Nonmedical Opioid Use Linked to Symptoms of Major Depressive Disorder

In the cohort without baseline MDD, baseline nonmedical opioid use was significantly associated with an increased risk of incident depressive symptoms, but not MDD, over 3 years.

Pre-existing major depressive disorder (MDD) and depressive symptoms increase the risk of nonmedical opioid use (NMOU), whereas pre-existing NMOU increases the risk of new onset symptoms of depression, according to the results of a study published in the Journal of Affective Disorders.

A co-occurrence of NMOU and mental disorders may predict poor treatment outcomes for both disorders, as well as high healthcare utilization and medical costs. However, despite an increased risk of NMOU in patients with pre-existing MDD, the literature on the risk of incident MDD due to NMOU is inconclusive.

Xue Li, a PhD candidate at the department of epidemiology and biostatistics, College for Public Health and Social Justice, Saint Louis University, St. Louis, Missouri, and colleagues derived data from Wave 1 and Wave 2 of the National Epidemiological Survey on Alcohol and Related Conditions (N=23,214). They applied logistic regressions to explore whether a baseline MDD diagnosis and symptoms of MDD affect new onset of NMOU, as well as the role of baseline NMOU in raising the risk of MDD.

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After controlling for baseline demographic characteristics, family history, alcohol use disorders, nicotine dependence, body pain, and comorbid psychiatric disorders, a baseline diagnosis of MDD was associated with higher odds (adjusted odds ratio [aOR], 1.68; 95% CI, 1.43-1.98) of new onset NMOU over 3 years compared to no MDD at baseline. Any baseline symptoms of MDD were also associated with higher odds (aOR, 1.25; 95% CI, 1.14-1.38) of having incident NMOU at follow-up.

In the cohort of participants who did not have MDD at baseline, baseline NMOU was significantly associated with an increased risk of incident major depressive symptoms over 3 years (aOR, 1.42; 95% CI, 1.23-1.63). However, baseline NMOU demonstrated lowered odds of incident MDD over 3 years (aOR, 0.79; 95% CI, 0.66-0.94).

Limitations included the potential underestimation of opioid use, and confounding factors affecting the relationship between NMOU and MDD, such as lack of social support, social impairment, or personality factors, which were not included in the study.

The researchers noted, “Early identification and intervention on the progress of major depression among opioid users may reduce non-medical opioid use. Besides, opioid misuse monitoring programs targeting people suffering from depression help alleviate their mental conditions.”


Li X, Fu Q, Scherrer JF, Humphrey D, Leigh I. A temporal relationship between nonmedical opioid use and major depression in the U.S.: a prospective study from the National Epidemiological Survey on Alcohol and Related Conditions. J Affect Disord. 2020;273:298-303.