Opioid use increases depression, anxiety risk, study shows

David Heitz


(Francisco Gonzalez/Unsplash)

A study published this week in JAMA Psychiatry shows prescription opioid use sometimes is to blame for symptoms of depression and anxiety-related stress.

This is especially true in people with a genetic propensity toward opioid use who suffer from symptoms of depression.

Daniel B. Rosoff of the section on clinical genomics and experimental therapeutics at National Institute on Alcohol Abuse and Alcoholism led the study.

“While further work is needed, this genetics-based study supports conventional observational literature suggesting prescription opioid use increases the risk for depression,” the authors observed.

“Growing evidence suggests that prescription opioid use affects depression and anxiety disorders; however, observational studies are subject to confounding, making causal inference and determining the direction of these associations difficult.”

Researchers compare opioid, depression link to NSAIDS

In an original investigation, Rosoff and colleagues used statistics from genome-wide association studies to assess potential associations of self-reported prescription opioid and nonopioid analgesics, including nonsteroidal anti-inflammatories (NSAIDs) and acetaminophen-like derivatives. The data were derived from participants of predominantly European ancestry.

More than 700,000 people were studied. More than half included women.

“The findings of this mendelian randomization analysis suggest evidence for potential causal associations between the genetic liability for increased prescription opioid use and the risk for major depressive disorder and anxiety- and stress-related disorders,” the authors concluded. “While replication studies are necessary, these findings may inform prevention and intervention strategies directed toward the opioid epidemic and depression.”

Opioid use epidemic in the United States

During the past two decades, opioid use in the United States has exploded and now is at epidemic proportions. Opioid use increased five-fold during the past 20 years. Hundreds of thousands of people have died of overdose. More than two-thirds of the more than 700,000 overdose deaths from 2013 to 2017 involved opioids.

“It is also reported that prescription opioids (vs. illicit opioids) are the first opioids to be misused, with almost 30 percent of patients prescribed opioids for chronic pain misusing them and about 12 percent developing opioid use disorder,” the authors reported.

It is estimated that of the almost 8 million people in the United States with psychiatric disorders more than half receive most of the 200 million opioid prescriptions written each year.

Individuals with psychiatric problems are more likely to report long-term opioid use. “Informed prescribing practices require comprehensive understanding of the treatment’s risks and benefits, and while opioids alleviate pain, chronic use is associated with numerous adverse effects, including immunosuppression, natural reward processes dysregulation, and neurohormonal deficits,” the authors observed.

“Observational studies have also found opioid use to be highly comorbid with both major depressive disorder and anxiety- and stress-related disorders.”

Doctors use caution prescribing opioids to depressed people

Previous studies already have resulted in doctors avoiding prescribing opioids to people with depression. A study that appeared in the Clinical Journal of Pain in 2018 showed “Depressed patients seem to continue opioid use at lower pain intensity levels and higher levels of physical function than do nondepressed patients.”

The study was conducted by Mark Sullivan. Sullivan teaches at the University of Washington, Seattle, in the departments of psychiatry and behavioral sciences, anesthesiology and pain medicine, bioethics and humanities.

“In studies that carefully control for confounding by indication, it has been shown that long-term opioid therapy increases the risk of incident, recurrent, and treatment-resistant depression,” Sullivan concluded. “Depressed patients may tend to overuse opioids because they use them to treat insomnia and stress. Depression also seems to increase the risk of abuse or nonmedical use of prescription opioids among adults and adolescents.”

What’s the mechanism of action between opioids, depression?

The researchers of the study appearing in JAMA Psychiatry this week said that “strikingly, nonopioid analgesics had no direct association with the risk of major depressive disorder or anxiety- and stress-related disorder.” The researchers adjusted for pain and other variables.

“We evaluated potential bidirectional associations between the genetic liability for prescription opioid and nonopioid pain medication use and both major depressive disorder and anxiety- and stress-related disorder and found genetic evidence that prescription opioid use was associated with increased major depressive disorder and anxiety- and stress-related disorder risk,” the authors concluded.

Researchers are trying to understand the mechanism of action involved in opioids and depression.

“The underlying mechanisms of prescription opioids in the pathophysiology of major depressive disorder remain to be elucidated, but potentially include opioid-induced dysregulation of reward circuitry that results in reduced reward perception or pleasure and relief generation or other physical medical dysregulation (i.e., endocrine and autonomic nervous system abnormalities) that potentially contributes to the physical symptoms of major depressive disorder,” the authors of the report in JAMA Psychiatry wrote.

“Notably, it has been suggested that the endogenous opioid system is directly involved in the regulation of mood and the dysregulation of that system may factor into depression and anxiety….”

Researchers find depressed people keep using opioids

Finding a link between opioids and depression is troublesome because the tail usually wags the dog. Both feed off each other.

“Our findings support recommendations that caution is needed with prescribing in settings of mood disorders in favor of nonopioid alternatives, with screening for major depressive disorder prior to initiating opioid treatment,” the authors advised.

In conclusion, the authors provided preliminary genetic evidence that prescription opioid use increases major depressive disorder and anxiety- and stress-related disorder risk. “We also find genetic evidence that major depressive disorder 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,” the authors wrote.

Find opioid abuse treatment with help from SAMSHA

“Opioids are a class of drugs that include the illegal drug heroin, synthetic opioids such as fentanyl, and pain relievers available legally by prescription, such as oxycodone (OxyContin), hydrocodone (Vicodin), codeine, morphine, and many others,” SAMSHA reports.

SAMSHA says opioids also are known as “Happy Pills, OC, Oxy, Oxycotton, Percs and Vikes.”

If you are one of the millions of Americans addicted to opioids, you can call 800-662-HELP or click here for the treatment locator provided by the Substance Abuse and Mental Health Services Administration, or SAMSHA.

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I have been in the news business more than 30 years, spending much of my career at some of the best local newspapers in the country. Today, I report on Denver City Hall, homelessness and other topics for NewsBreak, much like I did in my twenties covering Newport Beach, Calif. for the Daily Pilot. I consider myself a lucky guy to still be doing what I love after so many years.

Denver, CO

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