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The surprising link between prescription opioids + anxiety

Find out how prescription opioids interact with anxiety and related disorders to better understand how to treat pain and manage stress.

Ophelia team
Rx opioids and anxiety
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Arthur Robin Williams, MD

The surprising link between prescription opioids + anxiety

Anxiety-related symptoms and disorders are among the most common mental health problems facing the U.S. population, and the rates of co-occurrence of anxiety and opioid use disorder (OUD) are strikingly high. This has left many wondering what the relationship is between opioid use and anxiety and how prescribing opioids for pain relief could be affecting those with anxiety. It’s crucial to understand how prescription opioids interact with anxiety and related disorders to better understand how to treat pain, manage stress and mitigate the dangers of the opioid crisis

Does oxycodone cause anxiety?

To understand how opioid use can impact anxiety, it’s first necessary to understand how opioids act in the brain and how that relates to mental health. Oxycodone is one of the most commonly prescribed opioids for medical use, especially for pain management, and it works by binding with opioid receptors in the brain. These neurons control the body’s response to pain signaling. Activating opioid receptors inhibits a cell’s ability to send those signals, thereby reducing feelings of pain. However, another effect of the opioid receptors activating is a decrease in the body’s production of norepinephrine. This hormone controls blood pressure and alertness, and its presence is associated with fear responses.

When a patient takes opioids, the hormone that produces feelings of fear is reduced, which means that opioids can alleviate not only pain but also anxiety. However, as the body processes oxycodone and filters it out of the bloodstream, it produces norepinephrine again at normal levels. This causes alertness and blood pressure to rise, which can reignite a patient’s anxiety, even if they’re not in a situation during which they usually feel anxious. This can lead to a cycle of relief while taking opioids and increased anxiety as the drug wears off, which can also build dependence.

It’s also possible that sustained opioid use can train the brain to chronically overproduce norepinephrine in response to its suppression via opioids, leading to heightened and prolonged anxiety. This could lead to a patient with no history of anxiety developing the condition

Additionally, anxiety is a known side effect of opioid withdrawal. Opioids generally cause active feelings of euphoria, happiness, and elation, and the effects of withdrawal from physically addictive substances are often the opposite of the active effects of the drug. In the case of opioids, withdrawal can be severely painful, cause anxiety and cause flu-like symptoms, such as tremors, hot flashes, and nausea. 

Do people use oxycodone for anxiety?

Prescription opioids, such as oxycodone, are not approved for use as an anxiety treatment, and it’s highly unlikely that any doctor would prescribe them to a patient for such use. However, it’s well-known that mental health disorders like anxiety and depression can increase a patient’s perception of physical pain, which may mean those with anxiety are more likely to be prescribed an opioid for pain management. The result is that doctors could be inadvertently prescribing oxycodone for anxiety instead of just pain.

According to one 2019 study, over 60% of individuals with OUD also report having an anxiety-related disorder. The study also suggests that anxiety and related disorders could be an instigating factor in developing an opioid use disorder. This raises the possibility that a non-negligible number of people with current and past opioid use disorders developed OUD while using oxycodone and other prescription opioids to self-medicate for their anxiety-related disorder, whether intentionally or not. 

The co-occurrence of anxiety disorders and opioid misuse also alters treatment outcomes in affected patients. Medication for addiction treatment (MAT) is one of the most effective ways to manage opioid addiction, reduce the risk of overdose, and address withdrawal. Still, MAT is less effective when the patient also experiences an anxiety disorder. Elevated anxiety at the onset of MAT use leads to higher relapse rates. 

What is opioid-induced depression?

Another anxiety-related disorder that can arise in those with opioid use disorder is known as opioid-induced depression. Opioid-induced depression is of particular concern because of its resistance to standard depression treatment. When opioids are taken for extended periods, a patient’s risk of developing treatment-resistant depression (TRD) increases. 

This condition results after chronic opioid use disrupts the body’s natural dopamine levels, causing them to remain extremely high for extended periods. This causes the euphoric feelings of opioid use. But once the opioid wears off, the patient’s dopamine production centers may be exhausted and unable to produce enough dopamine to match baseline levels. This results in chronically low dopamine, which is associated with depression and prevents a patient from feeling joy or excitement to the same degree as they did previously.

Evidence-based treatment that puts your mind and body first

Ophelia’s clinical care team makes your unique needs a priority. Our goal is to ensure you get the support you need while undergoing MAT—and that includes understanding your mental health needs and providing treatments for co-occurring anxiety, depression, PTSD, and sleep disorders. Schedule an introductory call and learn more about our comprehensive telehealth model.


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