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Prescription Opioid Analgesics Increase the Risk of Depression

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Prescription opioid analgesic use has quintupled recently. Evidence linking opioid use with depression emanates from animal models and studies of persons with co-occurring substance use and major depression. Little is known about depressogenic effects of opioid use in other populations.


The purpose of this study was to determine whether prescription opioids are associated with increased risk of diagnosed depression.


Retrospective cohort study, new user design.


Medical record data from 49,770 US Department of Veterans Affairs (VA) health care system patients with no recent (24-month) history of opioid use or a diagnosis of depression in 1999 and 2000.


Propensity scores were used to control for bias by indication, and the data were weighted to balance the distribution of covariates by duration of incident opioid exposure. Cox proportional hazard models with adjustment for painful conditions were used to estimate the association between duration of prescription opioid use and the subsequent risk of development of depression between 2001 and 2007.


Of 49,770 patients who were prescribed an opioid analgesic, 91 % had a prescription for < 90 days, 4 % for 90–180 days, and 5 % for > 180 days. Compared to patients whose prescription was for < 90 days, the risk of depression increased significantly as the duration of opioid prescription increased (HR = 1.25; 95 % CI: 1.05–1.46 for 90–180 days, and HR = 1.51; 95  % CI:1.31–1.74 for > 180 days).


In this sample of veterans with no recent (24-month) history of depression or opioid analgesic use, the risk of development of depression increased as the duration of opioid analgesic exposure increased. The potential for depressogenic effect should be considered in risk-benefit discussions, and patients initiating opioid treatment should be monitored for development of depression.

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This work was supported by a VA HSR&D Career Development Award-2 granted to Jeffrey F. Scherrer, Ph.D. The funding agency had no role in the design or conduct of the study, data analysis and interpretation, preparation of the manuscript, and review or approval of the manuscript. Dr. Scherrer had full access to all the data in the study and takes responsibility for data integrity and the accuracy of the data analysis.

Conflict of Interest

The authors declare that they do not have a conflict of interest.

Funding Source

Veteran’s Administration Career Development Award to Dr. Scherrer

Statement of Authorship

All authors had access to aggregate data and contributed to writing the manuscript.

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Correspondence to Jeffrey F. Scherrer PhD.

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e-Table 1

ICD-9-CM codes used to define diagnoses (DOCX 16 kb)

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Scherrer, J.F., Svrakic, D.M., Freedland, K.E. et al. Prescription Opioid Analgesics Increase the Risk of Depression. J GEN INTERN MED 29, 491–499 (2014).

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