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From 1999 to 2016, opioid-related mortality among adolescents and young adults aged 13 to 25 years (referred to as youth) increased 3-fold.1 Opioid overdose deaths in adult populations often involve other substances, particularly benzodiazepines and, increasingly, stimulants.2,3 Little is known about polysubstance involvement in opioid overdose deaths among youth. In this cross-sectional study, we examined national trends in polysubstance-involved opioid overdose deaths among youth in the US.
We used serial cross-sectional data from the US Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) Multiple Cause of Death file from January 1999 to December 2018.4 We identified deaths that involved opioids among youth with complete demographic information using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), codes X40-45, X60-65, X85, and Y10-15. Opioids were classified as synthetic opioids, including fentanyl (T40.4); heroin (T40.1); prescription opioids (T40.2-40.3); and other opioids, including opium (T40.0) and other/unspecified narcotics (T40.6). Methadone was classified as a prescription opioid.1,5 This research was not considered human subjects research by the Boston University Medical Campus Institutional Review Board and did not require ethical review and informed consent procedures.
We extracted total opioid overdose deaths and those involving other substances, including benzodiazepines (T42.2), alcohol (T51.0-51.9), antidepressants (T43.0-T43.2), cannabis (T40.7), antipsychotics/neuroleptics (T43.3-T43.5), barbiturates (T42.3), cocaine (T40.5), and psychostimulants other than cocaine (T43.6). We created a category for any stimulant combining cocaine and other psychostimulants. We calculated overdose deaths involving only opioids as total opioid overdose deaths minus opioid overdose deaths involving 1 or more other substance.
We used descriptive statistics with 2-tailed χ2 tests to characterize deaths by age, sex, race/ethnicity, substances involved, and census region. Significance was set at P < .05 Analyses were performed using Stata version 15.1 (StataCorp).
Between 1999 and 2018, opioid-only and polysubstance-involved overdose deaths among youth increased by 384% and 760%, respectively. In 2018, polysubstance-involved opioid overdose deaths became more prevalent than those involving only opioids (polysubstance: 0.22 deaths per 100 000 individuals; 95% CI, 0.21-0.23; opioids only: 0.19 deaths per 100 000 individuals; 95% CI, 0.18-0.20) (Figure, A). From 2010 to 2018, opioid overdose deaths involving stimulants increased 351%, surpassing those involving benzodiazepines (stimulants: 0.14 deaths per 100 000 individuals; 95% CI, 0.13-0.15; benzodiazepines: 0.09 deaths per 100 000 individuals; 95% CI, 0.08-0.09) (Figure, B). Overall overdose deaths declined between 2017 and 2018 (2017: 0.46 deaths per 100 000 individuals; 95% CI, 0.45-0.48; 2018: 0.41 deaths per 100 000 individuals; 95% CI, 0.40-0.43).
A, Trends in opioid overdose mortality with and without other substances among adolescents and young adults aged 13 to 25 years in the US from 1999 to 2018. B, Trends in substance involvement in opioid overdose deaths among young people aged 13 to 25 years in the US from 1999-2018.
In 2018, there were 4623 opioid overdose deaths among youth (Table). Synthetic opioids were most commonly involved (3387 [73.3%]). More than half of all deaths (2476 [53.6%]) involved 1 or more other substance. Stimulants were involved in 1541 of 2476 polysubstance-involved opioid overdose deaths (62.2%) and 1541 of 4623 total opioid overdose deaths (33.3%). By 2018, cocaine was the substance most commonly involved in overdose deaths involving other substances (989 of 2476 [39.9%]).
To our knowledge, this is the first study characterizing polysubstance involvement in opioid overdose deaths among youth. For the first time, in 2018, polysubstance-involved opioid overdose deaths became more prevalent than deaths involving opioids alone. Of the polysubstance-involved opioid overdose deaths, stimulants were most commonly involved.
Our results are consistent with data from the general adult population, which shows stimulant-involved opioid overdose deaths increasing over the past decade.3 Moreover, our study is consistent with data demonstrating that cocaine is now the substance most commonly coinvolved in opioid overdose deaths.5
Limitations of this study include potential death misclassification, inaccurate identification of substances, and nonspecific reporting on death certificates causing undercounts of specific drug classes. The CDC WONDER data set is unable to stratify further deaths from psychostimulants other than cocaine, a category that includes methamphetamine and prescribed stimulants. Future studies should further delineate the age-related and geographic differences in polysubstance overdoses over time.6
These results underscore the evolving heterogeneity of the overdose epidemic among youth. Treatment and harm reduction models for opioid use disorders among youth must recognize and address the co-occurrence of other substance use disorders.
Accepted for Publication: April 28, 2020.
Published Online: November 23, 2020. doi:10.1001/jamapediatrics.2020.5035
Corresponding Author: Jamie K. Lim, MD, Department of Pediatrics, Boston Medical Center, 850 Harrison Ave, Boston, MA 02118 (email@example.com).
Author Contributions: Mr Earlywine and Dr Hadland had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Lim, Earlywine, Bagley, Hadland.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Lim.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Earlywine.
Obtained funding: Hadland.
Administrative, technical, or material support: Earlywine.
Supervision: Marshall, Hadland.
Conflict of Interest Disclosures: None reported.
Funding/Support: Dr Bagley was supported by grant 1K23DA044324-01 from the National Institute on Drug Abuse. Dr Marshall was supported by grant P20-GM125507 from the National Institute of General Medical Sciences. Dr Hadland was supported by grants NIH/NIDA K23DA045085 and L40DA042434 from the National Institute on Drug Abuse and by a Thrasher Early Career Award.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Lim JK, Earlywine JJ, Bagley SM, Marshall BDL, Hadland SE. Polysubstance Involvement in Opioid Overdose Deaths in Adolescents and Young Adults, 1999-2018. JAMA Pediatr. 2021;175(2):194–196. doi:10.1001/jamapediatrics.2020.5035
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