Can SSRIs Interfere With Opioid Pain Relief?

By Kelly Burch 02/12/19

A new study examined whether patients who were on SSRIs received less pain relief from certain opioids.

Woman taking an SSRI

SSRIs—the most common type of antidepressant—can make some opioid pain relievers less effective, exposing patients to higher levels of pain, according to a new study. 

For the study, published in the journal PLOS ONE, researchers examined medical records of 4,300 patients who underwent a major operating room procedure at a medical center between 2009 and 2016. They found that patients who were on SSRIs and who received a certain type of opioid had less pain relief following their operations. 

To understand the study, it’s important to note that opioids come in two varieties, according to NPR. Direct opioids, including morphine and OxyContin, begin working as soon as they are administered. Prodrugs, which include Vicodin and hydrocodone, have to be broken down in the liver before they can begin relieving pain. 

SSRIs interrupt this process. This is because they affect a liver enzyme that is needed to break down prodrugs. With less of the enzyme breaking down drugs, the pain relief is less effective. 

"There was theoretical evidence that suggested SSRIs might block prodrug opioids, but we didn't know if it actually affected patient outcomes," said Tina Hernandez-Boussard, who authored the study. 

People on SSRIs who were prescribed prodrug opioids were in more pain up to two months after their procedure. 

Because SSRIs and opioids are some of the most common prescriptions in the country, the study could have widespread implications for how pain is handled, said Jenny Wilkerson, a professor who teaches pharmacodynamics at the University of Florida.

"This is an important study,” she said, before calling for additional research. 

People who get less effective pain relief from opioids are likely to take more pills, which "could lead to misuse or abuse down the road,” Hernandez-Boussard said. 

"If the opioids aren't being activated and you're not getting appropriate pain management, you're going to take more opioids and you're going to take them for a longer period of time," she said. 

One way around this would be to prescribe direct-acting opioids to patients on SSRIs. 

"Every opioid has a side effect, not one opioid that is better than another. Possibly for patients taking SSRI, morphine or oxycodone, direct-acting drugs which don't need to be broken down by the liver might be a better choice,” Hernandez-Boussard said. 

Wilkerson said that patients should be confident in advocating for themselves when it comes to effective pain relief. 

"Patients shouldn't feel stigmatized for being depressed or in pain. Patients have to advocate for their best personal care.”

However, Hernandez-Boussard acknowledged that this can be difficult for people who are depressed. Instead, she believes the medical community should work to better understand the interaction of SSRIs and opioids. 

She said, “We need to think about how we can tailor treatment towards more vulnerable groups. More work needs to be done, but this is a good first step."

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Kelly Burch writes about addiction and mental health issues, particularly as they affect families. Follow her on TwitterFacebook, and LinkedIn.