Auvelity (Dextromethorphan-Bupropion): Drug Uses, Warnings, & Dosages

What Is Auvelity & How Is it Used?

Auvelity (bupropion and dextromethorphan), is an FDA-approved medication used to treat depression, such as major depressive disorder (MDD) in adults. While it is the first medication to be approved that targets NMDA receptors, it is a combination of bupropion and dextromethorphan, two well-known drugs that have been used for years.(FN1)

Dextromethorphan works on NMDA receptors and glutamatergic neurotransmission, which is thought to play a role in the cause of MDD.(FN2) It isn’t known exactly how Bupropion works, but it is an antidepressant that has an effect on many receptors in the brain, including dopamine and norepinephrine.(FN3) Bupropion is used as an ingredient in Auvelity because it slows the metabolism, or break down, of dextromethorphan (the other ingredient in Auvelity).

Most people metabolize dextromethorphan in 3 hours, but when taken with bupropion, the metabolism is slowed down.. This allows the effects of dextromethorphan to last longer and reduces the potential side effects of taking a higher dose. Auvelity can be used to treat depression and will likely be used in patients that have not found success with other SSRI or SNRI medications.

Auvelity is approved to treat the following mental health disorder:

• Major depressive disorder 

Potential off-label uses that will require further research may include:

• Depression in children 
• PTSD 
• Anxiety disorders
• Alzheimer related depression
• Seasonal affective disorder 

Auvelity is a unique treatment for depression as it is not considered an SNRI or SSRI, but it still carries some of the same risks. It is a medication that must be taken cautiously and not combined with specific drugs. As with most antidepressants, those prescribed must understand a severe warning for suicidal risk in young patients. The approval of Auvelity may open the door for other similar medication treatments for depression that may help to improve treatment for patients.

History of Auvelity

Axsome, the manufacturer of Auvelity, is the first company to have an approved antidepressant that targets NMDA receptors. Early in the research and study of Auvelity, the FDA designated it as a breakthrough therapy. Given the promising treatment results and the need for improved antidepressant treatment, it is likely that other pharmaceutical companies will follow suit and develop similar medications in the future. While Auvelity has been approved as of August 2022, Axsome will still be responsible for further studies to ensure safe and effective use.

What Are Common Auvelity Dosages & Delivery Methods?

Auvelity is only available as an extended-release tablet that contains the following:

• 45 mg of dextromethorphan
• 105 mg of bupropion

Studies have shown that this combination is the proper ratio to improve symptoms of depression. It is important to note that the tablet should be swallowed whole and not crushed, chewed, or split because it is an extended-release medication. Auvelity can be taken with or without food.

The starting dosage is one tablet per morning for three days to allow the body to adjust, then a standard dosage of one tablet twice daily with 8 hours in between. If you have impaired renal function or are a poor CYP2D6 enzyme metabolizer, your doctor may also choose to keep your dosage at one tablet every morning.

Warnings & Associated Risks of Auvelity

Understanding the risks associated with Auvelity use is essential before starting treatment. For patients with lower kidney function and irregular liver metabolism, Auvelity can still be used but may require smaller doses to be safe. With the same hope to prevent liver damage, patients should avoid the consumption of alcohol during treatment with Auvelity.

Other examples of individuals with a higher risk of side effects with Auvelity are included below. Anyone considering Auvelity should talk with their doctor about their health history to determine if it is safe for them:

