---
title: "Psych News Alert: Some Antidepressants May Diminish Pain Control With Tramadol"
description: The effectiveness of tramadol, a frequently prescribed opiate painkiller, may be significantly diminished when patients are also taking c...
image: https://alert.psychnews.org/hubfs/Imported_Blog_Media/rxpad_iStock-669638328_edited-Jun-24-2025-10-36-53-6105-PM.jpg
---

 6/26/19 12:00 AM

# Some Antidepressants May Diminish Pain Control With Tramadol

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The effectiveness of tramadol, a frequently prescribed opiate painkiller, may be significantly diminished when patients are also taking certain, commonly prescribed antidepressants, such as bupropion (Wellbutrin), fluoxetine (Prozac), or paroxetine (Paxil), according to a [study](https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/phar.2269) in *Pharmacotherapy*.

Those, and other, antidepressants inhibit an enzyme known as CYP2D6, which also metabolizes tramadol. The study found that when CYP2D6 is inhibited by an antidepressant, the painkiller becomes less effective, requiring patients to need a short-acting opiate, such as morphine or another painkiller, to control “breakthrough” pain, the acute pain that breaks through the effects of tramadol. (There are five “strong CYP2D6 inhibitors”: bupropion, fluoxetine, paroxetine, terbinafine, and quinidine. Frost and colleagues list 13 other antidepressants as moderate or weak inhibitors.)

“These findings imply that additional considerations may be required for the evaluation of pain management regimens in patients taking one of these [antidepressant] medications, as higher doses or different [pain-control] agents may be required,” wrote Derek A. Frost, Pharm.D., of University Hospitals Portage Medical Center, Ravenna, Ohio, and colleagues.

They assessed 152 hospitalized patients prescribed tramadol for chronic pain. Of these, 76 were also taking one of the strong CYP2D6-inhibiting antidepressants. The primary outcome measure was the amount of breakthrough opiate required by patients.

Patients receiving one of the antidepressants and tramadol required a higher per-day average of breakthrough opiate (18.2 mg) than those in the control group (5.7 mg) and required more total breakthrough opiate overall (42.4 mg vs 10.2 mg).

“This study supports the use of a tramadol alternative for pain management in patients taking a strong CYP2D6 inhibitor,” the authors wrote. “It would also benefit each patient to assess the response to their depression treatment when a pain management regimen is being considered. Patients who are nonresponsive to treatment while taking a strong CYP2D6 inhibitor may be switched to an appropriate alternative regimen for managing their depression.”

For related information see the *Psychiatric News* article, “[NIDA Director Outlines Institute’s Efforts to Understand Pain, Reduce Opioid Misuse](https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2019.6b39).”

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[antidepressants](https://alert.psychnews.org/tag/antidepressants), [opioids](https://alert.psychnews.org/tag/opioids), [bupropion](https://alert.psychnews.org/tag/bupropion), [terbinafine](https://alert.psychnews.org/tag/terbinafine), [quinidine](https://alert.psychnews.org/tag/quinidine), [tramadol](https://alert.psychnews.org/tag/tramadol), [CYP2D6](https://alert.psychnews.org/tag/cyp2d6), [paroxetine](https://alert.psychnews.org/tag/paroxetine), [fluoxetine](https://alert.psychnews.org/tag/fluoxetine), [pain control](https://alert.psychnews.org/tag/pain-control)

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