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Bupropion and dextromethorphan

Brand name: Auvelity
Dosage form: extended release tablets (45 mg/105 mg dextromethorphan hydrobromide/ bupropion hydrochloride)
Drug class: Miscellaneous antidepressants

Medically reviewed by Melisa Puckey, BPharm. Last updated on Oct 3, 2024.

What is bupropion and dextromethorphan?

Bupropion and dextromethorphan (brand Auvelity) is an antidepressant medicine used to treat major depressive disorder (MDD), which is a specific type of depression. Dextromethorphan and bupropion is a rapid-acting antidepressant that started working as early as 1 week, and patients' depression symptoms continued to improve over time when compared to placebo in a 6-week clinical study for MDD (Study 1, NCT04019704).

Dextromethorphan and bupropion is thought to work by increasing the amount of glutamate (a chemical messenger) available in your brain, which may positively affect your mood and ease depressive symptoms. It may also weakly affect your brain's other neurotransmitters, norepinephrine and dopamine.

Dextromethorphan and bupropion (Auvelity) became an FDA-approved medicine on August 18, 2022, for adults with major depressive disorder (MDD).

How does dextromethorphan and bupropion work?

Dextromethorphan and bupropion work together for their antidepressant effect. The active ingredient dextromethorphan belongs to a drug class called N-methyl D-aspartate (NMDA) receptor antagonists (which means it blocks these receptors) and is also an agonist at the sigma-1 receptors (stimulates these receptors), these effects help improve depressive symptoms. 

The other active ingredient, bupropion, belongs to a class of medicines called NDRIs (norepinephrine and dopamine reuptake inhibitors) and may have an antidepressant effect that is thought to be due to its effect on neurotransmitters (chemical messengers) like norepinephrine and dopamine in your brain. Bupropion is also a CYP2D6 inhibitor that stops dextromethorphan from breaking down so that dextromethorphan levels are higher and last longer. 

Dextromethorphan mechanism of action is an uncompetitive N-methyl D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist. Bupropion mechanism of action is as an aminoketone and CYP450 2D6 inhibitor.

What is the cost of dextromethorphan and bupropion?

The cost of bupropion and dextromethorphan drugs varies depending on your insurance plan and which pharmacy you use. Refer to our Auvelity price guide page for more information about the cost of Auvelity.

You may also be eligible for an Auvelity savings card or Auvelity coupon. Ask your doctor or pharmacist if you qualify, or check the Auvelity price guide page for links.

Bupropion and dextromethorphan side effects

Common dextromethorphan and bupropion side effects

The most common dextromethorphan and bupropion side effects include dizziness, diarrhea, dry mouth, excessive sweating, headache, feeling sleepy, and sexual function problems.

Serious bupropion and dextromethorphan side effects

Dextromethorphan and bupropion may cause serious side effects, including seizures, increase in blood pressure, manic episodes, unusual thoughts or behaviors, eye problems (angle-closure glaucoma), dizziness

Seizures. There is a risk of seizures during treatment with this medicine. The risk is higher in people who:

Do not take Auvelity with other medicines unless your healthcare provider tells you to.
If you have a seizure during treatment, stop taking this medicine and call your healthcare provider right away. Do not take this medicine again if you have a seizure, or serotonin syndrome.

Increases in blood pressure (hypertension). Some people may get high blood pressure during treatment. Your healthcare provider should check your blood pressure before you start taking and during treatment.

Manic episodes. Manic episodes may happen in people with bipolar disorder who take Auvelity. Symptoms may include:

Unusual thoughts or behaviors. One of the ingredients in Auvelity (bupropion), can cause unusual thoughts or behaviors, including delusions (believing you are someone else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that people are against you), or feeling confused. If this happens to you, call your healthcare provider.

Eye problems (angle-closure glaucoma). Auvelity may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your healthcare provider if you have eye pain, changes in your vision, or swelling or redness in or around the eye.

Dizziness. this medicine may cause dizziness, increasing your fall risk.

Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take Auvelity with certain other medicines. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of serotonin syndrome:

These are not all the possible side effects. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Also, see the Warnings section.

Bupropion / dextromethorphan side effects (more detail)

Warnings

Bupropion and dextromethorphan may cause other serious side effects, including an increased risk of suicidal thoughts and actions.
Bupropion with dextromethorphan and other antidepressant medicines may increase suicidal thoughts and actions in some children, adolescents, and young adults, especially within the first few months of treatment or when the dose is changed. This medicine is not for use in children.

How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

Call your healthcare provider or get emergency help right away if you have any of the following symptoms, especially if they are new, worse, or worry you :

Before taking dextromethorphan and bupropion

Before you start treatment, tell your healthcare provider about all your medical conditions, including if you:

Pregnancy

Tell your healthcare provider if you are pregnant or plan to become pregnant. Bupropion with dextromethorphan may harm your unborn baby if you take it during pregnancy. Dextromethorphan and bupropion (Auvelity) is not recommended during pregnancy.
If you become pregnant or think you are pregnant during treatment, tell your healthcare provider right away. Your healthcare provider will prescribe another treatment for females who plan to become pregnant.
There is a pregnancy registry for females who are exposed to this medicine during pregnancy. The purpose of the registry is to collect information about the health of females exposed to Auvelity and their baby. If you become pregnant during treatment, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visit online at https://womensmentalhealth.org/clinical-and-research programs/pregnancyregistry/antidepressants/.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. One of the active ingredients called bupropion, passes into your breast milk. Do not breastfeed during treatment with this medicine and for 5 days after the final dose.

