Long-Term, Frequent Opioid Use Associates With New-Onset Depression

close up of a group of white tablets with an out of focus prescription bottle in the background
Long-term opioid therapy was associated with increased risk for new-onset depression in a recently published retrospective cohort study.

Long-term opioid therapy was associated with increased risk for new-onset depression. These findings, from a retrospective cohort study, were published in the journal Pain.

Investigators from Saint Louis University, Missouri, sourced data from the Optum analytics database of electronic health records. Patients who filled a new ³90-day opioid medication between 2011 and 2016 (N=5146) were assessed for depression.

A propensity-matching approach was used to balance cohorts of patients on the basis of opioid use intensity, in which occasional use was defined as <50% days covered, intermittent as 50%-<80% days covered, frequent use as 80%-<90% days covered, and daily as ³90% days covered.

The new opioid users were aged mean 54.5±13.6 years, 55.7% were women, 72.5% were White, 25.0% had high healthcare utilization, 70.5% had back pain, 66.6% arthritis, and 64.8% muscle pain. The patients were taking a maximum morphine milligram equivalents (MME) of <50 (48.4%), 51-90 (24.6%), 91-180 (16.6%) or >180 (10.4%) MME.

The patients were stratified by occasional (n=582), intermittent (n=1661), frequent (n=664), and daily (n=2239) use. These cohorts differed significantly for age (P =.001), geographic location (P =.020) and comorbidities, in which more patients with arthritis were intermittent users (P <.001), more with back pain were daily users (P <.001), and more with muscle pain were occasional users (P <.001).

There was a total of 1376 (26.7%) instances of new-onset depression, corresponding with a rate of 88.7 per 1000 person years. Stratified by use intensity, the cumulative incidence was highest among daily users (30.4%) followed by frequent (28.5%), occasional (23.2%), and intermittent (22.4%) users.

In the fully adjusted model, new onset depression was associated with opioid abuse or dependence (adjusted hazard ratio [aHR], 1.95; 95% CI, 1.54-2.47), daily use (aHR, 1.35; 95% CI, 1.09-1.67), and frequent use (aHR, 1.31; 95% CI, 1.03-1.67).

This study was limited by not having access to information about consumption of opioid medications.

The study authors concluded that patients who received long-term opioid therapy were at increased risk for new-onset depression, especially when using opioids ³80% of the time. Additional study is needed to assess whether nonpharmacological management may reduce risk for depression.


Scherrer JF, Salas J, Miller-Matero LR, et al. Long-term prescription opioid users’ risk for new onset depression increases with frequency of Use. Pain. Published online Novemebr 30, 202. doi:10.1097/j.pain.0000000000002547