Escalating Opioid Dose Is Associated With Mortality: A Comparison of Patients With and Without Opioid Use Disorder

Abstract

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 over a 4-year period prior to death or a comparable period ending in 2014 for those remaining from a sample of 7,728 patients (2,576 with OUD, and 5,152 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<.05) and slope (β=6.0, SE=1.1, p<.001); deceased OUD patients demonstrated the sharpest increase (i.e., 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 (i.e., 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.

Deep proteomics and phosphoproteomics reveal novel biological pathways perturbed by morphine, morphine‐3‐glucuronide and morphine‐6‐glucuronide in human astrocytes

“…The opioid epidemic, caused by over-prescription, continues to increase numbers of patients addicted to opioids, as well as users transitioning to heroin and other drugs (Blanco & Volkow, 2019). It is estimated that more than hundred deaths every day in the United States are caused by misuse or opioid overdose (Hser et al, 2019). Although it is generally assumed that physiological homeostatic adaptations cause these side effects, little is known about their underlying molecular and cellular mechanisms.Inside the body, morphine is metabolized into the two main active metabolites morphine-3-glucuronide (M3G) and morphine-6glucuronide (M6G).…”

Impact of opioid dose escalation on the development of substance use disorders, accidents, self‐inflicted injuries, opioid overdoses and alcohol and non‐opioid drug‐related overdoses: a retrospective cohort study

“…The Canadian study also found that men were also more likely to die of opioid‐related causes . Other US studies found an increased risk of opioid misuse and mortality with dose escalation . Other outcomes potentially related to opioid dose escalation, such as car accidents, self‐inflicted injuries and other drug‐related overdoses, have not been evaluated.…”

Relationship Between Cardiovascular Disease Pathology and Fatal Opioid and Other Sedative Overdose: A Post-Mortem Investigation and Pilot Study

“…A retrospective cohort study concluded that the leading causes of death related to opioid use are overdose, cardiovascular disease (CVD), cancer, and infectious diseases (Hser et al, 2019). Other studies have linked adverse cardiovascular effects such as coronary heart disease (CHD) (Khodneva et al, 2016), arrhythmia (Doshi et al, 2019a), cardiac arrest (Morrow et al, 2019), and ischemic events (Doshi et al, 2019b) with prescribed opioids and/or opioid overdose.…”