Prescription opioid use may increase depression risk

Prescription opioid use appeared to increase risk for depression, according to results of a mendelian randomization analysis published in JAMA Psychiatry.

“Literature suggests prescription opioid use increases [major depressive disorder] risk, and while observational findings suggest a potential association between prescription opioid use, MDD, and [anxiety and stress-related disorders], observational data are subject to confounding and reverse causation, making causal inference difficult,” Daniel B. Rosoff, AB, ScB, of NIH’s National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, and colleagues wrote. “Therefore, it remains to be elucidated whether MDD is a cause or consequence of prescription opioid use. While prospective randomized clinical trials are the criterion standard of causal inference, performing RCTs to evaluate the effects of prescription opioid use or other nonopioid pain medications is often complicated by preexisting psychiatric comorbidities.”

In the current study, the investigators used genetically based methods to assess potential bidirectional associations between the genetic liability for prescription opioid and other nonopioid pain medications and both MDD and anxiety and stress-related disorders. They conducted two-sample mendelian randomization using data from genome-wide association studies to investigate whether links existed between the aforementioned disorders and self-reported prescription opioid and nonopioid analgesics, such as NSAIDs and acetaminophen-like derivatives. GWAS data were of 737,473 participants with predominantly European ancestry who were included in the population-based U.K. Biobank and Lundbeck Foundation Initiative for Integrative Psychiatric Research studies.

Results of the single-variable mendelian randomization showed an association between genetic liability for increased prescription opioid use and increased risk for both MDD (OR per unit increase in log odds opioid use = 1.14; 95% CI, 1.06-1.22) and anxiety and stress-related disorders (OR = 1.24; 95% CI, 1.07-1.44). These estimates remained upon using multivariable mendelian randomizations and after accounting for other nonopioid pain medications, as well as in separate models that accounted for comorbid pain conditions. Genetic liability for MDD but not anxiety and stress-related disorders was linked to increased prescription opioid use risk (OR = 1.18; 95% CI, 1.08-1.3), according to bidirectional analyses.

“We provide preliminary genetic evidence that prescription opioid use increases MDD and [anxiety and stress-related disorders] risk, suggesting important clinical consequences,” Rosoff and colleagues wrote. “We also find genetic evidence that MDD is a potential causal risk factor for increased prescription opioid use, which may help identify patient populations to aim prevention strategies to curb the ongoing opioid epidemic.”