Prescribed Dosage Associated With Opioid-Related Deaths

Among patients prescribed opioids for chronic pain, those who died of an unintentional opioid overdose had been prescribed higher dosages on average than those who did not, according to a new study.

“Specifically, we found that the average prescribed daily dose was 98 morphine-equivalent milligrams (MEM) among those who died and 48 in the comparison group,” said lead study author Amy S.B. Bohnert, PhD, MHS, of the department of psychiatry, University of Michigan Medical School, and the VA Center for Clinical Management Research, Ann Arbor. “Although our group and others have found this association before, the methods we used in this paper were novel in allowing us to look at the dosage levels in a detailed way.”
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In this nested case-control study with risk-set sampling of controls, the researchers identified cases (opioid overdose decedents) and controls from a population of patients of the Veterans Health Administration prescribed opioids with a chronic pain diagnosis. They measured unintentional fatal opioid analgesic overdose from National Death Index records and prescribed opioid dosage from pharmacy records.

The investigators found the average prescribed opioid dosage was higher (P < 0.001) for cases (mean=98.1 MEM, SD=112.7; median=60, interquartile range, 30-120) than controls (mean=47.7 MEM, SD=65.2; median=25, interquartile range, 15-45). In a receiver operating characteristic analysis, they saw dosage as a moderately good “predictor” of opioid overdose death, indicating that, on average, overdose cases had a prescribed opioid dosage higher than 71% of controls.

“I was surprised how substantial the difference in opioid dosage was between those patients who died of an overdose and those who did not, given that our research methods involved matching,” Bohnert said. “Consequently, our comparison group was the same as the group who died of an overdose on factors like comorbid mental health problems and use of other medications.”

Depending on the health system, as much as 70% of the total quantity of opioids prescribed is dispensed to the patients with the 5% highest daily dosages, she said. “Although this is beyond the scope of what we were able to study directly, I think caution in prescribing high dosages is not only about protecting the patient but also protecting the broader community and addressing the public health problem of opioid misuse and overdose.”

For future research, Bohnert plans to study how often patients prescribed high dosages of opioids are tapered to lowered dosages or stopped completely and whether tapering changes risk for overdose, as well as other outcomes.

-Mike Bederka

Reference:

Bohnert AS, Logan JE, Ganoczy D, Dowell D. A detailed exploration into the association of prescribed opioid dosage and overdose deaths among patients with chronic pain. Med Care. Published online January 22, 2016.