9 SSRI Interactions: Blood Thinners, Ibuprofen, and More
Key takeaways:
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressant medications. Each SSRI has its own potential interactions. But there are some interactions that are risks with all or most SSRIs.
SSRIs can interact with medications that increase your risk of bleeding. Examples of these medications include blood thinners and nonsteroidal anti-inflammatory drugs (NSAIDs).
SSRIs make more serotonin available in the brain. Because of this, they can interact with other medications that affect serotonin levels, increasing the risk of serotonin syndrome. Examples of these medications include other antidepressants, migraine medications, and St. John’s wort.
Make sure your healthcare team has a list of your current medications and supplements. That way, they can check for potential interactions and make a plan for managing them.
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Table of contents
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that includes medications like fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro). Before starting treatment with an SSRI — and while you’re taking one — it’s good to be aware of potential interactions.
Each SSRI has its own potential interactions. But due to how SSRIs work and affect the body, there are some interactions that are risks with all or most medications in the class. Below are 9 common SSRI interactions that you should know about.
1. Blood thinners
Blood thinners (anticoagulants) are used to treat and prevent blood clots. Examples include warfarin (Coumadin, Jantoven) and apixaban (Eliquis). Bleeding is a common side effect of these medications. And while less common, SSRIs can also increase the risk of bleeding.
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If you take an SSRI with a blood thinner, your risk of bleeding may be higher. So be sure to let your healthcare provider know if you notice signs of minor bleeding, such as bleeding gums or bruising easily. Get immediate medical attention if you have nosebleeds that are difficult to stop, blood in your urine or stool, or bruises covering a large area of your body.
2. NSAIDs like ibuprofen
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin), are available over the counter (OTC) to treat pain. Like SSRIs, NSAIDs can increase your risk of bleeding, and taking them together can increase this risk.
If you’re taking an SSRI, check with your healthcare provider or pharmacist before taking NSAIDs. Occasional NSAID use, such as for a headache, may not be a big deal. But higher doses or long-term use may be more concerning, since the risk of bleeding goes up in these cases.
Even if your healthcare provider says it’s OK for you to take NSAIDs with your SSRI, it’s a good idea to keep an eye out for signs and symptoms of bleeding.
3. Other antidepressants
SSRIs are thought to work by making more serotonin available in your brain. Other medications, including other antidepressant classes, can also have this effect. And this is an issue because too much serotonin in the body can result in a rare but potentially serious condition called serotonin syndrome.
Serotonin syndrome is more likely to occur if you take more than one antidepressant that affects serotonin levels. Examples of medications that have this effect include:
Monoamine oxidase inhibitors (MAOIs), such as selegiline (Emsam, Zelapar)
Tricyclic antidepressants, such as amitriptyline
Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor)
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Certain combinations, such as MAOIs and SSRIs, should be avoided altogether. In fact, you’ll need to wait at least 14 days after stopping treatment with an MAOI before you can start taking an SSRI.
If you’re prescribed an SSRI with another antidepressant, you may be told to watch for symptoms of serotonin syndrome. Examples of these symptoms include sweating, tremors (shaking), and a fast heartbeat. Tell your healthcare provider if you experience any of these symptoms. And if any feel severe or life-threatening, go to the nearest ER.
4. Triptan medications
Triptan medications are used to treat migraine attacks. They work by attaching to serotonin receptors (chemical binding sites) in the brain, which means they can increase your risk of serotonin syndrome.
While uncommon, taking a triptan with an SSRI can lead to serotonin syndrome. Even if you’re not taking a triptan very often, it’s a good idea to monitor yourself for symptoms and tell your healthcare provider if any develop. If needed, your provider can discuss other migraine medication options with you.
5. Dextromethorphan
If you have a cough, you may be tempted to reach for an OTC cough suppressant like dextromethorphan (Delsym). When taken on its own, serotonin syndrome isn’t very likely with dextromethorphan. But this risk goes up if you take it with an SSRI.
If you take an SSRI, talk to your healthcare provider or pharmacist before taking dextromethorphan for cough relief. Keep in mind that dextromethorphan is an ingredient in many combination cough, cold, and flu products, in addition to being available on its own. So be sure to read OTC medication labels carefully.
If your healthcare provider says it’s OK for you to take dextromethorphan with your SSRI, be sure to watch for symptoms of serotonin syndrome. If it’s not OK for you to take dextromethorphan, your provider can suggest alternative cough medications. There are also a few medication-free remedies that you can try.
