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Escalating Opioid Dose Is Associated With Mortality

A Comparison of Patients With and Without Opioid Use Disorder

Hser, Yih-Ing, PhD; Saxon, Andrew J., MD; Mooney, Larissa J., MD; Miotto, Karen, MD; Zhu, Yuhui, MS; Yoo, Caroline K., MPH; Liang, Di, PhD; Huang, David, DrPh; Bell, Douglas S., MD, PhD

doi: 10.1097/ADM.0000000000000458
Original Research

Objective: Prescription Drug Monitoring Programs (PDMPs) are intended to help reduce prescription drug misuse and opioid overdose, yet little is known about the longitudinal patterns of opioid prescribing that may be associated with mortality. This study investigated longitudinal opioid prescribing patterns among patients with opioid use disorder (OUD) and without OUD in relation to mortality using PDMP data.

Methods: Growth modeling was used to examine opioid prescription data from the California PDMP for a 4-year period before death or a comparable period ending in 2014 for those remaining from a sample of 7728 patients (2576 with OUD, and 5152 matched non-OUD controls) treated in a large healthcare system.

Results: Compared to controls, individuals with OUD (alive and deceased) had received significantly more opioid prescriptions, greater number of days’ supply, and steeper increases of opioid dosages over time. For morphine equivalents (ME, in grams), the interaction of OUD and mortality was significant at both intercept (β = 10.4, SE = 4.4, P < 0.05) and slope (β = 6.0, SE = 1.1, P < 0.001); deceased OUD patients demonstrated the sharpest increase (ie, an average yearly increment of 7.84 grams over alive patients without OUD) and ended with the highest level of opioids prescribed before they died (ie, 20.2 grams higher). Older age, public health insurance, cancer, and chronic pain were associated with higher number and dose of opioid prescriptions.

Conclusions: Besides the amount of prescriptions, clinicians must be alert to patterns of opioid prescription such as escalating dosage as critical warning signals for heightened mortality risks, particularly among patients with OUD.

University of California, Los Angeles, CA (YIH, LJM, KM, YZ, CKY, DH, DSB); Veterans Affairs Puget Sound Health Care System, Seattle, WA (AJS); University of California, San Diego, CA (DL).

Send correspondence to Yih-Ing Hser, PhD, UCLA Integrated Substance Abuse Programs, 11075 Santa Monica Blvd, Suite 200, Los Angeles, CA 90025. E-mail:

Received 3 July, 2018

Accepted 3 September, 2018

This project has been funded in part with federal funds from the National Institute on Drug Abuse (NIDA), National Institutes of Health, Department of Health and Human Services, under contract HHSN271201400028C. Additional funding was provided by the National Center for Advancing Translational Science (NCATS) through grant number UL1TR001881 to the UCLA CTSI.

The authors disclosing relevant financial interests, activities, relationships, and affiliations are as follows: Andrew J. Saxon: receives royalties as a section editor for UpToDate.

All the other authors report no financial or other possible conflicts of interest.

© 2019 American Society of Addiction Medicine