Common Antidepressants Interact With Tramadol to Lessen Pain Relief

Common antidepressants interact with tramadol to make it less effective for pain relief, according to a study published in Pharmacotherapy.

The findings have important implications for the opioid epidemic, suggesting that some patients suspected of drug-seeking may in fact be under-medicated and just are seeking more effective pain relief. The results of the study could also help explain why some people exceed the prescribed dose of tramadol, increasing their risk of addiction.

To arrive at their findings, Derek A. Frost, University Hospitals Cleveland Medical Center, Cleveland, Ohio, and colleagues reviewed the medical records of 152 patients who received scheduled tramadol for at least 24 hours. All participants in the study were admitted as inpatients or observation status.

The researchers found that patients who received scheduled tramadol who were also taking fluoxetine (Prozac), paroxetine (Paxil) or bupropion (Wellbutrin) required 3 times more pain medication per day to control breakthrough pain throughout the day, when compared with patients not taking those antidepressants.

“As we looked at in secondary analysis, it ended up being 4 times as much over their entire hospital stay,” said Frost.

Previous studies with healthy volunteers have shown effects on blood levels when combining tramadol with these particular antidepressants. However, this is the first study 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.

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

“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 sertraline, citalopram, and 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.”