What is the clinical evidence from this study?

Study design: Cohort. Population: New-onset depression in opioid users (n=107755). Intervention: Opioid analgesic use of more than 90 days vs. 1 to 30 days of opioid analgesic use. Primary outcome: New-onset depression (HR 1.35, 95% CI 1.26-1.44).

January 1, 2016Open Access

Prescription Opioid Duration, Dose, and Increased Risk of Depression in 3 Large Patient Populations

JSJeffrey F. ScherrerUniversidade Federal de Minas Gerais JSJoanne SalasUCLouvain Saint-Louis Brussels LCLaurel A. CopelandUniversity of Massachusetts Chan Medical School

Key Result

Opioid analgesic use of more than 90 days, compared with 1 to 30 days, was associated with a significantly increased risk of new-onset depression across three large patient populations (HR ranging from 1.35 to 2.05).

Study Design

Type

Cohort (n=107,755)

Multicenter

Yes

Structured PICO

Does longer duration of opioid analgesic use increase the risk of new-onset depression in new opioid users?

Population

107,755 adult new opioid users aged 18 to 80 years, without a baseline diagnosis of depression, cancer, or HIV, followed across three large US health care systems.

Exposure

Opioid analgesic use for 31 to 90 days, or more than 90 days.

Comparator

Opioid analgesic use for 1 to 30 days.

Outcome

New-onset depression (defined by 2 or more outpatient diagnoses or 1 or more inpatient diagnoses).safety

Opioid analgesic use of longer than 30 days is associated with an increased risk of new-onset depression, independent of dose, suggesting that prolonged opioid therapy may contribute to depression.

Main Result

Hazard Ratio: 1.35 (95% CI 1.26–1.44)

Absolute Event Rate: 14.4% vs 11.6%

Limitations

Duration of opioid use did not account for intermittent opioid administration by patients and frequency of dose escalation.
Self-report bias is a possible limitation because patients seeking opioids and those with poor mood may report more pain.
Lack of statistical power to model use of longer than 180 days in private sector data.
Residual confounding, especially in the case of maximum dose, may be present.
New-onset depression may have developed during or after opioid use cessation.

Abstract

PURPOSE: Recent results suggests the risk of a new onset of depression increases with longer duration of opioid analgesic use. It is unclear whether new-onset depression related to opioid analgesic use is a function of the dose prescribed or the duration of use or both. METHODS: Using a retrospective cohort design, we collected patient data from 2000 to 2012 from the Veterans Health Administration (VHA), and from 2003 to 2012 from both Baylor Scott in opioid analgesic use of more than 90 days, it ranged from HR = 1.35 (95% CI, 1.26-1.44) in VHA to HR = 2.05 (95% CI, 1.75-2.40) in HFHS. Dose was not significantly associated with a new onset of depression. CONCLUSIONS: Opioid-related new onset of depression is associated with longer duration of use but not dose. Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression. Opioid analgesic use, not just pain, should be considered a potential source when patients report depressed mood.

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