A Large-Scale Observational Study on the Temporal Trends and Risk Factors of Opioid Overdose: Real-World Evidence for Better Opioids.

Background: The USA is in the midst of an opioid overdose epidemic. To address the epidemic, we conducted a large-scale population study on opioid overdose.

Objectives: The primary objective of this study was to evaluate the temporal trends and risk factors of inpatient opioid overdose. Based on its patterns, the secondary objective was to examine the innate properties of opioid analgesics underlying reduced overdose effects.

Methods: A retrospective cross-sectional study was conducted based on a large-scale inpatient electronic health records database, Cerner Health Facts, with (1) inclusion criteria for participants as patients admitted between 1 January, 2009 and 31 December, 2017 and (2) measurements as opioid overdose prevalence by year, demographics, and prescription opioid exposures.

Results: A total of 4,720,041 patients with 7,339,480 inpatient encounters were retrieved from Cerner Health Facts. Among them, 30.2% patients were aged 65+ years, 57.0% female, 70.1% Caucasian, 42.3% single, 32.0% from the South, and 80.8% in an urban area. From 2009 to 2017, annual opioid overdose prevalence per 1000 patients significantly increased from 3.7 to 11.9 with an adjusted odds ratio (aOR): 1.16, 95% confidence interval (CI) 1.15-1.16. Compared to the major demographic counterparts, being in (1) age group: 41-50 years (overall aOR 1.36, 95% CI 1.31-1.40) or 51-64 years (overall aOR 1.35, 95% CI 1.32-1.39), (2) marital status: divorced (overall aOR 1.19, 95% CI 1.15-1.23), and (3) census region: West (overall aOR 1.32, 95% CI 1.28-1.36) were significantly associated with a higher odds of opioid overdose. Prescription opioid exposures were also associated with an increased odds of opioid overdose, such as meperidine (overall aOR 1.09, 95% CI 1.06-1.13) and tramadol (overall aOR 2.20, 95% CI 2.14-2.27). Examination on the relationships between opioid analgesic properties and their association strengths, aORs, and opioid overdose showed that lower aOR values were significantly associated with (1) high molecular weight, (2) non-interaction with multi-drug resistance protein 1 or interaction with cytochrome P450 3A4, and (3) non-interaction with the delta opioid receptor or kappa opioid receptor.

Conclusions: The significant increasing trends of opioid overdose at the inpatient care setting from 2009 to 2017 suggested an ongoing need for efforts to combat the opioid overdose epidemic in the USA. Risk factors associated with opioid overdose included patient demographics and prescription opioid exposures. Moreover, there are physicochemical, pharmacokinetic, and pharmacodynamic properties underlying reduced overdose effects, which can be utilized to develop better opioids.