The findings may be explained by long-term opioid use leading to changes in neuroanatomy and low testosterone, among other possible biological explanations, researchers said.
The link was independent of the known contribution of pain to depression, and the study calls on clinicians to consider the contribution of opioid use when depressed mood develops in their patients.
"Opioid-related new onset of depression is associated with longer duration of use but not dose," said Jeffrey Scherrer, associate professor at Saint Louis University in US.
The study calls for additional research to identify which patients are most vulnerable to opioid-related depression.
Researchers collected patient data from 2000-2012 from the Veterans Health Administration (VHA), Baylor Scott and White Health (BSWH), and the Henry Ford Health System (HFHS).
The data sets were comprised of 70,997 VHA patients, 13,777 BSWH patients and 22,981 patients from HFHS. The patients were new opioid users, ages 18 to 80, without a diagnosis of depression when they began taking medication.
"Findings were remarkably consistent across the three health care systems even though the systems have very different patient characteristics and demographics," Scherrer said.
In all three patient populations, longer duration of opioid analgesic use was associated with new-onset depression after controlling for pain and daily morphine equivalent doses.
The researchers said that study on the efficacy of opioids in depression treatment, while limited by small samples, short follow-up times and lack of control groups, does not support opioids as an effective long-term treatment for depression.
The study was published in the journal Annals of Family Medicine.
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