New Risks of Prescription Opioids Discovered

Megan Brooks

November 17, 2020

Prescription opioid use increases the risk for major depressive disorder (MDD) and anxiety and stress-related disorders (ASRD), new genetic evidence shows. The findings also suggest MDD is a potential causal risk factor for increased prescription opioid use.   

Taken together, the results "support recommendations that caution is needed with prescribing opioids in settings of mood disorders in favor of nonopioid alternatives, with screening for MDD prior to initiating opioid treatment," write the investigators, led by Falk Lohoff, MD, chief of the Section on Clinical Genomics and Experimental Therapeutics at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in Bethesda, Maryland.

"There is growing observational data suggesting that prescription opioid use may impact depression and anxiety disorders. However, observational studies are subject to confounding, which makes determining both the causal nature and direction of these relationships difficult," Lohoff told Medscape Medical News.

The study was published online November 11 in JAMA Psychiatry.

Prescribe With Caution

The researchers used genetically informed methods to conduct bidirectional analyses investigating the potential causal associations between the genetic liability for prescription opioid and other nonopioid pain medications and both MDD and ASRD. 

The investigators conducted two-sample Mendelian randomization using data from three genome-wide association studies (GWAS) that included more than 737,000 people of predominantly European ancestry.

They found genetic liability for increased prescription opioid use was associated with increased risk of MDD (odds ratio [OR] per unit increase in log odds opioid use, 1.14; 95% CI, 1.06 - 1.22; P < .001) and ASRD (OR, 1.24; 95% CI, 1.07 - 1.44; P = .004).

"Even after accounting for chronic pain — which may confound the results given that opioids are often taken for pain and pain is highly comorbid with psychiatric disorders — the genetic liability for prescription opioid pain medications increased the risk for depression and anxiety disorders," Lohoff added.

Bidirectional analyses showed that genetic liability for MDD but not ASRD was associated with increased prescription opioid use risk (OR, 1.18; 95% CI, 1.08 - 1.30; P < .001).

"Strikingly," the authors write, "nonopioid analgesics had no direct association with the risk for MDD or ASRD."

"While future research is necessary to further investigate these findings, our paper adds to recent observational evidence that prescription opioids should be used with caution as they might influence the risk for depression and anxiety disorders," said Lohoff.

Complex Relationship

Commenting on the findings for Medscape Medical News, Roy H. Perlis, MD, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, noted that the "complex relationship between depression and pain, and the treatments for pain, has been recognized for quite a while."

"What is new about this study is the application of a method that has become widely used to understand such complex relationships using genomic data," said Perlis, who was not associated with the current research.

"Every medicine has risks, and the risks of chronic opioid treatment are all too apparent. This study simply reinforces [that] we need to be cautious in opioid prescribing — whether or not someone has depression," said Perlis.

He cautioned that the study "can't really distinguish the reason for opioid medication use; so it's at least possible that they're simply confirming the relationship between certain kinds of chronic pain, treated with opioids, and depression."

The study was supported by the National Institutes of Health. The study authors have disclosed no relevant financial relationships. Perlis has received consulting fees for service on scientific advisory boards of Belle Artificial Intelligence, Burrage Capital, Genomind, Psy Therapeutics, Outermost Therapeutics, RID Ventures, and Takeda. He holds equity in Psy Therapeutics and Outermost Therapeutics.

JAMA Psychiatry. Published online November 11, 2020. Full text

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