Bupropion / dextromethorphan pregnancy and breastfeeding warnings (more detail)

Who should not take dextromethorphan and bupropion?

Do not take bupropion and dextromethorphan if you:

Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including the antibiotic linezolid or intravenous methylene blue.

Do not start this medicine if you stopped taking an MAOI in the last 14 days.

Do not start taking an MAOI for at least 14 days after you stop treatment with Auvelity.

How should I take bupropion and dextromethorphan?

Take dextromethorphan and bupropion exactly as your healthcare provider tells you to take it.

The usual adult dose is one Auvelity (bupropion and dextromethorphan) tablet 1 time a day for 3 days, then increase your dose to 2 times a day (taken at least 8 hours apart).

Swallow tablets whole. Do not crush, chew, or divide the tablets.

Tablets may be taken with or without food.

Do not take more than 2 tablets in 24 hours.

Your blood pressure will need to be checked often.

Do not stop using this medicine suddenly. Ask your doctor before stopping the medicine.

This medicine may cause false results on a drug-screening urine test. Tell the laboratory staff that you take this medicine, they can do a more specific drug screening test that should not have this problem.

Dosing information

Usual Adult Dose for bupropion and dextromethorphan (Auvelity)

Dose: One tablet once daily in the morning for three days, then increase to the maximum recommended dosage of one tablet twice daily, separated by at least 8 hours.

Dose modifications: Moderate renal impairment: One tablet by mouth once daily in the morning. CYP2D6 poor metabolizers: One tablet by mouth once daily in the morning.

Comment: Prior to initiating treatment with this medicine assess blood pressure; screen patients for history of bipolar disorder, mania, or hypomania; and determine if patients are receiving any other medications that contain bupropion or dextromethorphan.

Dosage form and strength: Extended-release tablet containing dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg.

Detailed Bupropion / dextromethorphan dosage information

Trintellix, Vraylar, sertraline, trazodone, Lexapro, Zoloft, Cymbalta, Prozac

What happens if I miss a dose?

If you miss a dose, do not take an extra dose to make up for the dose you missed. Wait and take your next dose at the regular time. Do not take more than 1 dose of this medicine at a time.

What happens if I overdose?

In case of overdose, call the poison control helpline at 1-800-222-1222. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

What other drugs will affect bupropion and dextromethorphan?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Dextromethorphan and bupropion (Auvelity) and some other medicines may affect each other causing possible serious side effects. Auvelity may affect the way other medicines work and other medicines may affect the way Auvelity works.

Especially tell your healthcare provider if you take:

Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take Auvelity with your other medicines.

Do not start or stop any other medicines during treatment without talking to your healthcare provider first. Stopping treatment suddenly may cause you to have serious side effects.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

Bupropion / dextromethorphan drug interactions (more detail)

What should I avoid while taking this medicine?

Storage

Auvelity Ingredients

Auvelity Active ingredients: dextromethorphan hydrobromide, bupropion hydrochloride.
Auvelity Inactive ingredients: l-cysteine hydrochloride monohydrate, carbomer homopolymer, microcrystalline cellulose, colloidal silicon dioxide, crospovidone, stearic acid, and magnesium stearate.

Auvelity Company

​​Auvelity Distributed and Marketed by: Axsome Therapeutics, Inc. New York, NY 10007

Popular FAQ

Does Auvelity work better than Wellbutrin?

Auvelity worked significantly better than Wellbutrin (bupropion) at relieving symptoms of depression in a small randomized double-blind, parallel trial that lasted for 6 weeks. It also had a faster onset of effect, with improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) score being observed as early as week 1 and differences being statistically significant by week 2. Continue reading

Auvelity vs. Wellbutrin: Effectiveness for Depression?

Both Auvelity and Wellbutrin are effective for depression but a small RCT (n=80) reported that Auvelity worked significantly better than Wellbutrin and took less time to start working. 43 people prescribed Auvelity experienced an overall decrease in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 13.7 points after 6 weeks compared to a decrease of 8.8 points in the 37 people prescribed bupropion (least-squares mean difference=-4.9; 95% CI=-3.1, -6.8). Continue reading

How does Auvelity work / moa?

Auvelity works in several different ways because it contains two different ingredients, dextromethorphan and bupropion, although the exact way it works for depression is unknown. The dextromethorphan component targets the NMDA receptor (N-methyl-D-aspartate), the serotonin transporter (SERT), the norepinephrine transporter (NET), and the sigma-1 receptor, to regulate levels of glutamate and other neurotransmitters such as serotonin and norepinephrine. Continue reading

What makes Auvelity different from other antidepressants?

Auvelity is a combination oral tablet for depression containing dextromethorphan and bupropion that works differently from other antidepressants because it has a direct effect on the N-methyl-D-aspartate (NMDA) receptor as well as possibly other traditional neurotransmitter effects. It also works much faster than traditional antidepressants, and it does appear to be more effective. Continue reading

Does Auvelity cause weight gain or loss?

Weight gain has not been reported with Auvelity, but in one 6-week study, participants lost, on average, half a pound, while those taking placebo gained about one pound. Animal studies have also reported that the administration of dextromethorphan/bupropion did not affect body weight, weight gain, or food consumption. Continue reading

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References

  1. Auvelity Package Insert - FDA

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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