7 Auvelity Interactions You Should Know About

If you or a loved one are living with depression, a selective serotonin reuptake inhibitor (SSRI) antidepressant like sertraline (Zoloft) may be in your medicine cabinet. SSRIs are first-choice medications for depression, but they’re not ideal for everyone — especially if you’re looking for fast relief. It can take up to 4 to 8 weeks before you see their full benefits.

It’s understandable to want or need relief in a shorter amount of time. A new prescription-only antidepressant, Auvelity (dextromethorphan/bupropion), offers faster-acting relief than traditional antidepressants. Studies report this oral tablet can start working in as little as 1 week.

Auvelity works by combining two medications — dextromethorphan and bupropion — into one pill. These ingredients work together to elevate mood, but they each have their own set of interactions to be aware of. Your healthcare provider and pharmacist can help you watch for interactions, but it’s important to keep seven of the top ones in mind.

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1. Medications that affect serotonin levels

Auvelity can raise serotonin levels. If you take other medications that also raise serotonin, there’s a chance your serotonin levels could jump too high. In some cases, this could lead to serotonin syndrome.

Thankfully, when it happens, most cases of serotonin syndrome are mild. Possible symptoms include:

• Sweating

• Fast heart rate

• Trouble sleeping (insomnia)

• Tremor (shaking)

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In other cases, serotonin syndrome can cause more serious problems. If you suddenly start experiencing one or more of these symptoms, get medical help right away:

• Confusion

• Agitation

• High blood pressure

• High body temperature

• Hallucinations

• Seizures

Due to risks like these, you shouldn’t combine Auvelity with other medications that raise serotonin levels. One example is a group of medications called monoamine oxidase inhibitors (MAOIs). You should separate doses of MAOIs like selegiline (Zelapar, Emsam) and Auvelity by at least 2 weeks.

Other common medications that can raise serotonin levels include triptan migraine medications, SSRIs like sertraline, and tricyclic antidepressants (TCAs) like imipramine (Tofranil).

2. Medications that interfere with Auvelity’s breakdown

Auvelity is broken down by two main proteins (enzymes) made by the liver. They’re called CYP2B6 and CYP2D6, and they can mean double trouble for interactions. Depending on the situation, medications that mess with these proteins can make Auvelity more or less active.

Several medications can make Auvelity last for longer in your body, raising the risk for side effects. Your healthcare provider may need to lower your Auvelity dose if you take one or more of these medications:

• Clopidogrel (Plavix)

• Fluoxetine (Prozac)

• Paroxetine (Paxil)

• Mirabegron (Myrbetriq)

Other medications, like phenobarbital, have the opposite effect. They can lower Auvelity levels in the body and make it less effective. You should avoid taking phenobarbital with Auvelity.

3. Medications that Auvelity interferes with

Interactions are a two-way street. By interfering with the same proteins mentioned above, Auvelity can also make other medications more or less active. For instance, Auvelity may raise levels of metoprolol (Lopressor, Toprol XL) in your body. This can worsen metoprolol’s side effects.

In addition to metoprolol, Auvelity can affect the usefulness or tolerability of these medications:

• Atomoxetine (Strattera)

• Nebivolol (Bystolic)

• Propranolol (Inderal)

• Amitriptyline

• Nortriptyline (Pamelor)

• Perphenazine

• Venlafaxine (Effexor)

• Propafenone (Rythmol)

• Tolterodine (Detrol)

If you take one or more of the medications listed above, make sure your healthcare provider and pharmacist know about them. They may need to slightly adjust your medication doses.

4. Medications that affect the seizure threshold

Some medications can lower your “seizure threshold.” This means they make it more likely to experience a seizure. Bupropion, an ingredient in Auvelity, is a key example. And when it’s taken with other medications that can also lower the seizure threshold, the risk goes up even more.

Examples of other medications that can lower the seizure threshold include:

• Antipsychotic medications like clozapine (Clozaril)

• Opioids like tramadol (Ultram)

• TCAs like imipramine

• Carbamazepine (Tegretol)

It’s important to be cautious if you take any of these medications with Auvelity. But, you shouldn’t make any sudden changes to your medication routine. Suddenly stopping these medications could also cause seizures. If needed, your healthcare provider can gradually help you lower your doses over time.

5. Dopamine-affecting medications

Auvelity can raise dopamine levels in the brain. Medications like carbidopa/levodopa (Sinemet) and amantadine (Gocovri, Osmolex ER) can also do this. Carbidopa/levodopa and amantadine both treat Parkinson’s disease symptoms.

Similar to having too much serotonin, it’s not ideal to have too much dopamine. Too much dopamine can have negative effects on your central nervous system (brain and spinal cord). Side effects may include tremor, dizziness, and agitation.

Immediate changes to your medication routine may not be necessary if you’re taking this combination. But, your healthcare provider will typically keep an eye on you for side effects.

6. Digoxin

Digoxin (Lanoxin) treats heart failure symptoms and an uncontrolled heart rate. It’s also known as a “narrow therapeutic index” medication. This means that small changes in your digoxin levels can make a big difference in how well it works or how it’s tolerated.

Unfortunately, Auvelity can lower digoxin levels in the body. This can make digoxin not work as well and lead to an undertreated heart condition. If you’re taking Auvelity and digoxin together, your healthcare provider may check your digoxin levels more often.

7. Alcohol

You may be wondering whether it’s safe to have an alcoholic beverage while you’re taking Auvelity. The short answer: it’s best to avoid it. The combination can raise the risk of side effects like dizziness, drowsiness, and confusion. Alcohol can also worsen depression symptoms.

But if you drink large or frequent amounts of alcohol, suddenly stopping alcohol intake can be risky, too. A sudden halt can raise the risk of seizures.

Since Auvelity can also cause seizures, this could be a dangerous combination. Make sure to talk to your healthcare provider about your personal risks of combining alcohol and Auvelity.

When should I contact my healthcare provider about an Auvelity interaction?

Reach out to your healthcare provider or pharmacist if you’re concerned about Auvelity interactions at any point.

Maintaining and sharing an updated list of your over-the-counter and prescription medications can help your pharmacist and healthcare provider screen for interactions from the beginning. If you’re experiencing any side effects, they can check if it’s from an interaction.

What’s more, some side effects need medical intervention. If you experience any symptoms of serotonin syndrome or seizures, reach out to your healthcare provider immediately. But if your symptoms feel severe, get emergency medical care right away.

Some Auvelity interactions may worsen depression symptoms. If you or someone you know are having thoughts of suicide or self harm, there are resources that can help. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line. 

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Written by:

Jennifer Gershman, PharmD, CPh, PACS

Jennifer Gershman, PharmD, is a licensed pharmacist in Florida. She has worked in the pharmacy industry for more than 15 years and is currently a medical writer.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed 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.

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