Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths

Context The rate of prescription opioid-related overdose death increased substantially in the United States over the past decade. Patterns of opioid prescribing may be related to risk of overdose mortality. Objective To examine the association of maximum prescribed daily opioid dose and dosing schedule ("as needed," regularly scheduled, or both) with risk of opioid overdose death among patients with cancer, chronic pain, acute pain, and substance use disorders. Design Case-cohort study. Setting Veterans Health Administration (VHA), 2004 through 2008. Participants All unintentional prescription opioid overdose decedents (n=750) and a random sample of patients (n=154 684) among those individuals who used medical services in 2004 or 2005 and received opioid therapy for pain. Main Outcome Measure Associations of opioid regimens (dose and schedule) with death by unintentional prescription opioid overdose in subgroups defined by clinical diagnoses, adjusting for age group, sex, race, ethnicity, and comorbid conditions. Results The frequency of fatal overdose over the study period among individuals treated with opioids was estimated to be 0.04%. The risk of overdose death was directly related to the maximum prescribed daily dose of opioid medication. The adjusted hazard ratios (HRs) associated with a maximum prescribed dose of 100 mg/d or more, compared with the dose category 1 mg/d to less than 20 mg/d, were as follows: among those with substance use disorders, adjusted HR=4.54 (95% confidence interval [CI], 2.46-8.37; absolute risk difference approximation [ARDA]=0.14%); among those with chronic pain, adjusted HR=7.18 (95% CI, 4.85-10.65; ARDA=0.25%); among those with acute pain, adjusted HR=6.64 (95% CI, 3.31-13.31; ARDA=0.23%); and among those with cancer, adjusted HR=11.99 (95% CI, 4.42-32.56; ARDA=0.45%). Receiving both as-needed and regularly scheduled doses was not associated with overdose risk after adjustment. Conclusion Among patients receiving opioid prescriptions for pain, higher opioid doses were associated with increased risk of opioid overdose death. JAMA. 2011;305(13):1315-1321 www.jama.com