Vilazodone Drug Interactions You Need to Know About

Vilazodone (brand name Viibryd) is an effective antidepressant, but like any medication, it can interact with other drugs, supplements, and even certain foods. Some of these interactions are dangerous — others just require a dose adjustment. Either way, you need to know about them before you start taking Vilazodone.

This guide covers the major and moderate drug interactions, supplements and OTC products to watch out for, and what information you should share with your doctor.

How Drug Interactions Work

Drug interactions happen when one substance changes how another substance works in your body. With Vilazodone, interactions fall into two main categories:

• Serotonin-related interactions — Vilazodone increases serotonin levels in the brain. Combining it with other substances that also boost serotonin can lead to dangerously high levels, causing a condition called serotonin syndrome.
• Metabolism-related interactions — Vilazodone is broken down in the liver by an enzyme called CYP3A4. Drugs that speed up or slow down this enzyme can change how much Vilazodone ends up in your bloodstream.

Understanding these two pathways will help you make sense of the specific interactions listed below.

Medications That Interact with Vilazodone

Major Interactions (Avoid or Use Extreme Caution)

These combinations are potentially dangerous and should generally be avoided:

• MAO Inhibitors — Isocarboxazid (Marplan), Phenelzine (Nardil), Tranylcypromine (Parnate), and Selegiline (Emsam patch). Combining these with Vilazodone can cause life-threatening serotonin syndrome. You must wait at least 14 days after stopping an MAO inhibitor before starting Vilazodone, and at least 14 days after stopping Vilazodone before starting an MAO inhibitor.
• Linezolid (Zyvox) — This antibiotic has MAO-inhibiting properties and can trigger serotonin syndrome when combined with Vilazodone.
• IV Methylene Blue — Used for certain medical conditions, intravenous methylene blue also has MAO-inhibiting effects and should not be used with Vilazodone.
• Other serotonergic drugs — Combining Vilazodone with other medications that increase serotonin raises the risk of serotonin syndrome. These include:
  • Other antidepressants — SSRIs (Sertraline, Fluoxetine, Escitalopram), SNRIs (Duloxetine, Venlafaxine), tricyclics (Amitriptyline, Nortriptyline)
  • Triptans for migraines — Sumatriptan (Imitrex), Rizatriptan (Maxalt), Zolmitriptan (Zomig)
  • Tramadol (Ultram) — A pain medication with serotonergic activity
  • Fentanyl — Including the Fentanyl patch (Duragesic)
  • Lithium — Used for bipolar disorder
  • Buspirone (Buspar) — An anti-anxiety medication
• Strong CYP3A4 inhibitors — Ketoconazole (Nizoral), Itraconazole (Sporanox), Clarithromycin (Biaxin), and similar drugs slow down the enzyme that breaks down Vilazodone. This means more Vilazodone builds up in your system, increasing side effects. If you must take a strong CYP3A4 inhibitor, your Vilazodone dose should be reduced to 20 mg daily.
• Strong CYP3A4 inducers — Carbamazepine (Tegretol), Rifampin (Rifadin), Phenytoin (Dilantin), and St. John's Wort speed up Vilazodone's breakdown, potentially making it less effective. Your doctor may need to increase the Vilazodone dose (up to 80 mg daily) if you're taking one of these.

Moderate Interactions (Use with Caution)

These combinations require monitoring but aren't necessarily prohibited:

• Anticoagulants — Warfarin (Coumadin) combined with Vilazodone may increase bleeding risk. Your doctor may need to monitor your INR more frequently.
• NSAIDs and Aspirin — Ibuprofen (Advil, Motrin), Naproxen (Aleve), and Aspirin can increase the risk of abnormal bleeding when taken with Vilazodone. This doesn't mean you can't use them, but be aware of unusual bruising, nosebleeds, or blood in your stool.
• Diuretics — Water pills like Hydrochlorothiazide and Furosemide (Lasix) may increase the risk of hyponatremia (low sodium) when combined with Vilazodone. This is especially important for elderly patients.
• Other CNS depressants — Benzodiazepines (Alprazolam, Lorazepam), sleep medications, and other sedatives may cause enhanced drowsiness when combined with Vilazodone.

Supplements and OTC Products to Watch

It's not just prescription drugs that can interact with Vilazodone. Be careful with these over-the-counter products and supplements:

• St. John's Wort — This herbal supplement is widely used for mild depression, but it increases serotonin levels and speeds up Vilazodone's metabolism. This creates a double problem: higher serotonin syndrome risk and reduced Vilazodone effectiveness. Do not take St. John's Wort with Vilazodone.
• Tryptophan supplements — L-Tryptophan and 5-HTP are serotonin precursors that can increase serotonin levels when combined with Vilazodone.
• NSAIDs — Over-the-counter Ibuprofen (Advil, Motrin) and Naproxen (Aleve) increase bleeding risk with Vilazodone. Occasional use may be fine, but discuss regular use with your doctor.
• Aspirin — Even low-dose Aspirin for heart health can increase bleeding risk with Vilazodone.

Food and Drink Interactions

Two food-related interactions to know about:

• Food (required) — Vilazodone must be taken with food. This isn't really an "interaction" — it's a requirement. Absorption drops by up to 50% on an empty stomach, which means you'd only be getting half the dose. Take Vilazodone with a full meal or substantial snack every time.
• Alcohol — Alcohol can worsen the central nervous system side effects of Vilazodone, including dizziness, drowsiness, and impaired concentration. While there's no absolute ban, most doctors recommend limiting alcohol intake while taking Vilazodone, especially when you're first starting the medication.

What to Tell Your Doctor

Before starting Vilazodone, make sure your doctor knows about:

• All prescription medications — Including any you've recently stopped. MAO inhibitors, for example, require a 14-day washout period.
• All over-the-counter medications — Especially pain relievers (Ibuprofen, Naproxen, Aspirin) and cold/cough medicines that may contain Dextromethorphan (a serotonergic drug found in many OTC cough syrups).
• All supplements and herbal products — Especially St. John's Wort, Tryptophan, 5-HTP, and SAMe.
• Migraine medications — Triptans interact with Vilazodone.
• Recent or upcoming procedures — If you might receive IV Methylene Blue or Linezolid during a procedure or hospitalization.
• Alcohol use — Be honest about how much you drink.

Don't assume your doctor knows about every supplement or OTC product you're taking. It's worth making a complete list and bringing it to your appointment. For help finding a doctor who can prescribe and monitor Vilazodone, see our prescriber guide.

Final Thoughts

Vilazodone is generally safe when used as directed, but its interactions — particularly serotonin-related ones — are serious. The most important thing you can do is be transparent with your healthcare provider about everything you're taking. This includes prescription drugs, OTC medications, herbal supplements, and alcohol.

If you're concerned about a specific interaction, don't stop taking Vilazodone on your own — call your doctor or pharmacist first. And if you need help finding Vilazodone at a pharmacy near you, Medfinder can help.