Rapid Increase in Opioid Dose Increases Risk of New-Onset Depression

high doses
high doses
Dose escalation may be a proxy for loss of control or undetected abuse known to be associated with depression.

Rapid increases in prescription opioid dose may lead to higher rates of new-onset depression (NOD), according to a study published in Pain.1

Increasing the dose of prescription opioids over time is a predictor for NOD.2 But whether high daily doses or rapid rates of dose increase account for this association is unclear.1 Data on the role of maximum opioid dose in NOD risk is conflicting, possibly due to differences in rates of opioid dose change.3

In the current study, investigators evaluated whether the rate of opioid dose change plays a role in the risk of NOD using data from 7051 patients with recent chronic opioid use (defined as >90 days initial use) in the Veterans Health Administration electronic health record.

Opioid doses were standardized by converting them to morphine equivalent doses (MED). Rates of opioid dose changes were classified as follows: stable, decrease, slow increase, and rapid increase.

The incidence rate of NOD was highest in the rapid increase group (27.5 cases per 1000 person-years) and lowest in the stable group (13.0 cases per 1000 person-years).

Faster rates of opioid dose escalation were associated with increasing NOD risk after adjusting for confounding factors, such as psychiatric comorbidities and maximum monthly dose. Patients whose opioid dose was slowly increased had a higher risk of NOD than patients whose dose remained stable (hazard ratio [HR], 1.22); the risk of NOD was even higher in patients whose opioid dose was rapidly increased (HR, 1.58).

The risk of NOD was also significantly greater in the slow increase and rapid increase groups, compared with the decrease group.

Summary and Clinical Applicability

High opioid doses are associated with a greater risk for NOD, but whether high daily doses or rapid rates of dose increase contribute to this risk is unclear. Researchers evaluated the relationship between rate of opioid dose change and NOD in the Veterans Health Administration population.

“Faster rates of MED escalation contribute to NOD, independent of maximum dose, pain, and total opioid duration,” the researchers wrote. “Dose escalation may be a proxy for loss of control or undetected abuse known to be associated with depression. Clinicians should avoid rapid dose increase when possible and discuss risk of depression with patients if dose increase is warranted for pain.”

Limitations and Disclosures

The results may not be generalizable since the study population consisted of veterans who were mostly male, and had more physical and psychiatric comorbidities than the general population

Opioid prescription fills were used as a proxy for opioid use and may not reflect actual opioid use

The investigators report financial relationships with Mallinckrodt Pharmaceuticals, Veterans Health Administration, Opioid PMR Consortium, and Chrono Therapeutics.

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  1. Salas J, Scherrer JF, Schneider FD, et al. New-onset depression following stable, slow, and rapid rate of prescription opioid dose escalation. Pain. 2017;158(2):306-312. doi: 10.1097/j.pain.0000000000000763
  2. Scherrer JF, Salas J, Lustman PJ, Burge S, Schneider FD; Residency Research Network of Texas (RRNeT) Investigators. Change in opioid dose and change in depression in a longitudinal primary care patient cohort. Pain. 2015;156(2):348-355. doi: 10.1097/01.j.pain.0000460316.58110.a0
  3. Scherrer JF, Salas J, Copeland LA, et al. Prescription opioid duration, dose, and increased risk of depression in 3 large patient populations. Ann Fam Med. 2016;14(1):54-62. doi: 10.1370/afm.1885

This article originally appeared on Clinical Pain Advisor