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.
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.
Veterans Health Administration (VHA), 2004 through 2008.
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.
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.
Among patients receiving opioid prescriptions for pain, higher opioid doses were associated
with increased risk of opioid overdose death.