A new study reveals that several common antidepressants, including fluoxetine (Prozac), paroxetine (Paxil) and bupropion (Wellbutrin), interact with the opioid pain medication tramadol to blunt pain relief.

The findings, published in the journal Pharmacotherapy, have important implications for the opioid epidemic, suggesting that some patients suspected of drug-seeking may in fact be under-medicated and are simply seeking more effective pain relief. In addition, the results may explain why some patients exceed the prescribed dose of tramadol, thereby increasing their risk of addiction.

For the study, researchers from University Hospitals (UH) analyzed the medication records of 152 patients at UH Cleveland Medical Center and UH Geauga Medical Center who had received scheduled tramadol for at least 24 hours. All of the participants had been admitted as inpatients or were under observation status.

The findings show that patients who were taking fluoxetine, paroxetine or bupropion required three times more pain medication per day to control “breakthrough” pain throughout the day, compared with patients not taking those antidepressants.

“As we looked at in secondary analysis, it ended up being four times as much over their entire hospital stay,” said Derek Frost, Pharm.D., lead author of the study.

Prior research with healthy volunteers has shown effects on blood levels when combining tramadol with these particular antidepressants. However, this study is the first to document the effects of this interaction in a real-world setting with patients.

“We knew that there was a theoretical problem, but we didn’t know what it meant as far as what’s happening to pain control for patients,” Frost said.

What explains the interaction between tramadol and these antidepressants?

“Tramadol relies on activation of the CYP2D6 enzyme to give you that pain control,” Frost said. “This enzyme can be inhibited by medications that are strong CYP2D6 inhibitors, such as fluoxetine, paroxetine and bupropion.”

According to Frost, it’s likely that millions of Americans may be suffering the ill effects of this drug-to-drug interaction.

“These drugs are super-common,” he said. “They’re all in the top 200 prescription drugs. In addition, chronic pain and depression and anxiety go hand in hand.”

“Many chronic pain patients are taking antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), which many of these CYP2D6 inhibitors fit into. There are a lot of patients who experience both, unfortunately. The likelihood that somebody on one of these offending agents and tramadol is relatively high.”

The good news is that this problem has a relatively easy fix, said Frost.

“We have a lot of other antidepressants available that are in the same class of medication that don’t inhibit this particular enzyme, such as Zoloft (sertraline), (Celexa) citalopram and Lexapro (escitalopram),” he said. “You also have other options for pain control, non-opioid medications such as NSAIDs. If we need to use opioids, a scheduled morphine or a scheduled oxycodone would avoid this interaction.”

“For patients who have the combination of chronic pain and depression or anxiety, keep in mind that this interaction does exist,” Frost said. “And for health care providers, if you have a patient approaching you saying this medication isn’t working for me, is there an interaction at play?”

Source: University Hospitals Cleveland Medical Center