Impact of transitioning from long-term to intermittent opioid therapy on the development of opioid-related adverse outcomes: A retrospective cohort study

Drug Alcohol Depend. 2022 Feb 1;231:109236. doi: 10.1016/j.drugalcdep.2021.109236. Epub 2021 Dec 24.


Background: Increasing pressures exist to reduce or discontinue opioid use among patients currently on long-term opioid therapy (LTOT). It is essential to understand the potential effects of opioid reduction.

Methods: This retrospective cohort study was conducted among veterans with chronic pain and on LTOT. Using 1:1 propensity score-matched samples of veterans switching to intermittent opioid therapy and those continuing LTOT, we examined the development of subsequent substance use disorders (SUD composite; individual SUD types: opioid, non-opioid drug, and alcohol use disorders) and opioid-related adverse outcomes (ORAO composite; individual ORAO types: accidents resulting in wounds/injuries, opioid-related and alcohol/non-opioid medication-related accidents and overdoses, self-inflicted and violence-related injuries). Sensitivity analyses were conducted using logistic regression with stabilized inverse probability of treatment weighting (SIPTW) and instrumental variable (IV) models.

Results: A total of 29,293 veterans switching to intermittent therapy were matched to veterans continuing LTOT. With matched samples, no differences were found in composite SUDs and ORAOs between the groups. With SIPTW, veterans switching to intermittent opioid therapy had higher odds of composite SUDs and ORAOs (SUDs aOR=1.12, 95%CI: 1.07,1.17; ORAOs aOR=1.05, 95%CI:1.00,1.09). IV models found lower risks for composite SUDs and ORAOs among veterans switching to intermittent opioid therapy (SUDs: β = -0.38, 95%CI:-0.63,-0.13; ORAOs: β = -0.27, 95%CI:-0.50,-0.04).

Conclusions: There were no consistent associations between transitioning patients from LTOT to intermittent opioid therapy and the risk of SUDs and ORAOs.

Keywords: Chronic non-cancer pain; Intermittent opioid therapy; Long-term opioid therapy; Opioid-related adverse outcomes; Opioids; Substance use disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcoholism* / drug therapy
  • Analgesics, Opioid / adverse effects
  • Chronic Pain* / drug therapy
  • Chronic Pain* / epidemiology
  • Humans
  • Opioid-Related Disorders* / drug therapy
  • Opioid-Related Disorders* / epidemiology
  • Retrospective Studies


  • Analgesics, Opioid