(105) Characteristics Associated with Overdose after Opioid Prescription to Younger Individuals

Background & Introduction: Adolescents and young adults are experiencing increases in opioid overdose-related deaths. From 1999 to 2016, opioid-related mortality among individuals aged 13 to 25 years increased 268.2% (1). Then, in the setting of the COVID-19 pandemic, in the one year between 2019 and 2020 drug overdose deaths among individuals ages 15-34 increased by 36.5% (2). Part of the reason for this trend in mortality is the presence of illicitly manufactured fentanyl in the non-prescribed drug supply. Overdose deaths of adolescents (aged 14-18 years) involving fentanyl increased from 1.21 per 100,000 population in 2019 to 4.23 per 100,000 population in 2021, a 3.5x increase (3). Although fentanyl is a driver of mortality, prescription opioids remain a risk for adolescents. Recreational misuse of opioids follows a different profile when compared with adults, as teenagers may be more likely to experiment with prescription opioids (4). It is therefore still of importance that prescriptions of opioids to adolescents be done with careful consideration. The goal of this study is to determine the risk of prescribing opioids to formerly opioid-naïve children, adolescents and young adults by analyzing a comprehensive public health dataset from Oregon.

Methods: This was a retrospective study of the Oregon Comprehensive Opioid Risk Registry (CORR) dataset, which combines the voluntary Oregon All Payer Claims Database (APCD) with the Oregon PDMP, Oregon vital records death certificates, the Oregon hospital discharge database, emergency medical services (EMS), and ED discharges (5). Individuals aged 2-24 as of January 1, 2016, and who had 1 or more opioid prescriptions filled between January 1, 2016, and December 31, 2019 were included. We selected each patient's first opioid prescription in this period as their index prescription. Patient age was categorized into age bands (2-11, 12-17, 18-24 years). Comorbid conditions were identified using Elixhauser comorbidity measures and categorized into 0 or ≥1. Key characteristics of the index prescription, such as the opioid type, duration of action (long or short-acting), days’ supply, and morphine milligram equivalents (MMEs) of the prescription were computed. The main outcome was an incident non-fatal or fatal overdose at 12 months following the index prescription. Logistic regression models were used to calculate the odds ratios of patient and prescription level risk factors with respect to opioid overdose. This cohort study received IRB approval from the Mass General Brigham Human Research Committee.

Results: There were 117,693 patients who met inclusion criteria, 7.7% (n=9,002) aged 2-11 years, 30.4% (n=35,577) aged 12-17 years, and 61.9% (n=72,467) aged 18-24 years. Most patients were female (n=64,929, 55.5%). Insurance was 50.0% (n=58,470) commercial and 49.7% (n=58,137) Medicaid. There were 45,696 (38.8%) patients with ≥1 Elixhauser comorbidity coded, and 4,643 (3.9%) patients with a substance use disorder coded. Index prescriptions included: hydrocodone short-acting (n=72,503, 61.9%), oxycodone short-acting (n=32,495, 27.8%), codeine (n=7,197, 6.2%), and tramadol (n=4,141, 3.5%). Long-acting formulations were rarely prescribed (n=101, 0.1%). Most prescriptions were for fewer than 7 days’ duration (n=107,043, 91.5%).

There were 92 overdoses within 12 months of index prescription, which is 0.08%. There were no overdoses in the 2-11 year-old cohort, 20 in the 12-17 year-old cohort, and 72 in the 18-24 year-old cohort. In the multivariable analysis, only three variables were associated with differences in risk of overdose. Patients with ≥1 comorbidity were more at risk (adjusted odds ratio (aOR) 2.90 (95% confidence interval (CI) 1.76-4.77)), as were those with a history of substance use disorder (aOR 5.49 (95% CI 3.32-9.09)). Index prescriptions with MMEs >= 75 mg were protective (aOR 0.49 (95% CI 0.31-0.78)). Non-significant patient characteristics included: age (aOR 1.51 (95% CI 0.91-2.50) for patients aged 18-24 years vs. 12-17 years); sex (aOR 1.37 (95% CI 0.90-2.07) for males vs. females); and payer (aOR 1.25 (95% CI 0.90-2.07) for Medicaid vs. other). Likewise, there were no detectable differences in index prescription opioid type when compared to hydrocodone short-acting: codeine (aOR 0.68 (95% CI 0.25-1.90), oxycodone short-acting (aOR 1.49 (95% CI 0.90-2.47)), or tramadol (aOR 1.02 (95% CI 0.37-2.83)). Risk associated with an index long-acting prescription, compared with short-acting prescription, did not reach statistical significance (aOR 3.07 (95% CI 0.30-31.63).

Conclusion & Discussion: Opioid overdose after initial prescription of opioids to younger patients is rare in Oregon (0.08%). Certain patients appear to be more at risk, including those with medical comorbidities or a history of substance use disorder. There were no detectable differences in subsequent overdose based upon which opioid was prescribed, including long-acting vs. short-acting opioids, and prescriptions for MME > 75 mg were less associated with overdose; these findings may be the consequence of a low number of primary outcomes. Studies involving younger individuals in states where opioid overdose occurs more frequently or on a national level may elucidate other risk factors. An initial opioid prescription to younger individuals should still be done with caution, and educating about the risk of fentanyl, including in illicitly manufactured pills, is paramount in this population.

References: 1. Gaither, J. R., Shabanova, V., & Leventhal, J. M. (2018). US National Trends in Pediatric Deaths From Prescription and Illicit Opioids, 1999-2016. JAMA network open, 1(8), e186558. https://doi.org/10.1001/jamanetworkopen.2018.6558

2. Lee, H., & Singh, G. K. (2022). Monthly Trends in Drug Overdose Mortality among Youth Aged 15-34 Years in the United States, 2018-2021: Measuring the Impact of the COVID-19 Pandemic. International journal of MCH and AIDS, 11(2), e583. https://doi.org/10.21106/ijma.583

3. Friedman, J., Godvin, M., Shover, C. L., Gone, J. P., Hansen, H., & Schriger, D. L. (2022). Trends in Drug Overdose Deaths Among US Adolescents, January 2010 to June 2021. JAMA, 327(14), 1398–1400. https://doi.org/10.1001/jama.2022.2847

4. Sandelich, S., Hooley, G., Hsu, G., Rose, E., Ruttan, T., Schwarz, E. S., Simon, E., Sulton, C., Wall, J., & Dietrich, A. M. (2024). Acute opioid overdose in pediatric patients. Journal of the American College of Emergency Physicians open, 5(2), e13134. https://doi.org/10.1002/emp2.13134

5. Hallvik, S. E., Dameshghi, N., El Ibrahimi, S., Hendricks, M. A., Hildebran, C., Bishop, C. J., & Weiner, S. G. (2021). Linkage of public health and all payer claims data for population-level opioid research. Pharmacoepidemiology and drug safety, 30(7), 927–933. https://doi.org/10.1002/pds.5259