9 SNRI Interactions: Stimulants, Ibuprofen, and More
Key takeaways:
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a commonly prescribed class of antidepressant medications. They work by making more norepinephrine and serotonin available in the brain.
SNRIs can increase your risk of bleeding, especially if they’re taken with blood thinners. They can also increase your blood pressure, which may be worsened when taken with stimulants.
SNRIs can interact with other medications that affect serotonin. Examples include triptans, pain medications, and other antidepressants. Taking these medications with SNRIs can increase your risk of serotonin syndrome.
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Table of contents
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a group of antidepressant medications. Common examples include venlafaxine (Effexor XR), duloxetine (Cymbalta), and desvenlafaxine (Pristiq). SNRIs are thought to work by making more serotonin and norepinephrine available in your brain.
SNRIs have a number of potential interactions. While many of these can be managed in advance by your healthcare team, it's a good idea to be aware of substances that could cause an issue while you're taking an SNRI. This can even include over-the-counter (OTC) products in your medicine cabinet.
Each SNRI has its own unique potential interactions. But there are some interactions that apply to them all. Below, we look at nine SNRI interactions that you should be aware of and how to avoid potential issues.
Other antidepressants
SNRIs can interact with other medications that affect serotonin. This can increase your risk of serotonin syndrome. Serotonin syndrome is a rare but potentially life-threatening condition caused by too much serotonin in the body.
Examples of antidepressant classes that can affect serotonin include:
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac)
Tricyclic antidepressants, such as clomipramine (Anafranil)
Monoamine oxidase inhibitors (MAOIs), such as selegiline (Emsam, Zelapar)
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It’s recommended to avoid taking an SNRI and an MAOI together. This combination has a significantly higher risk of serotonin syndrome than others.
Other antidepressants may be OK to take with an SNRI. But you could be instructed to watch for symptoms of serotonin syndrome. These symptoms include sweating, shaking (tremors), and a fast heartbeat. In severe cases, hallucinations, seizures, and loss of consciousness are also possible.
If you think you might be experiencing serotonin syndrome, tell your prescriber right away. If your symptoms feel severe or life-threatening, however, you should go to the nearest ER.
1. Blood thinners
Anticoagulants and antiplatelets (blood thinners) are medications used to prevent or treat blood clots. Examples include warfarin (Coumadin), apixaban (Eliquis), and clopidogrel (Plavix). These medications work by thinning your blood, so they can increase your risk of bleeding.
Due to their effects on platelets, SNRIs can also increase your risk of bleeding. And taking an SNRI with a blood thinner can further increase this risk. So tell your prescriber if you notice signs or symptoms of bleeding if you’re taking this combination.
Symptoms of minor bleeding include bleeding gums and bruising more than usual. Symptoms of severe bleeding, which is also possible, include nosebleeds that don’t stop, bloody urine or stool, and large areas of bruising on your body. Get immediate medication attention if you experience any of these.
2. NSAIDs like ibuprofen
Nonsteroidal anti-inflammatory drugs (NSAIDs) are popular OTC pain relievers. Examples include ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn). NSAIDs can also affect your platelets and increase your risk of bleeding. Taking an NSAID with an SNRI can raise this risk even more.
If you’re taking an SNRI, it’s best to talk to your prescriber before taking an NSAID, especially taking one frequently. And let them know if you notice signs or symptoms of bleeding with this combination.
3. Blood pressure medications
Due to their effects on norepinephrine, SNRIs can increase blood pressure as a side effect. If you’re taking medication to lower your blood pressure, it may not work as well with an SNRI.
Blood pressure changes related to SNRIs are usually small. But they can be more significant for some people. If you have high blood pressure, your prescriber may keep a closer eye on your readings and make adjustments to your medication regimen as needed. They may recommend taking an SSRI instead of your SNRI, for example. SSRIs haven’t been found to affect blood pressure.
4. Stimulants
As a category, stimulants include a wide variety of medications and substances. There are prescription-only stimulants that are taken for attention deficit-hyperactivity disorder (ADHD), narcolepsy, and weight loss. Other stimulants, such as caffeine, can be found in foods and beverages. OTC decongestants like pseudoephedrine (Sudafed) can also have stimulant effects.
