Drug overdose deaths are at unprecedented levels in the United States.1 Prescription opioids have been the most common drug involved in overdose deaths, but heroin and synthetic opioids (primarily illicit fentanyl) are increasingly implicated in overdoses.2 In addition, synthetic opioids are increasingly found in illicit drug supplies of heroin, cocaine, methamphetamine, and counterfeit pills.3 To date, the involvement of synthetic opioids in overdose deaths involving other drugs is not well characterized, limiting the ability to implement effective clinical and public health strategies. Using 2010-2016 mortality data, we describe recent trends for synthetic opioid involvement in drug overdose deaths.

Methods

This research was exempt from institutional review board review by regulation. Data are from the National Vital Statistics System multiple cause of death file, based on death certificates submitted by medical examiners and coroners1 and including information on all deaths in the United States. Drug overdose deaths were those assigned an underlying cause of death using the International Classification of Diseases, Tenth Revision (ICD-10) codes (X40-X44 [unintentional], X60-X64 [suicide], X85 [homicide], and Y10-Y14 [undetermined intent]). Among drug overdose deaths, opioid-related deaths were those assigned ICD-10 codes T40.0 to T40.4, and T40.6. Prescription opioids were defined as natural/semi-synthetic opioids (T40.2) and methadone (T40.3); heroin (T40.1); synthetic opioids excluding methadone (T40.4); cocaine (T40.5); psychostimulants with abuse potential (T43.6); benzodiazepines (T42.4); antidepressants (T43.0-T43.2); antipsychotics and neuroleptics (T43.3-T43.5); barbiturates (T42.3); other illicit drugs (cannabis, lysergic acid diethylamide [LSD], and other hallucinogens, T40.7-T40.9); and alcohol (T51.0).

We calculated the number of synthetic opioid-involved overdose deaths by year for 2010 through 2016 overall and the number and percentage of overdose deaths involving the psychotherapeutic and illicit drugs listed above in which synthetic opioids were involved in the death. In addition, we calculated the number and percentage of synthetic opioid overdose deaths in 2016 also involving any drug or alcohol and psychotherapeutics, illicit drugs, or alcohol. The Joinpoint Regression Program (National Cancer Institute), version 4.3.1.0, was used to examine statistically significant changes in trends (eg, P trend) from 2010 through 2016. Because National Vital Statistics System data are not drawn from a sample but represent the full census of deaths in the United States, standard errors and CIs for estimates were not included. A 2-sided P value less than .05 was considered statistically significant.

Results

Among the 42 249 opioid-related overdose deaths in 2016, 19 413 involved synthetic opioids, 17 087 involved prescription opioids, and 15 469 involved heroin. Synthetic opioid involvement in these deaths increased significantly from 3007 (14.3% of opioid-related deaths) in 2010 to 19 413 (45.9%) in 2016 (P for trend <.01). Significant increases in synthetic opioid involvement in overdose deaths involving prescription opioids, heroin, and all other illicit or psychotherapeutic drugs were found from 2010 through 2016 (Table).

Among synthetic opioid–related overdose deaths in 2016, 79.7% involved another drug or alcohol. The most common co-involved substances were another opioid (47.9%), heroin (29.8%), cocaine (21.6%), prescription opioids (20.9%), benzodiazepines (17.0%), alcohol (11.1%), psychostimulants (5.4%), and antidepressants (5.2%) (Figure).

Discussion

In 2016, synthetic opioids eclipsed prescription opioids as the most common drug involved in overdose deaths in the United States. These findings underscore the rapidly increasing involvement of synthetic opioids in the drug overdose epidemic and in recent increases in overdose deaths involving illicit and psychotherapeutic drugs. This analysis was limited by the 15% to 25% of death certificates in which the type of drug(s) involved in the overdose was not specified, an omission due to lack of toxicological testing or failure to record test results on death certificates. Thus, the numbers reported are likely underestimates. In addition, some of the increase in synthetic opioid involvement found in this study may be related to increased testing and detection of synthetic opioids.

Lack of awareness about synthetic opioid potency, variability, availability, and increasing adulteration of the illicit drug supply poses substantial risks to individual and public health.4,5 Widespread public health messaging is needed, and clinicians, first responders, and lay persons likely to respond to an overdose should be trained on synthetic opioid risks and equipped with multiple doses of naloxone. These efforts should be part of a comprehensive strategy to reduce the illicit supply of opioids and expand access to medication-assisted treatment for opioid addiction.

Section Editor: Jody W. Zylke, MD, Deputy Editor.

Back to top Article Information

Accepted for Publication: February 26, 2018.

Corresponding Author: Christopher M. Jones, PharmD, MPH, Substance Abuse and Mental Health Services Administration, 5600 Fishers Ln, Ste 18E63, Rockville, MD 20857 (christopher.jones@samhsa.hhs.gov).

Author Contributions: Dr Jones had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Jones.

Critical revision of the manuscript for important intellectual content: Compton, Einstein.

Statistical analysis: Jones.

Supervision: Jones.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Compton reported owning stock in General Electric, 3M, and Pfizer. No other disclosures were reported.

Disclaimer: The findings and conclusions of this study are those of the authors and do not necessarily reflect the views of the Substance Abuse and Mental Health Services Administration or the National Institute on Drug Abuse of the National Institutes of Health.