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Opioid analgesics

Efficacy of tramadol reduced by concurrent use of some antidepressants

Research has shown that patients taking tramadol while also on an antidepressant, such as fluoxetine, received significantly more breakthrough opioid therapy to maintain similar pain scores, compared with patients who were not on an antidepressant.

Tramadol pills in blister pack


Patients taking certain antidepressants received significantly more breakthrough opioid therapy to achieve similar pain scores, compared with control patients

Certain antidepressants reduce the efficacy of the opioid medicine tramadol, according to research published in Pharmacotherapy (30 April 2019)[1].

Researchers looked at the records of 152 adult inpatients who received scheduled tramadol for at least 24 hours, half of whom were also receiving an antidepressant, such as fluoxetine, paroxetine or bupropion, which are characterised as strong cytochrome P450 (CYP) 2D6 inhibitors. 

They found that patients on the antidepressants received significantly more breakthrough opioid therapy to maintain similar pain scores when compared with patients not taking antidepressants, at a mean of 18.2 morphine milligram equivalents (MME) versus 5.7 MME per day. This was despite no significant difference in mean pain scores between the two groups.

The analgesic effect of tramadol is dependent on metabolism via CYP2D6, which is strongly inhibited by some antidepressants. The researchers said the results indicated that medication reviews should consider this interaction, which can easily be avoided with alternative antidepressants or pain medicines.

“This study supports the use of a tramadol alternative for pain management in patients taking a strong CYP2D6 inhibitor,” the authors wrote. “Patients who are nonresponsive to [depression] treatment while taking a strong CYP2D6 inhibitor may be switched to an appropriate alternative regimen for managing their depression,” they add. 

Citation: The Pharmaceutical Journal DOI: 10.1211/CP.2019.20206865

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