SSRIs and CYP Enzymes

SSRIs and CYP enzymes

While many who don’t understand pharmacology consider the SSRIs to be interchangeable, significant consequences can result if we don’t pay attention to the risk of drug interactions. When looking at the SSRIs and CYP enzymes, it is critical to remember which ones can interact with other medications. There is also a significant potential that it will show up on board exams 🙂

Here’s a brief summary on some of the most important SSRIs and CYP enzymes.


Remember that fluvoxamine interacts with everything. This is what I do at least. CYP3A4, 1A2, 2C9, and 2C19 interactions are all possible with fluvoxamine which is why I typically run a drug interactions checker whenever a patient is taking it. Here’s a classic case scenario of how fluvoxamine can interact with other medications and also some other examples.

Citalopram and Escitalopram

The one interaction that I see most commonly in practice with citalopram is with omeprazole. Any drug that inhibits CYP2C19 can increase the concentrations of citalopram and with it increase the risk for QTc prolongation. Escitalopram carries the same risk. I talk in much greater detail about QTc prolongation in this podcast episode on citalopram.


Sertraline tends to have less significant CYP drug interactions than some of the others. CYP2D6 breaks down sertraline in part and there may also be some 2C19 breakdown. I would say that the significance of another drug inhibiting CYP2D6 or 2C19 on sertraline is probably low. If the patient is on an abnormally high dose of a CYP2D6/2C19 inhibitor or sertraline, then maybe the interaction would have a little more significance.

Paroxetine and Fluoxetine

Paroxetine is a CYP2D6 inhibitor. This can lead to increases in the concentrations of drugs that are broken down by this enzyme. Some of the antipsychotics are broken down by CYP2D6 and concentrations of the antipsychotic can be increased by using paroxetine in combination. Risperidone and aripiprazole are two of the more common examples. In addition, paroxetine can prevent a prodrug from being activated. You MUST know this example.

I always remember that the most sedating (paroxetine) and the most activating (fluoxetine) inhibit the same CYP enzyme. This helps me remember that both paroxetine and fluoxetine inhibit CYP2D6.

There you have, my quick breakdown of the SSRIs and CYP enzymes. Feel free to leave a comment below if you’ve seen an interaction of have something more to add!

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  1. Susan Hofmann


    I am in a post Master’s DNP program and returning to the workforce within a year. I am updating my skill set and studying for boards too. What is a good review book for pharmacology for NP’s? What application do you use as drug check when patients present with their lists? Thanks
    I appreciate your site. Susan Hofmann

    • Eric Christianson

      Hi Susan, thanks for the message! I would say that my best review on pharmacology would be NAPLEX Nuggets (2021 is the latest version). I do have mechanisms of action laid out in that book. As far as a drug application checklist, I mostly utilize uptodate/lexicomp for my drug interaction screens. That is a paid service, but it one of the better ones in my opinion. Thanks and sorry for the delay on this question! Eric


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Written By Eric Christianson

January 27, 2021

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