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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Written By Eric Christianson

January 27, 2021

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