Increased Risk of Depression Recurrence After Initiation of Prescription Opioids in Noncancer Pain Patients

J Pain. 2016 Apr;17(4):473-82. doi: 10.1016/j.jpain.2015.12.012. Epub 2016 Feb 13.


Several studies have shown that chronic opioid analgesic use is associated with increased risk of new-onset depression. It is not known if patients with remitted depression are at increased risk of relapse after exposure to opioid analgesics. A retrospective cohort design using patient data from the Veterans Health Administration (VHA; n = 5,400), and Baylor Scott & White Health (BSWH; n = 842) was performed with an observation period in the VHA from 2002 to 2012 and in the BSWH from 2003 to 2012. Eligible patients had a diagnosis of depression at baseline and experienced a period of remission. Risk of depression recurrence was modeled in patients that either started taking an opioid or continued without opioid prescriptions before or during remission. Cox proportional hazard models were used to measure the association between opioid use and depression recurrence controlling for pain, and other confounders. Patients exposed to an opioid compared with those unexposed had a significantly greater risk of depression recurrence in both patient populations (VHA: hazard ratio [HR] = 2.17, 95% confidence interval [CI], 2.01-2.34; BSWH: HR = 1.77; 95% CI, 1.42-2.21). These results suggest opioid use doubles the risk of depression recurrence even after controlling for pain, psychiatric disorders, and opioid misuse. Further work is needed to determine if risk increases with duration of use. Repeated screening for depression after opioid initiation may be warranted.

Perspective: In 2 large patient cohorts with large differences in demographic characteristics and comorbidity, patients with remitted depression who were exposed to opioid analgesics were 77% to 117% more likely to experience a recurrence of depression than those who remained opioid -free. Routine, not just at initiation of treatment, screening for depression is warranted.

Keywords: Opioids; depression recurrence; epidemiology; pain; retrospective.

Publication types

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

MeSH terms

  • Adult
  • Analgesics, Opioid / adverse effects*
  • Animals
  • Cohort Studies
  • Depression / chemically induced*
  • Depression / epidemiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Opioid-Related Disorders / epidemiology
  • Opioid-Related Disorders / etiology*
  • Pain / drug therapy*
  • Pain / psychology*
  • Proportional Hazards Models
  • Recurrence
  • United States
  • United States Department of Veterans Affairs


  • Analgesics, Opioid