicitly manufactured fentanyl [IMF]) and co-involving stimulants increased (2,3). Deaths co-involving cocaine and IMF, and involving psychostimulants with abuse potential (e.g., methamphetamine) with and without opioids have driven recent increases in stimulant-involved overdose deaths (3,4). The specific drugs and drug combinations involved in overdose deaths have implications for substance use disorder treatment regimens and outcomes, overdose prevention strategies (e.g., avoidance of using drugs when alone) (5), and overdose response (e.g., stimulant use can affect the response to administered naloxone) (6).

Targeting common fatal overdose circumstances with effective and promising public health interventions can prevent deaths (7). Examples include treating underlying substance use disorder (8), targeting important touchpoints to facilitate linkage to treatment (e.g., during treatment for a nonfatal drug overdose or upon release from incarceration) (9,10), providing mental health treatment (11), and expanding community naloxone distribution (12).

This report describes decedent demographic characteristics and circumstances surrounding overdose deaths during January–June 2019 among 25 jurisdictions participating in CDC’s State Unintentional Drug Overdose Reporting System (SUDORS),^† and it highlights the involvement of opioids and stimulants, separately and in combination.

Methods

Twenty-one jurisdictions participating in SUDORS reported all unintentional and undetermined intent overdose deaths that occurred during January–June 2019; four additional states reported overdose deaths in a subset of counties.^§,¶ Jurisdictions abstract data from death certificates and medical examiner/coroner reports, including death scene investigation findings and all drugs detected by postmortem toxicology testing. Detected drugs were classified as involved in (i.e., contributing to) overdose deaths if the medical examiner/coroner listed them as causing death on the death certificate or in the medical examiner/coroner report.**

Overdose deaths were grouped by opioid and stimulant involvement into four mutually exclusive categories: 1) opioids without stimulants, 2) opioids and stimulants, 3) stimulants without opioids, and 4) neither opioids nor stimulants. Also, overdose deaths were grouped into the 10 most frequently occurring mutually exclusive combinations of opioid type or types (illicitly manufactured fentanyls^†† [referred to as IMFs, which include fentanyl and fentanyl analogs], heroin,^§§ prescription opioids,^¶¶ other illicit synthetic opioids [e.g., U-47700]), and stimulant type or types (cocaine, methamphetamine, other illicit stimulants [e.g., MDMA], and prescription stimulants***). Overdose death combinations included deaths involving one drug type (e.g., involving IMFs without other opioid or stimulant involvement) and deaths involving two or more types (e.g., co-involved IMFs and cocaine), but did not reflect nonopioid, nonstimulant drug involvement (e.g., benzodiazepines). The following potential intervention opportunities (per evidence^††† in the medical examiner/coroner report) were assessed: 1) recent institutional release (<1 month),^§§§ 2) previous nonfatal overdose, 3) mental health diagnosis, 4) ever having been treated for substance use disorder, 5) bystander present when fatal overdose occurred, and 6) fatal drug use witnessed.

Frequencies and percentages of decedent demographics, overdose location,^¶¶¶ geographic region**** of the jurisdictions, and potential opportunities for intervention were stratified by opioid/stimulant involvement. Pairwise chi-squared testing was used to detect statistically significant differences (p<0.01) among percentages. Because of the potential for incomplete data, the analysis of potential opportunities for intervention only included deaths with overdose-specific circumstances noted in the medical examiner/coroner report (15,295; 94.2% of overdose deaths). Analyses were conducted using SAS statistical software (version 9.4; SAS Institute).

Results

Twenty-five jurisdictions reported 16,236 overdose deaths during January–June 2019. Among these, 7,936 (48.9%) involved opioids without stimulants, 5,301 (32.6%) involved opioids and stimulants, 2,056 (12.7%) involved stimulants without opioids, and 943 (5.8%) involved neither opioids nor stimulants (Table). In all regions, overdose deaths involving opioids without stimulants were most common (36.9%–54.1%), followed by deaths involving opioids and stimulants (30.6%–33.8%), then deaths involving stimulants without opioids (7.4%–27.1%) (Figure 1). This pattern was most prominent in Northeastern and Midwestern jurisdictions, where deaths involving opioids (with or without stimulants) accounted for 87.6% and 83.0%, respectively, of all overdose deaths.

