The association of opioid use duration and new depression episode among patients with and without insomnia

J Opioid Manag. 2020 Sep/Oct 2020;16(5):317-328. doi: 10.5055/jom.2020.0587.


Objective: Insomnia commonly co-occurs with depression, chronic pain, and opioid use. Both insomnia and chronic opioid analgesic use (OAU) are independent risk factors for a new depression episode (NDE). This study determined if the association between longer OAU duration and NDE was stronger in those with versus without insomnia.

Design: Retrospective cohort.

Setting: Veterans Health Administration electronic medical records (2000-2012).

Participants: New opioid users in follow-up (2002-2012), free of depression for two years prior to follow-up, and aged 18-80 (n = 70,997).

Methods: NDE was ≥ 2 ICD-9 codes in a 12-month period. Insomnia before OAU initiation was ≥1 ICD-9 code. Cox proportional hazard models stratified on insomnia assessed the relationship between initiating a 1-30, 31-90, or > 90 day period of OAU and NDE while controlling for confounders using inverse probability of treatment-weighted propensity scores (PS).

Results: Compared to 1-30 day OAU, 31-90 day was associated with NDE in those without (HR = 1.20; 95 percent CI: 1.12-1.28) but not with insomnia (HR = 1.06; 95 percent CI: 0.86-1.32). Results showed a stronger effect of chronic (>90) OAU in those with insomnia (HR = 1.59; 95 percent CI: 1.27-1.98) compared to those without (HR = 1.31; 95 percent CI: 1.21-1.42). However, all stratum-specific effects were not significantly different (p = 0.136).

Conclusions: Although stratum-specific risks were statistically similar, there was evidence for a trend that chronic OAU is a stronger risk factor for NDE in those with versus without insomnia. Providers are encouraged to monitor sleep impairment among patients on opioid therapy, as sleep may be associated with greater risk for NDE in patients with chronic OAU.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / therapeutic use
  • Cohort Studies
  • Depression / chemically induced*
  • Depression / epidemiology
  • Depression / psychology*
  • Humans
  • Middle Aged
  • Prescription Drugs / adverse effects*
  • Retrospective Studies
  • Sleep Initiation and Maintenance Disorders / epidemiology*
  • United States / epidemiology
  • United States Department of Veterans Affairs
  • Veterans / psychology
  • Veterans Health Services
  • Young Adult


  • Analgesics, Opioid
  • Prescription Drugs