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Higher opioid dosage linked to overdose deaths in patients with chronic pain

Reducing the recommended opioid dosage threshold for chronic pain below the 100 morphine-equivalent mg currently used in recent guidelines could potentially benefit many patients who are at risk for overdose, according to data published in Medical Care.

“In recent years, the public health problem of prescription opioid overdose (also called ‘poisoning’) emerged when opioid prescribing and usage increased in response to changes in treatment practices for chronic, noncancer pain,” Amy S.B. Bohnert, PhD, MHS, of the University of Michigan Medical School, department of psychiatry, and colleagues wrote. “Evidence indicated that many opioid overdose victims were prescribed opioids before their deaths. Given the concurrent trends in overdose deaths and increased prescribing for chronic pain, the safety of long-term opioid prescribing for chronic, noncancer pain in particular has been increasingly scrutinized.”

To analyze the link between opioid dosages as a continuous measure in connection with the risk for unintentional overdose death, as well as to determine the range of dosages associated with overdose death, the researchers conducted a nested case-control study with patients selected through the Veterans Health Administration (VHA), from Oct. 1, 2003 to Sept. 30, 2009. Both the case group, made up of patients who had suffered an unintentional overdose death, and the control group included 221 patients who had been diagnosed with chronic pain and prescribed opioids.

Data on unintentional overdose deaths were collected from the National Death Index, obtained by the VHA Office of Mental Health Operations. Patients in the control group were selected from a random sample registry created by the VA Serious Mental Illness Treatment Resource and Evaluation Center.

According to the researchers, opioid dosages were higher among cases of unintentional overdose death, with a mean dosage of 98.1 morphine-equivalent mg (MEM), than in the control group, in which the mean dosage was 47.7 MEM. Median doses also indicated higher levels among cases of unintentional overdose deaths, with 60 MEM (interquartile range, 30-120 MEM) compared with a median of 25 MEM (interquartile range, 15-45 MEM) in the control group. In addition, the researchers, in an receiver operating characteristic analysis, based on a logistic regression model predicting case status, determined that opioid dosage was a good “predictor” of overdose death, with overdose cases having a higher dosage than 71% of patients in the control group (95% CI, 0.66-0.76).

“A clear [dosage] cutpoint to distinguish between overdose cases and controls was not found,” Bohnert and colleagues wrote. “However, a 100 MEM dosage threshold has been used in many recent opioid prescribing guidelines based on earlier studies that used this level to define the highest dosage category, and these data suggest that even lower recommended dosage thresholds would affect proportionately few patients not at risk for overdose while potentially benefitting many patients who are at risk.” – by Jason Laday

Disclosure: The authors report no relevant financial disclosures.