More than two thirds (68.5%) of decedents were male, and three quarters (75.2%) were non-Hispanic White (Table). Among overdose deaths involving opioids (with and without stimulants), most decedents (53.3%) were aged 25–44 years; among overdose deaths involving stimulants without opioids, most decedents (55.7%) were aged 45–64 years. Evidence of injection drug use^†††† was more common among opioid-involved deaths than among deaths that did not involve opioids.

Most overdose deaths (83.8%) involved one or more of four illicit drugs (IMFs [61.5%], cocaine [28.3%], heroin [28.2%], or methamphetamine [17.6%]) (Table); nearly one half (49.8%) of these deaths involved two or more of those drugs. IMFs were involved in 80.4% of opioid overdose deaths with stimulants and in 72.2% without stimulants. Heroin was involved in 34.6% of opioid overdose deaths, and 73.6% of heroin overdose deaths co-involved IMFs (data not shown). Either cocaine or methamphetamine was involved in nearly all stimulant overdose deaths (96.2% with opioids, 97.5% without). Prescription opioids were involved more often in deaths involving opioids without stimulants (30.7%) than in those with stimulants (17.2%).

The 10 most frequently occurring opioid and stimulant combinations accounted for 76.9% of overdose deaths (Figure 2). Six drug combinations, including the three most common, involved IMFs and 1) no other opioid or stimulant (19.8% of deaths), 2) cocaine (10.5%), 3) heroin (10.3%), 4) heroin and cocaine (5.1%), 5) methamphetamine (3.7%), and 6) prescription opioids (3.3%). Deaths without IMFs involved a single opioid without other opioids or stimulants (only prescription opioids [9.2%], only heroin [3.2%]) or a single stimulant without other opioids or stimulants (only methamphetamine [6.3%], only cocaine [5.5%]).

More than three in five overdose deaths (62.7%) had evidence of at least one potential opportunity for intervention (Figure 3). Approximately one in ten opioid overdose deaths had evidence of past-month institutional release (10.7% with stimulants; 10.8% without stimulants) or previous overdose (10.9%; 12.1%). Mental health diagnoses were documented for one quarter (25.8%) of overdose deaths. Evidence of current or past substance use disorder treatment was more common among opioid overdose deaths (18.6% with stimulants; 19.1% without stimulants) than nonopioid overdose deaths (<10%). Among overdose deaths, 37% occurred with a bystander present.

Discussion

This report provides three critical insights that can inform overdose prevention efforts. First, approximately 80% of overdose deaths involved opioids, and three of four opioid overdose deaths involved IMFs. The supply of IMFs and overdose deaths involving synthetic opioids excluding methadone (primarily IMFs) are projected to have increased for the seventh straight year in 2019 (1).^§§§§ Second, IMFs, heroin, cocaine, or methamphetamine (alone or in combination) were involved in nearly 85% of overdose deaths. Complicating intervention and treatment efforts, one half of these deaths involved two or more of these four drugs. Third, potential opportunities for intervention, which could be targeted for overdose prevention, were documented in approximately 60% of overdose deaths.

Interventions should address characteristics of overdoses involving IMFs. First, IMFs can be highly potent (e.g., fentanyl has 50–100 times the potency of morphine; carfentanil has 30–100 times the potency of fentanyl) (13), and use might quickly progress to overdose (5,14), especially when injected. Consequently, improving overdose response time by expanding community naloxone distribution, increasing naloxone prescribing and dispensing from pharmacies, and encouraging persons to not use drugs when alone might reduce IMF overdose deaths (5,12). Second, powdered IMFs are often sold as or mixed with white powdered heroin (primarily east of the Mississippi River) with or without the knowledge of the person buying the products, but deaths involving IMFs and products containing IMFs are less prevalent in western black tar heroin markets.^¶¶¶¶ Mixing of IMFs into heroin, and in some places IMFs supplanting the heroin supply, is increasing over time, consistent with findings that more than seven in 10 (73.6%) heroin-involved overdose deaths co-involved IMFs. Pressing IMFs into counterfeit prescription pills resembling both prescription opioids and other drugs (e.g., benzodiazepines) has allowed IMFs to spread into additional drug markets. IMFs are difficult to mix consistently, resulting in possibly varying concentrations of IMFs between and within products, or persons might use IMFs when expecting to use heroin, other opioids, or (rarely) nonopioids; either could increase the risk for overdose.***** Interventions conducted by risk reduction organizations (e.g., syringe services programs) to reduce overdoses among persons exposed to IMFs (e.g., naloxone distribution) and to link populations at high risk (e.g., persons who inject drugs) with prevention and treatment services might mitigate these overdose risks (15).^{†††††} Finally, timely response by public health and public safety officials to growing threats such as mixing of IMFs in nonopioid products, and outbreaks involving fentanyl analogs (e.g., carfentanil) is warranted.^§§§§§

