Background Opioid overdoses have contributed significantly to mortality in the United States. Despite long-standing recommendations from the Centers for Disease Control and Prevention to co-prescribe naloxone for patients receiving opioids who are at high risk of overdose, compliance with these guidelines has remained low. Objectives The objective of this study was to develop and evaluate a hospital-wide electronic health record (EHR)-based clinical decision support (CDS) tool designed to promote naloxone co-prescription for high-risk opioids. Methods We employed an iterative approach to develop a point-of-order, interruptive EHR alert as the primary intervention and assessed naloxone prescription rates, EHR efficiency metrics, and barriers to adoption. Data was obtained from our EHR's clinical data warehouse and analyzed using statistical process control and Chi-square analyses to assess statistically significant differences in prescribing rates during the intervention periods. Results The initial implementation phase of the intervention, spanning from April 2019 to May 2022, yielded a nearly 3-fold increase in the proportion of high-risk patients receiving naloxone, rising from 13.4% [95% CI, 12.9% - 13.8%] to 36.4% [95% CI, 35.2% - 37.5%; p = 1 x 10-38]. Enhancements to the CDS design and logic during the subsequent iteration's study period, June 2022 and December 2023, reduced the number of CDS triggers by more than 30-fold while simultaneously driving an additional increase in naloxone receipt to 42.7% [95% CI, 40.6% - 44.8%; p = 2 x 10-5]. The efficiency of the CDS demonstrated marked improvement, with prescribers accepting the naloxone co-prescription recommendation provided by the CDS in 41.1% of the encounters in version two, compared to 6.2% in version one (p = 6 x 10-9). Conclusion This study offers a sustainable and scalable model to address low rates of naloxone co-prescription and may also be used to target other opportunities for improving guideline-concordant prescribing practices.
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