7 Duloxetine Interactions to Know About

Duloxetine (Cymbalta) is an antidepressant. It’s FDA approved to treat depression and anxiety. But duloxetine has uses beyond mental health conditions. It can also treat nerve pain due to diabetes, fibromyalgia, and chronic pain.

Duloxetine is in a class of medications called serotonin and norepinephrine reuptake inhibitors (SNRIs). These medications raise levels of chemicals serotonin and norepinephrine in the brain and nerves. This is thought to improve mood and relieve nerve pain.

Like most medications, duloxetine has the potential to interact with other medications, supplements, and common beverages. Many of these interactions can lead to excess side effects. And in some cases, these side effects could be serious.

Below you’ll find seven of the most common duloxetine interactions and ways to manage them. But keep in mind this isn’t a full list of all possible interactions.

1. Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are medications used to treat depression and Parkinson’s disease. Duloxetine and MAOIs both raise serotonin levels in the brain. Taking them together puts you at risk of a serious side effect called serotonin syndrome.

Serotonin syndrome is a condition caused by too much serotonin in the brain. Some symptoms of serotonin syndrome to watch out for include a fast heart rate, uncontrollable body movements, and sweating. In severe cases, it can be fatal.

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You shouldn’t take MAOIs and duloxetine together. If you’re switching from one medication to the other, you’ll have to wait a certain amount of time between medications. If you’re stopping an MAOI, you’ll have to wait at least 2 weeks between your last MAOI dose and your first duloxetine dose. In turn, you’ll have to wait at least 5 days between your last duloxetine dose and your first MAOI dose.

Tell your healthcare provider if you’re taking an MAOI before starting duloxetine. This will help you avoid a potentially serious interaction.

2. Fluvoxamine

Fluvoxamine (Luvox) is a medication used to treat the symptoms of obsessive-compulsive disorder (OCD). It interacts with duloxetine in two ways.

Fluvoxamine blocks one of the enzymes (proteins) that breaks duloxetine down. This can lead to too much duloxetine in the body. And this raises the risk of side effects like drowsiness, dry mouth, and constipation.

Fluvoxamine helps boost serotonin levels in the brain. So combining it with duloxetine can also raise the risk of serotonin syndrome. While this risk is likely lower than with MAOIs, it’s still possible.

It’s not recommended to take both duloxetine and fluvoxamine. Your healthcare provider would likely pick an alternative for one of these.

3. Other antidepressants

Most antidepressants work by raising serotonin levels. So taking more than one can raise the risk of serotonin syndrome. It’s not recommended to combine duloxetine with other antidepressants.

Other common antidepressants include:

• Selective serotonin reuptake inhibitors (SSRIs) like paroxetine (Paxil, Brisdelle) and fluoxetine (Prozac)

• Other SNRIs like venlafaxine (Effexor XR)

• Tricyclic antidepressants (TCAs) like desipramine (Norpramin) and amitriptyline

• Atypical antidepressants like trazodone

What’s more, some of these antidepressants also interfere with certain enzymes that break down duloxetine. Paroxetine and fluoxetine slow down one of these enzymes. This can raise levels of duloxetine. A different enzyme breaks down both desipramine and duloxetine. Combining these medications causes desipramine levels in the body to rise significantly.

Sometimes it may be necessary to take more than one kind of antidepressant. In this case, your healthcare provider has probably determined that the benefits outweigh the risks for you. They’ve likely also made dose adjustments to help limit side effects. Be sure to report any new or unusual side effects when starting a combination of antidepressants. Further dosage changes may be needed.

4. St. John’s wort

St. John’s wort is an over-the-counter (OTC) herbal supplement. It’s commonly taken for mild to moderate depression symptoms. St. John’s wort raises serotonin levels in the brain. Taking it with duloxetine raises your risk of serotonin syndrome.

It’s not typically recommended to take both St. John’s wort and duloxetine. Make sure your healthcare provider knows if you’re taking St. John’s wort. They may want to make medication changes to avoid this duloxetine interaction.

5. Nonsteroidal anti-inflammatory drugs (NSAIDs)

Duloxetine can raise the risk of bleeding and bruising. This risk is even higher if you’re also taking a nonsteroidal anti-inflammatory (NSAID). NSAIDs help relieve fever, pain, and swelling. And they’re often a go-to for symptoms like headaches and menstrual cramps.

Common OTC and prescription NSAIDs include:

• Aspirin

• Diclofenac (Cambia, Cataflam)

• Ibuprofen (Advil, Motrin)

• Naproxen (Aleve, Naprosyn)

This duloxetine interaction can lead to serious bleeding or stomach ulcers. So it’s best to ask your healthcare provider before taking any NSAIDs with duloxetine. They may suggest a different pain reliever, like acetaminophen (Tylenol), that doesn’t have this risk.

If you get the green light to take NSAIDs and duloxetine, watch for symptoms of serious bleeding. Examples include easier bruising, blood in your urine, and red or black stools. If you notice any of these, contact your provider immediately.

6. Blood thinners

Blood thinners are medications used to treat or prevent unwanted blood clots. They include both anticoagulants and antiplatelet medications. One of their most common side effects is excess bleeding. As mentioned above, duloxetine also carries a risk of bleeding. Taking blood thinners with duloxetine can raise the risk of serious bleeding.

Commonly prescribed blood thinners include:

• Apixaban (Eliquis)

• Clopidogrel (Plavix)

• Rivaroxaban (Xarelto)

• Warfarin (Coumadin, Jantoven)

Taking both duloxetine and a blood thinner isn’t ideal. But some people may need to take both. If this is the case for you, watch for signs of bleeding. Be sure to report any symptoms of bleeding to your healthcare provider. But don’t stop either your blood thinner or duloxetine without their OK to do so.

7. Alcohol

Alcohol and duloxetine don’t mix well together. Alcohol can worsen duloxetine side effects, or make them more likely to happen. But the combination can also raise the risk of liver damage. This is especially true for people who drink heavily over a long period of time.

Symptoms of liver damage include:

• Nausea or vomiting

• Tiredness

• Loss of appetite

• Right-sided stomach pain

• Yellowing of the skin or eyes (jaundice)

• Dark urine

The effects of occasional alcohol consumption on duloxetine isn’t well-studied. Talk to your healthcare provider before drinking any alcohol with this medication. If you regularly drink alcohol, it’s important to be honest with your provider about it. This can help prevent serious problems from combining duloxetine and alcohol.

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

It’s important to share a complete medication list with your healthcare provider and pharmacist. Include all prescription and OTC medications, as well as supplements, you’re taking. It’s also important that you share how much alcohol you drink. Doing so can help you avoid duloxetine interactions. Update your medication list whenever you start a new medication, or make changes to your current ones.

You should also contact your healthcare provider if you think you’re experiencing a duloxetine interaction. Symptoms of an interaction may include new or worsening side effects of a medication. It could also include a return or worsening of symptoms of your health condition. But even if you suspect an interaction, don’t make any medication changes without your provider’s OK.

If you experience any symptoms of serotonin syndrome, severe bleeding, or liver damage, as described above, seek medical help right away. These are serious conditions that can become life threatening. They may require care in a hospital setting.

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Written by:

Kristine Foley, PharmD

Kristine Foley is a licensed pharmacist with over 13 years of community pharmacy experience. She earned her Doctor of Pharmacy degree from Rutgers University.

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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