In this report, one third (32.6%) of overdose deaths co-involved opioids and stimulants. Co-use of opioids and stimulants elevates fatal overdose risk and is associated with poorer medical, mental health, and substance use disorder treatment outcomes (16). Supporting increased access to medications for opioid use disorder^¶¶¶¶¶ and evidence-based treatments for stimulant use disorders (17) can help mitigate risks. Research into more effective treatments for co-occurring opioid and stimulant use disorder is also needed. Methamphetamine was involved in approximately one half of stimulant overdose deaths without opioids. The methamphetamine supply has increased substantially since 2011,****** with accompanying increases in methamphetamine-related treatment admissions (18) and overdose deaths involving psychostimulants with abuse potential (e.g., methamphetamine) (1,4). Tracking of and response to these increases might help prevent further deaths.

Public health interventions targeting overdose risk factors identified in this report have shown effectiveness, especially for opioid overdose prevention (7). Recent release from an institution and previous overdose were both reported for approximately one in 10 opioid overdose deaths. Initiating or continuing medications for opioid use disorder among persons leaving prison (7,10) and expanding linkage to care programs targeting persons treated for a nonfatal overdose (7,9) can mitigate overdose risk. Also, outreach to groups at higher risk for overdose (e.g., persons who inject drugs) shows promise in reducing drug overdose deaths (7,15). For one quarter of deaths, there was evidence of a mental health diagnosis. Integrating substance use disorder and mental health treatment can improve treatment outcomes, which could help reduce drug overdoses (11,19). Finally, presence of a bystander at nearly four in 10 opioid- and stimulant-involved overdose deaths suggests a need to increase bystander naloxone training, access, and use (5,12). CDC, through the Overdose Data to Action program, is supporting expansions of programs linking persons at risk for overdose to treatment and risk reduction programs.

The findings in this report are subject to at least five limitations. First, the 25 jurisdictions are not nationally representative, and four states reported a subset of overdose deaths. Western states are underrepresented, likely resulting in an underestimation of methamphetamine overdose deaths that more frequently occur in the West (20). Second, toxicology testing and drug involvement determination varies over time and across jurisdictions. Third, all drugs detected are listed as involved when the cause of death does not specify drugs (e.g., multitoxicity death), which might overestimate drug involvement. Testing, drug involvement determination, and coding biases are minimized by focusing on commonly tested drugs frequently involved in deaths. Fourth, medical examiner/coroner reports likely underestimate intervention opportunities as investigators might have limited information. Finally, details about potential opportunities for intervention were limited (e.g., no information about whether a decedent was referred to treatment after a prior overdose), and they should therefore not necessarily be interpreted as missed opportunities.

Drug overdose interventions should address the combination and lethality of drugs being used (e.g., IMFs in combination with stimulants) and also work to prevent initiation of prescription drug misuse (e.g., inappropriate prescribing) and illicit drug use. The finding of this report that nearly 85% of overdose deaths involved IMFs, heroin, cocaine, or methamphetamine reflects rapid and continuing increases in the supply of IMFs and methamphetamine, coupled with illicit co-use of opioids and stimulants. This report also highlights important intervention opportunities for persons who use illicit drugs (especially IMFs), including the presence of bystanders, recent release from institutions, and high-risk routes of drug use (e.g., injection) that can be targeted to both prevent overdoses (e.g., by enhancing linkage to evidence-based treatment and risk reduction services) and improve response to overdoses to prevent deaths.