7 Paroxetine Interactions to Watch For

If you or a loved one lives with depression or anxiety, you may have heard of paroxetine (Paxil, Brisdelle). Paroxetine is an antidepressant that’s been FDA-approved since 1992. It’s unique from other antidepressants because it’s also approved to treat hot flashes related to menopause.

Regardless of why you’re taking paroxetine, it’s important to understand possible interactions when starting it. Paroxetine can interact with many medications. Fortunately, most can be avoided or managed upfront by your healthcare provider. So it’s important to show them your current medication list. This can help your provider spot and manage interactions.

Here are seven important paroxetine interactions you should be aware of. But, keep in mind this list doesn’t include all the interactions that exist.

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1. Monoamine oxidase inhibitors

Medications like selegiline (Zelapar, Emsam) and rasagiline (Azilect) are monoamine oxidase inhibitors (MAOIs). Both MAOIs and paroxetine work by boosting serotonin levels. Serotonin is a chemical messenger in the body that affects many functions, including sleep, bowel movements, and mood.

When MAOIs are taken with paroxetine, the combination raises the risk of serotonin syndrome. Serotonin syndrome is a possibly life-threatening condition caused by too much serotonin in the body.

Serotonin syndrome is rare. But if it happens, it can have serious effects. Severe symptoms include high fever, severe agitation, and rigid muscles. You should get immediate medical care if you have any of these symptoms.

Paroxetine shouldn’t be taken if you’re taking an MAOI. If you’re switching between them, your healthcare provider will likely ask you to stop one for at least 14 days before starting the other to avoid this interaction.

2. Other medications that raise serotonin levels

Selective serotonin reuptake inhibitors (SSRIs), like paroxetine, work by raising serotonin levels. But there are many other medications that can also raise serotonin (called serotonergic medications). Taking paroxetine with other serotonergic medications raises the risk of serotonin syndrome. The risk is lower than it is with MAOIs. But it’s still possible.

Examples of serotonergic medications include:

• Other SSRIs like sertraline (Zoloft)

• Serotonin and norepinephrine reuptake inhibitors (SNRIs), like venlafaxine (Effexor XR)

• Tricyclic antidepressants (TCAs), like amitriptyline

• Other antidepressants like buspirone

• Triptan migraine medications, like sumatriptan (Imitrex)

• Some opioids, like tramadol (Ultram)

Healthcare providers may still prescribe paroxetine and one of these medications despite this interaction. In this case, they may just have you watch for symptoms of serotonin syndrome. But they may also prefer to prescribe an alternative. Talk to your healthcare provider to see which option is better for your situation.

3. St. John’s wort

You may have heard of the dietary supplement St. John’s wort. It’s been studied for treating depression but isn’t FDA-approved for this purpose.

Even though it’s sold over the counter (OTC), St. John’s wort interacts with many medications. It can change how the liver breaks down medications. And it also raises serotonin levels. Taking St. John’s wort with paroxetine also raises the risk of serotonin syndrome.

Be sure your healthcare provider knows if you’re taking St. John’s wort. It’s recommended to avoid combining it with paroxetine unless your provider tells you to. This might mean you need to stop St. John’s wort. Or, your healthcare provider may suggest an alternative to paroxetine.

4. Blood thinners

Blood thinners, such as antiplatelet and anticoagulant medications, treat and prevent blood clots. The main side effect of these medications is a higher risk of bleeding. Paroxetine may also raise the risk of bleeding. So, combining paroxetine with blood thinners can make this risk even greater.

Examples of blood thinners that can interact with paroxetine include:

• Warfarin (Coumadin, Jantoven)

• Rivaroxaban (Xarelto)

• Apixaban (Eliquis)

• Clopidogrel (Plavix)

If you’re already taking a blood thinner, your healthcare provider may suggest an alternative for paroxetine. If you need to take paroxetine, be aware of symptoms of bleeding. This could include excessive bruising, nosebleeds, or bleeding gums. You could also have blood in your urine or stool.

It’s important not to stop either your blood thinner or paroxetine without your healthcare provider’s OK. If you’ve noticed signs of bleeding, contact your provider right away to discuss next steps.

5. Thioridazine and pimozide

Paroxetine affects how a certain liver enzyme (protein) works. This enzyme is called CYP2D6. Other medications that are broken down by this enzyme reach higher levels in the body when combined with paroxetine. This raises the risk of side effects with these other medications.

Two notable examples are thioridazine and pimozide. These are two typical antipsychotics. You shouldn’t take paroxetine if you take thioridazine or pimozide. Paroxetine greatly raises the levels of these two antipsychotics. And high levels of these medications can cause life-threatening heart problems.

Thioridazine and pimozide can cause a prolonged QT interval. The QT interval is the time when your heart is resetting during a heart beat. If the QT interval is too long, it can cause abnormal heart rhythms. When thioridazine or pimozide are combined with paroxetine, the risk of this serious side effect is even greater.

Your healthcare provider will likely recommend a different antidepressant if you take thioridazine or pimozide.

6. Medications broken down by certain liver enzymes

Other medications are also broken down by CYP2D6. Taking them with paroxetine can raise the risk of side effects. But they tend to be less severe than with thioridazine and pimozide.

Examples of other medications broken down by CYP2D6 include:

• Propafenone (Rythmol)

• Flecainide

• Atomoxetine (Strattera)

• Metoprolol (Lopressor, Toprol XL)

• Tolterodine (Detrol)

• Venlafaxine (Effexor XR)

• Risperidone (Risperdal)

This isn’t a complete list. Your pharmacist can tell you if you take other medications that have this paroxetine interaction. If you’re taking one of these medications, you may need a lower dose of them when taking paroxetine. Your healthcare provider will help you figure out whether you need any dosage adjustments.

7. Tamoxifen

Tamoxifen (Nolvadex, Soltamox) is a medication used to prevent and treat certain types of breast cancer.

Tamoxifen is activated by the liver enzyme CYP2D6. When taken with paroxetine, the antidepressant may stop it from changing into its active form. This could make tamoxifen less effective. But more research is needed to confirm the extent of this paroxetine interaction.

Hot flashes are a common side effect of many breast cancer treatments. And paroxetine is a possible hot flash treatment that may be considered. But because of this interaction, your healthcare provider may avoid prescribing both paroxetine and tamoxifen.

When should I contact my healthcare provider about a paroxetine interaction?

If you’re ever concerned about paroxetine interactions, it’s best to check with your healthcare provider. Even though they’re likely aware of possible interactions, it doesn’t hurt to double check.

If there’s a paroxetine interaction, it doesn’t always mean you need a medication change. In some cases, you may just need extra monitoring. But in other cases, you may need a medication or dose change.

If you notice severe symptoms like unusual bleeding or heart palpitations, let your healthcare provider know right away. This could mean you have a serious interaction.

Remember to show your healthcare provider and pharmacist your current medication list before starting paroxetine. Be sure to include all prescription and OTC medications, as well as vitamins and supplements. They can use this list to help spot and manage paroxetine interactions.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

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