• Young adults age 24 and younger have an increased risk of developing suicidal ideation
• When Bupropion is taken in high doses, those with a history of seizures can have a higher chance of experiencing them again.
• Patients diagnosed with anorexia or bulimia also have an increased risk of seizures.
• Patients with uncontrolled high blood pressure may not be able to take Auvelity as it can cause high blood pressure. This risk is elevated when Auveility is combined with other medications affecting serotonin.
• Patients with bipolar disorder are at a higher risk for developing mania and should be screened and monitored for signs of a developing manic episode while taking Auvelity.
• Both active ingredients in Auvelity are known to cause psychosis at high doses. Therefore patients should not take Auvelity with other medications containing bupropion or dextromethorphan.
• Taking Auvelity can put some patients at risk of developing Glaucoma. Patients should complete eye health screening before starting Auvelity, and prescribers should not use it in patients with untreated anatomically narrow angles.
• Taking Auvelity with other medications like SSRIs or tricyclic antidepressants increase the risk for serotonin syndrome, which can be fatal in some cases.
• Auvelity is known to cause fetal toxicity when taken by pregnant patients and should not be used in pregnancy.
• Patients should avoid alcohol, benzodiazepines, barbiturates, or antiepileptic drugs while taking Auvelity as they can increase the risk for serious side effects.

Auvelity is unsafe to take during pregnancy and should not be used. Parts of Auvelity can be excreted in milk during breastfeeding. Therefore, Auvelity should not be used during breastfeeding, and at least five days should separate the last dose and the start of breastfeeding.

There are many risks with Auvelity, and speaking with your doctor is the first step to navigating them. It is essential to discuss, before starting Auvelity, your complete health history with your doctor to determine if Auvelity can be a helpful and safe medication for you.¹

Side Effects of Auvelity 

Patients using Auvelity can experience side effects, and it is crucial to understand what they are so you know how to respond if you experience any. Some Auvelity side effects can be severe and require immediate help, while others may go away with time or dosage changes. It is essential to follow the directions for taking Auvelity to avoid additional overdose side effects.

Possible severe side effects of Auvelity may include:⁴

• Suicidal ideation: It is important to immediately let someone know if you have thoughts of self-harm or a sudden change in mood.
• Seizures: These are rare but severe side effects and require immediate attention to prevent injury and death.
• Manic episodes: Patients may require medical attention immediately if the episode is severe. It is crucial to alert your doctor immediately so Auvelity can be safely stopped.
• Increased blood pressure: If left untreated, it can become a dangerous side effect leading to additional health conditions.
• Unusual behavior changes: This can include increased anxiety, panic attacks, or paranoia. If you experience sudden mood changes, alert your healthcare team right away.
• Eye/vision problems: Specifically narrow-angle glaucoma.

Another possible severe side effect is Serotonin Syndrome. It can happen by taking a medication that affects serotonin in the body and taking multiple drugs that affect serotonin increases the risk further. Auvelity should not be combined with other antidepressants, migraine medications, or certain pain medications. It is best always to alert your doctor and pharmacist of any medications you are taking.

Serotonin syndrome symptoms can include:

• Agitation
• Confusion
• Rapid heartbeat
• Sweating
• Shivering
• Loss of coordination

Common mild side effects can include:¹

• Dizziness
• Nausea
• Headache
• Diarrhea
• Drowsiness
• Dry mouth
• Sexual dysfunction
• Excessive sweating
• Anxiety
• Constipation
• Decreased appetite
• Insomnia
• Joint pain
• Fatigue
• Pins and needles sensation (Paraesthesia)
• Blurred vision

Your doctor will start with a lower dose for a few days before increasing to  the recommended dosage.¹ This helps to reduce unwanted side effects associated with starting Auvelity too quickly. Communicating any experienced side effects with your care team to ensure safe and effective treatment is important so prescribers can make appropriate changes.

Allergic Reactions to Bupropion/Dextromethorphan in Auvelity 

Patients allergic to any part of Auvelity should not take Auvelity. It is important to remember that while Auvelity is new, it contains bupropion and dextromethorphan that patients may have taken before. If you are allergic to certain cough medications, Wellbutrin, or Zyban (a smoking cessation medication), you should not take Auvelity.¹

Medication Interactions with Auvelity

Disclaimer: Taking medications, herbs, or supplements alongside Auvelity can change how it works in your body or increase the risk for serious side effects. This article does not consider all possible interactions. Let your doctor, psychiatrists, and pharmacists know about all products you use, such as prescription medication, nonprescription drugs, and herbal supplements. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Auvelity is specifically made to provide the maximum benefit of the drugs it contains. Many medications can cause Auvelity not to work or cause unwanted and sometimes dangerous side effects. Auvelity can also cause some medicines not to work correctly or cause dangerously high levels of the other drugs in your body.