Stimulants constrict (tighten) blood vessels throughout the body, which can cause an increase in blood pressure. As mentioned above, SNRIs can also raise blood pressure, an effect which may be more significant if they’re taken with a stimulant. Stimulants may also worsen insomnia, another possible side effect of SNRIs.
What’s more, some stimulants can affect serotonin. This can increase the risk of serotonin syndrome if they’re taken with an SNRI. Examples of stimulants that can have this effect include amphetamine salts (Adderall) and phentermine (Adipex-P).
It’s best to discuss the specifics of combining an SNRI and stimulant with your prescriber. If they say it’s OK for you to take this combination, they may want to closely monitor your blood pressure and have you watch for serotonin syndrome. If needed, they may advise you on non-stimulant alternatives.
5. Triptan medications
Triptans are a class of medications used to treat migraine attacks. They help relieve migraine pain by attaching to serotonin receptors (chemical binding sites). These receptors are located in your brain and throughout your body.
Taking an SNRI and triptan together can increase your risk of serotonin syndrome. Triptans are only taken as needed for migraines, so the risk of serotonin syndrome tends to be low. But it’s still possible. Your prescriber may discuss alternative migraine medications that don’t affect serotonin with you, if you’re taking an SNRI.
Contact your prescriber right away if you think you’re experiencing serotonin syndrome. They may have you manage mild symptoms at home. But some cases require immediate medical care.
6. Pain medications like tramadol
Opioid pain medications — such as tramadol (ConZip, Qdolo), oxycodone (Roxicodone), and fentanyl — carry a warning about there being a possibility of serotonin syndrome when they’re taken with medications like SNRIs.
SNRIs also have a few shared potential side effects with opioids. Examples include nausea and constipation, side effects which may be worse if you take an SNRI and opioid together.
Talk to your prescriber about ways to manage potential interactions between opioids and SNRIs. They’ll likely have you watch for serotonin syndrome and any new or worsening side effects if you take this combination. If needed, they may talk to you about alternative, non-opioid pain relievers.
7. Alcohol
Can you drink alcohol while taking an SNRI? The short answer: It’s best to avoid this combination. Consuming alcohol can slow down how your brain functions and even worsen your depression symptoms. Alcohol may also increase the risk of liver damage when combined with certain SNRIs, such as duloxetine.
Everyone responds to medications and alcohol differently. So it’s best to talk to your healthcare team about your specific situation. They can also discuss ways for you to safely reduce or stop drinking alcohol.
8. St. John’s wort
Some people may take St. John's wort to treat their depression symptoms. But it has a number of potential interactions, some of which can be dangerous. That’s why it’s a good idea to check with your healthcare team before taking St. John’s wort.
When it’s taken with an SNRI, St. John’s wort can increase the risk of serotonin syndrome. Because of this, it’s generally recommended to avoid this combination.
If your current antidepressant isn’t working for you, talk to your prescriber. They can also talk with you about safer medication-free ways to help manage your symptoms.
9. When should you contact your prescriber about an SNRI interaction?
The best way to avoid serious problems from an interaction is to be proactive. Ensure that your healthcare team has your current medication and supplement list. They can work with you to avoid or manage potential SNRI interactions before they happen. This means updating them on any medication changes while you’re taking an SNRI, too.
Your prescriber will decide if you can safely take a potentially interacting medication with an SNRI. Keep in mind that each SNRI has unique interactions, in addition to those listed above. Some interactions should be avoided completely. Others may require a lower dosage or monitoring for potential side effects.
Speak with your prescriber if you experience any new or unusual symptoms while taking an SNRI. And get immediate medical attention if you have any symptoms that feel severe or life-threatening.
The bottom line
Potential serotonin and norepinephrine reuptake inhibitor (SNRI) interactions include interactions with medications that affect serotonin, blood thinners, and nonsteroidal anti-inflammatory drugs (NSAIDs). SNRIs can also interact with stimulants, blood pressure medications, and St. John’s wort.
Some SNRI interactions can be managed with close monitoring for side effects. Others may need to be avoided altogether. Speak with your healthcare team if you have questions about SNRI interactions.
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References
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Edinoff, A. N., et al. (2022). Selective serotonin reuptake inhibitors and associated bleeding risks: A narrative and clinical review. Health Psychology Research.
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