December 3, 2023

Antidepressants Are Reducing the Effectiveness of Opioids

Author: The Great Courses Staff
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By The Great Courses Staff

New research suggests that antidepressants such as Zoloft and Prozac interfere with many opioids. However, antidepressants and opioids are two of the most commonly prescribed kinds of drugs in the United States. The medical community needs a solution.

White pills on light blue background

The academic journal PLOS ONE published a study in early February 2019 explaining the relationship between both kinds of drugs. Scientists discovered that common antidepressants limit the effectiveness of pain relief in one of the two kinds of opioids. This research underscores increasing demands to address the opioid addiction crisis in the United States, since some patients may ingest more painkillers to compensate. Let’s figure out how we got here.

How Opioid Use Became Opioid Abuse 

Drug overdose is now the leading cause of death in Americans under 50 years old. Opioids—drugs that produce similar effects as opium and its by-products morphine and codeine—top the list. Common opioids include Vicodin, Percocet, and heroin. “Opioids have been around for thousands of years,” said Dr. Thad Polk, Professor in the Department of Psychology and the Department of Electrical Engineering and Computer Science at the University of Michigan. “They’ve been the gold standard medical treatment for pain since the Civil War. But in the 1990s, something changed. Pharmaceutical companies began actively promoting the use of opioids in the long-term treatment of chronic pain, based on the beliefs that patients were unlikely to become addicted.”

However, they did. Dr. Polk explained that opioid prescriptions got so far out of hand that in 2016 a dozen U.S. states had more opioid prescriptions than residents. Addiction levels spiked. According to Dr. Polk, 25% of patients with opioid prescriptions misuse them—and 80% of heroin users say that painkillers were the first drug they misused. Now, the number of opioid addicts in the United States exceeds two million.

These drugs stimulate a specific series of receptors in the brain. These receptors release large amounts of the neurotransmitter dopamine. Dopamine affects parts of the brain that relate to intense craving and rewards. “Those bursts of dopamine are what makes opioids, and all other drugs of abuse, so addictive,” Dr. Polk said.

Antidepressants, Opioids, and the Liver

Two kinds of opioids exist. Drugs like morphine and oxycodone work directly on your body. Other drugs, like hydrocodone, must be metabolized in the liver before they relieve pain. These are called “prodrugs.” Vicodin and other widespread prescription painkillers contain hydrocodone.

Meanwhile, Prozac and Zoloft are two of the most commonly prescribed antidepressants. Both of these antidepressants are selective serotonin reuptake inhibitors, or SSRIs. SSRIs limit the activity of an enzyme in your liver that processes prodrug opioids. As the liver fails to properly metabolize these opioids, their pain relief and releases of dopamine suffer. If the positive effects of opioids suddenly diminish, regular patients and addicts may take higher doses to attain the same euphoria or pain relief they experienced previously. Unfortunately, since prodrugs and SSRI’s are so commonly prescribed, millions of Americans remain at risk of addiction.

Dr. Polk suggests that the best chance of countering opioid addiction is to treat pain with safe and non-addictive substances. “There are a few promising candidates on the horizon,” Dr. Polk said. “Drugs called ‘biased antagonists’ seem to be able to bind to opioid receptors in the pain pathways without producing the undesirable effects on breathing and the reward circuit. Non-opioid approaches like medical marijuana and brain stimulation have also shown promise.”

Although opioids are addictive—and exacerbated by SSRI’s like Zoloft—the medical industry has alternatives to pursue. For now, we must hope they arrive in time.

Dr. Thad A. Polk contributed to this article. Dr. Polk is an Arthur F. Thurnau Professor in the Department of Psychology and the Department of Electrical Engineering and Computer Science at the University of Michigan. He received a B.A. in Mathematics from the University of Virginia and an interdisciplinary Ph.D. in Computer Science and Psychology from Carnegie Mellon University. 

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