Relationship between concomitant benzodiazepine-opioid use and adverse outcomes among US veterans

Pain. 2018 Mar;159(3):451-459. doi: 10.1097/j.pain.0000000000001111.


Benzodiazepines and opioids are commonly used among veterans suffering from mental health disorders and pain conditions. The objective of this study is to determine whether concomitant benzodiazepine-opioid use increases the incidence of adverse outcomes above the baseline risk of nonacute opioid-only use. The dataset contained all veterans who filled at least 1 opioid prescription during the years 2008 to 2012. Nonacute opioid use was defined as having opioid prescriptions greater than or equal to 20 days within a 60-day period. Concomitant use was defined as having opioid and benzodiazepine prescriptions that overlapped for at least 7 days. Nonacute opioid-only users were matched to concomitant opioid-benzodiazepine users based on propensity scores. A 365-day observation period was used to identify adverse outcomes. The primary outcome examines the existence of one or more of the following outcomes: opioid-related accidents and overdoses, alcohol- and nonopioid drug-related accidents and overdoses, self-inflicted injuries, violence-related injuries, wounds/injuries overall, and death. A logistic propensity score adjusted regression controlling for propensity toward concomitant use was used to determine the association of concomitant use with adverse outcomes. The final matched sample consisted of 396,141 nonacute opioid-only using veterans and 48,971 concomitant benzodiazepine-opioid users. Receiving opioids and benzodiazepines concomitantly increased the risk of experiencing an adverse outcome with an odds ratio of 1.359 (95% confidence interval: 1.320-1.400; P < 0.0001). Among veterans receiving opioids, concomitant benzodiazepine use is associated with an increased risk of adverse outcomes when compared to the baseline risk of opioid-only using veterans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / adverse effects*
  • Antipsychotic Agents / adverse effects*
  • Benzodiazepines / adverse effects*
  • Cohort Studies
  • Drug Interactions
  • Drug Overdose / epidemiology*
  • Drug Overdose / etiology*
  • Drug Prescriptions / statistics & numerical data
  • Female
  • Humans
  • Male
  • Mental Disorders / drug therapy
  • Middle Aged
  • Odds Ratio
  • Pain / drug therapy
  • Time Factors
  • United States / epidemiology
  • Veterans*
  • Young Adult


  • Analgesics, Opioid
  • Antipsychotic Agents
  • Benzodiazepines