Some substances that negatively interact with Auvelity include:¹

• Other medications that contain dextromethorphan or bupropion can cause unsafe levels of both drugs in the body.
• MAOIs should never be taken with Auvelity or within two weeks as it increases the risk of hypertensive crisis and serotonin syndrome.
• Other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids can all increase the risk of experiencing a seizure.
• SSRIs or tricyclic antidepressants, when taken with Auvelity, may cause serotonin syndrome.
• Strong CYP2D6 inhibitors can cause dextromethorphan to last longer in your body, potentially causing damaging effects on the central nervous system.
• Strong  CYP2B6 Inducers can cause Auvelity not to work as well as it should.
• Digoxin (blood pressure medicine) and Auvelity interact and can decrease the effects of digoxin.
• Auvelity taken with alcohol can increase the risk of central nervous side effects, as well as lower a person’s alcohol tolerance.

What to Do If You Overdose

Overdose of any medication can be life-threatening and should be taken seriously. Call 911 or the poison center (1-800-222-1222) if an overdose of Auvelity is suspected. Symptoms of Auvelity will include any overdose symptom of dextromethorphan or bupropion.

Symptoms of an overdose from auvelity can include:¹

• Nausea
• Vomiting
• Respiratory
• Depression
• Seizures
• Tachycardia
• blurred vision
• Hallucinations
• Loss of consciousness
• Mental status changes
• Irregular heartbeats.

Since Auvelity is an extended-release medication containing bupropion, it is vital to remember that an overdose reaction, like seizures, can be delayed for up to 24 hours.⁵ If you suspect you may have overdosed, you should call 9-1-1 and seek emergency medical care as soon as possible.

What if I Miss a Dose of Auvelity?

If you miss a dose, taking it as soon as you remember is crucial. If the time is more than halfway until the next dose, skip the missed dose and continue taking Auvelity as prescribed on the next scheduled dose. Do not double up on your dose, as it is dangerous and can lead to serious side effects. When patients feel their depression is gone, it may lead them to miss a dose intentionally or unintentionally, as some feel it is unnecessary. Auvelity is a medication intended to be taken daily even if the patient does not feel depressed.

Questions to Ask Your Health Team About Auvelity (Bupropion/Dextromethorphan)

Auvelity can be an effective treatment option for depression, and your doctor or psychiatrist is the place to start. Sharing your complete health history and medication regimen with your doctor is crucial to reducing your risk of harmful side effects or complications. It is also important to take the time to ask questions about treatment with Auvelity. Knowing what your experience on Auvelity will look like can make the process much easier and less stressful.

Questions to ask your care team about before taking Bupropion/Dextromethorphan include:

• What should I do if I am having thoughts of suicide or self-harm?
• Is it safe to take Auvelity with my other medications?
• Will my mental health insurance cover Auvelity?
• How will I know that Auvelity is working, and how long will it take?
• Will Auvelity work as fast as other antidepressants?
• Does my medical history increase my risk of side effects?
• How long can I expect side effects to last?
• What side effects should I seek immediate medical attention for?
• How often should we check in while I am taking Auvelity?
• Should I let my therapist know I am taking this medication?
• How can I tell this drug is effective if it just came to the market?
• What if I want to become pregnant while taking Auvelity?
• Which of my medications can I replace with Auvelity?
• What should I do if I want to stop taking Auvelity?
• How long will I need to take Auvelity?

Final Thoughts

Auvelity is a newly approved medication for depression in adults. It is a combination of two previously known drugs, dextromethorphan, and bupropion. Auvelity is being used to target a newly understood potential cause of depression, NMDA receptors. Some risks of taking Auvelity include seizures, high blood pressure, and thoughts of suicide in young adults. It is also essential to know that Auvelity can dangerously interact with many medications. Talk to your doctor or mental health care team to determine if Auvelity could be a good fit for you!

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