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Invited Commentary
April 11, 2011

Limiting the Potential Harms of High-Dose Opioid TherapyComment on “Opioid Dose and Drug-Related Mortality in Patients With Nonmalignant Pain”

Author Affiliations

Author Affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.

Arch Intern Med. 2011;171(7):691-693. doi:10.1001/archinternmed.2011.101

Randomized trials provide the gold standard for testing the efficacy of pharmacological therapies. But to obtain reasonable estimates of risk for rare but serious events in the highly comorbid populations in which therapies are actually used, we need to turn to observational studies such as the article by Gomes et al concerning the experience of over 600 000 patients receiving opioids over a nearly 10-year period through the Ontario Provincial Drug Program. After adjustment for an array of clinical and demographic factors, the investigators found that average daily doses of opioids higher than 200 mg of morphine (or equivalent) were associated with nearly 3 times the risk of opioid-related mortality compared with doses lower than 20 mg. Their results are consistent with an those of earlier study by Dunn et al1 that reported a nearly 9 times greater risk of overdose in patients prescribed opioid doses higher than 100 mg of morphine or equivalent. By clearly linking mortality risk with prescribed dose, the articles by Gomes et al and Dunn et al1 both suggest that there are mortality risks inherent in high-dose opioid therapy. The initial study of opioid overdose mortality in West Virginia by Hall et al2 pointed to drug diversion and “doctor shopping” as important causes of opioid overdose. This study thus suggested that much of the overdose risk associated with opioids was due to bad behavior on the part of patients. It did not examine prescribed opioid dose as a risk factor.3

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