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Longer duration of opioid use may increase risk for depression

New onset of depression following opioid use was associated with longer duration of use but not dose, according to a retrospective cohort study.

“Depression may be associated with opioid resistance and with opioid misuse. The large population of patients receiving opioid therapy may experience a parallel, yet unrecognized, increase in depression,” Jeffrey F. Scherrer, PhD, of Saint Louis University School of Medicine, and colleagues wrote. “Firmly establishing that greater duration, dose, or both of opioid analgesic use are associated with a new onset of depression, and in diverse patient populations, can inform pain management and public health incentives. A fuller understanding of opioid-related depression is relevant to primary care in light of the increased provision of pain management in this setting.”

Researchers retrospectively assessed patient data from 2000 to 2012 from the Veterans Health Administration (n = 70,997) and from 2003 to 2012 from Baylor Scott & White Health (n = 13,777) and the Henry Ford Health System (n = 22,981) for new opioid users aged 18 to 80 years without depression diagnosis at baseline. Opioid analgesic use duration was defined as 1 to 30 days, 31 to 90 days and more than 90 days. Morphine equivalent dose was defined as 1 mg to 50 mg per day, 51 mg to 100 mg per day and greater than 100 mg per day.

New-onset depression following opioid use occurred among 12% of the Veterans Health Administration (VHA) sample, 9% of the Baylor Scott & White Health (BSWH) sample and 11% of the Henry Ford Health System (HFHS) sample.

New-onset depression occurred more frequently among individuals with longer opioid use, compared with those who used for 1 to 30 days.

Risk for new-onset depression among individuals with 31 to 90 days of opioid use ranged from a hazard ratio of 1.18 (95% CI, 1.1-1.25) in the VHA sample to 1.33 (95% CI, 1.16-1.52) in the HFHS sample.

Among individuals with more than 90 days of opioid use, risk for new-onset depression ranged from hazard ratios of 1.35 (95% CI, 1.26-1.44) in the VHA sample to 2.05 (95% CI, 1.75-2.4) in the HFHS sample.

Dose was not significantly associated with new-onset depression, according to researchers.

“There are several potential mechanisms for our findings. We speculate that long-term opioid analgesic use could lead to hyperalgesia, which in turn leads to a new onset of depression. Chronic opioid use may cause changes in neuroanatomy. Opioid analgesic use lasting 9 years vs. less than 1 year in humans correlated with changes in functional connectivity in the nucleus accumbens and amygdala, regions associated with mood regulation, impulse control, reward, and motivation,” Scherrer and colleagues wrote. “Patients should be informed of this association and be monitored for depression. Clinicians should consider the pain-independent contribution of opioid use when depressed mood develops.” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.