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Antidepressants can make pain medications less effective

Writer's picture: Dr. Melissa TurnerDr. Melissa Turner

Updated: Apr 25, 2023


Did you know that certain pain medications (codeine, oxycodone, tramadol) must be activated by an enzyme called CYP2D6 in order to work?


However, some antidepressants (bupropion, duloxetine, fluoxetine, paroxetine) can interfere with that enzyme and can cause it not to work. Therefore, the pain medicines that need the CYP2D6 enzyme to be activated, may now be less effective because of the antidepressant and you may not get the pain relief that you need.


If your doctor or the pharmacist who fills your prescription doesn't recognize this interaction, life threatening events could occur.


If you don't know about this interaction, you may choose to take more of the pain medication, thinking that if you take more of it, it will work. However, this can be dangerous too.


Variations in your DNA can also affect how well your CYP2D6 enzyme works. If the pain medication you are taking needs the CYP2D6 enzyme to work but your genetics cause the enzyme to work too fast, you could be at risk of overdose with the pain medication. If your genetics cause the enzyme to work too slow, you're at risk of the pain medication not working at all.


At Tarheel PGx Consulting, we're here to help you learn how all of your medications work together and how they may be affected by your DNA through the use of pharmacogenomic testing.


Click the button below to book a call with our pharmacist and learn more about our services.




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