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. 2018 May 1;319(17):1819–1821. doi: 10.1001/jama.2018.2844

Changes in Synthetic Opioid Involvement in Drug Overdose Deaths in the United States, 2010-2016

Christopher M Jones 1,, Emily B Einstein 2, Wilson M Compton 2
PMCID: PMC6583033  PMID: 29715347

Abstract

This study uses National Vital Statistics System data to describe trends in synthetic opioid involvement in drug overdose deaths in the United States from 2010 to 2016.


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).

Table. Synthetic Opioid Involvement in Overdose Deathsa Involving Illicit and Psychotherapeutic Drugs in the United States, 2010-2016.

Drug Class 2010 2011 2012 2013 2014 2015 2016 P Value for Trendb
Total Overdose Deaths, No. Deaths Involving Synthetic Opioids, No. (%) Total Overdose Deaths, No. Deaths Involving Synthetic Opioids, No. (%) Total Overdose Deaths, No. Deaths Involving Synthetic Opioids, No. (%) Total Overdose Deaths, No. Deaths Involving Synthetic Opioids, No. (%) Total Overdose Deaths, No. Deaths Involving Synthetic Opioids, No. (%) Total Overdose Deaths, No. Deaths Involving Synthetic Opioids, No. (%) Total Overdose Deaths, No. Deaths Involving Synthetic Opioids,
No. (%)
Drug overdose deaths 38 329 3007 (7.8) 41 340 2666 (6.4) 41 502 2628 (6.3) 43 982 3105 (7.1) 47 055 5544 (11.8) 52 404 9580 (18.3) 63 632 19 413 (30.5) <.01
Synthetic opioidsc 3007 788 (26.2) 2666 729 (27.3) 2628 822 (31.3) 3105 746 (24.0) 5544 1358 (24.5) 9580 2248 (23.5) 19 413 4414 (22.7) .03
Any opioid 21 089 3007 (14.3) 22 784 2666 (11.7) 23 166 2628 (11.3) 25 052 3105 (12.4) 28 647 5544 (19.4) 33 091 9580 (29.0) 42 249 19 413 (45.9) <.01
Prescription opioids 14 583 939 (6.4) 15 140 889 (5.9) 14 240 861 (6.0) 14 145 1015 (7.2) 14 838 1489 (10.0) 15 281 2263 (14.8) 17 087 4055 (23.7) <.01
Heroin 3036 45 (1.5) 4397 44 (1.0) 5925 69 (1.2) 8257 209 (2.5) 10 574 1027 (9.7) 12 989 2685 (20.7) 15 469 5781 (37.4) <.01
Cocaine 4183 167 (4.0) 4681 189 (4.0) 4404 182 (4.1) 4944 245 (5.0) 5415 628 (11.6) 6784 1542 (22.7) 10 375 4184 (40.3) <.01
Psychostimulants 1854 73 (3.9) 2266 93 (4.1) 2635 91 (3.5) 3627 142 (3.9) 4298 276 (6.4) 5716 494 (8.6) 7542 1042 (13.8) <.01
Benzodiazepines 6497 746 (11.5) 6872 665 (9.7) 6524 655 (10.0) 6973 804 (11.5) 7945 1222 (15.4) 8791 1801 (20.5) 10 684 3308 (31.0) <.01
Antidepressants 3889 568 (14.6) 4113 463 (11.3) 4259 464 (10.9) 4458 571 (12.8) 4768 723 (15.2) 4894 808 (16.5) 4812 1002 (20.8) .04
Antipsychotics and neuroleptics 1351 184 (13.6) 1321 131 (9.9) 1333 144 (10.8) 1474 172 (11.7) 1588 224 (14.1) 1665 282 (16.9) 1877 385 (20.5) .04
Barbiturates 296 33 (11.1) 315 28 (8.9) 323 34 (10.5) 335 38 (11.3) 320 33 (10.3) 404 56 (13.9) 409 88 (21.5) .02
Other illicit drugs 190 17 (8.9) 229 18 (7.9) 243 17 (7.0) 274 22 (8.0) 300 41 (13.7) 427 68 (15.9) 543 144 (26.5) <.01
a

Deaths are not mutually exclusive. Deaths involving >1 drug or drug class are counted multiple times.

b

Based on joinpoint regression analysis.

c

For the synthetic opioids category, the columns for “deaths involving synthetic opioids” represent deaths in which synthetic opioids were the only drug involved in the overdose.

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).

Figure. Percentage of Synthetic Opioid-Related Overdose Deaths Involving Illicit or Psychotherapeutic Drugs or Alcohol in the United States, 2016.

Figure.

aDeaths are not mutually exclusive. Percentages sum to more than 100%.

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.

References

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