6. Pain medications like tramadol
In addition to working on opioid receptors, some opioid pain medications also affect serotonin. Tramadol (ConZip, Qdolo), methadone, and fentanyl are a few examples. When taken with SSRIs, these medications increase the risk of serotonin syndrome.
While the risk may vary by medication, all opioids carry a warning about the possibility of serotonin syndrome when combined with medications like SSRIs. Opioids can also cause drowsiness, which may be worsened when taken with SSRIs.
If you’re taking an opioid with an SSRI, tell your healthcare provider if you experience excessive drowsiness or symptoms of serotonin syndrome. And get emergency medical attention if any symptoms feel severe or life-threatening.
Good to know: Some SNRIs, such as duloxetine (Cymbalta), are approved to treat both mental health conditions and certain types of chronic pain. If you’re managing a pain condition long term, an SNRI might be a potential alternative to an SSRI and opioid.
7. St. John’s wort
St. John’s wort is a dietary supplement that’s commonly taken for its antidepressant effects. However, it has a long list of potential interactions, including with SSRIs. In some cases, the interactions are due to the supplement’s effects on serotonin, which can increase the risk of serotonin syndrome.
If you’re taking an SSRI, talk to your healthcare provider before taking St. John’s wort. Due to an increased risk of serotonin syndrome, this combination isn’t recommended.
8. Nausea medications
Some prescription nausea medications carry a warning about serotonin syndrome, which is more likely if they’re taken with medications like SSRIs. Metoclopramide (Reglan) and ondansetron (Zofran) are two examples of medications that carry this warning.
Ondansetron is typically taken to manage short-term nausea, such as nausea after surgery or from chemotherapy. And metoclopramide isn’t usually taken for longer than 12 weeks. If you’ve been prescribed either of these medications with an SSRI, you may be told to watch for symptoms of serotonin syndrome during treatment and to let your provider if any develop.
9. Alcohol
You may be wondering if it’s OK to drink alcohol while taking an SSRI. The short answer is: probably not. Alcohol can slow down your brain function and worsen depression symptoms. It can also worsen SSRI side effects, such as drowsiness, dizziness, and nausea.
Like medication, alcohol affects people differently. So it’s best to discuss your specific situation with your healthcare provider. They can tell you how much alcohol (if any) is safe for you to drink with your SSRI.
When should you contact your healthcare provider about an SSRI interaction?
Before you start taking a new SSRI and during treatment, make sure your healthcare team has your up-to-date medication list, which should also include any OTC products and supplements you take. This way, they can help you prevent or manage potential SSRI interactions before they become a problem.
Your healthcare provider will determine if you can safely take other medications with your SSRI. Certain combinations may need to be avoided. But others may require dosage changes and close monitoring. Keep in mind that your specific SSRI may have other potential interactions that aren’t covered on this list.
Serotonin syndrome is one of the most common issues resulting from SSRI interactions. While serotonin syndrome is rare — and the symptoms are often mild — it can become life-threatening in severe cases. Tell your healthcare provider if you notice symptoms such as sweating, tremors, or a fast heartbeat. And get emergency medical care if you have any symptoms that feel severe or life-threatening.
The bottom line
Selective serotonin reuptake inhibitors (SSRIs) can interact with other medications that affect serotonin, possibly resulting in serotonin syndrome. Examples of these medications include other antidepressants, triptans, and St. John’s wort. Taking an SSRI with blood thinners or NSAIDs can increase your risk of bleeding.
Some medications and substances should be avoided when taking an SSRI. In other cases, dosage changes and monitoring for side effects may be recommended to manage interactions. Talk to your healthcare provider or pharmacist if you have questions about SSRI interactions.
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References
Alam, S. M., et al. (2022). Selective serotonin reuptake inhibitors increase risk of upper gastrointestinal bleeding when used with NSAIDs: A systemic review and meta‑analysis. Scientific Reports.
Bleakley, S. (2016). Antidepressant drug interactions: Evidence and clinical significance. Progress in Neurology and Psychiatry.
De Abajo, F. J. (2011). Effects of selective serotonin reuptake inhibitors on platelet function: Mechanisms, clinical outcomes and implications for use in elderly patients. Drugs & Aging.
U.S. Food and Drug Administration. (2022). FDA Drug Safety Podcast: FDA warns about several safety issues with opioid pain medicines; requires label change.
