Bupropion and dextromethorphan

Bupropion and dextromethorphan (brand Auvelity) is an antidepressant medicine used to treat major depressive disorder (MDD) and agitation associated with dementia due to Alzheimer's disease (AD).

• When used for agitation that may happen with dementia due to Alzheimer’s disease, Auvelity should not be used as an “as-needed” treatment.

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 symptoms of depression or agitation. 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). Approval was extended on April 30, 2026, to include agitation associated with dementia due to Alzheimer's disease.

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

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 an Auvelity coupon. Ask your doctor or pharmacist if you qualify, or check the Auvelity price guide page for links.

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

• Your healthcare provider may increase your dose of bupropion and dextromethorphan during treatment. Follow the directions provided by your healthcare provider. Do not change your dose of bupropion and dextromethorphan without first talking to your healthcare provider.
• If you take bupropion and dextromethorphan 1 time a day, take your tablet in the morning.
• If your healthcare provider increases your dose to 2 times a day, take your bupropion and dextromethorphan tablets at least 8 hours apart.
• Do not take more than 2 bupropion and dextromethorphan tablets in 24 hours.
• 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, and they can do a more specific drug screening test that should not have this problem.

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.

• Depression or other mental illnesses are the most important causes of suicidal thoughts or actions.

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

• Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts, or feelings or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or the dose changes.
• Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings or if you develop suicidal thoughts or actions.
• Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms.

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:

• thoughts about suicide or dying
• new or worse depression
• feeling very agitated or restless
• trouble sleeping (insomnia)
• attempts to commit suicide
• new or worse anxiety
• panic attacks
• new or worse irritability
• acting aggressive, being angry, or violent
• an extreme increase in activity and talking (mania)
• acting on dangerous impulses
• other unusual changes in behavior or mood.

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

• have or had seizures or convulsions
• have had a head injury
• have had a heart attack or have heart problems
• have a tumor in your nervous system (brain or spine)
• have had a stroke
• have low blood sugar
• have low sodium levels in your blood
• have liver problems
• have kidney problems
• drink a lot of alcohol
• abuse prescription medicines or street drugs
• have diabetes and take oral diabetes medicines or use insulin to control your blood sugar
• have high blood pressure
• have a history of falls
• have or had bipolar disorder, or have a family history of bipolar disorder, suicide, or depression
• have high pressure in the eye (glaucoma)

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 babies. 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.

Do not take bupropion and dextromethorphan if you:

• have or had a seizure disorder
• have or had an eating disorder such as anorexia nervosa or bulimia
• have recently suddenly stopped drinking alcohol or use medicines called benzodiazepines, barbiturates, or antiseizure medicines, and you have recently suddenly stopped taking them.
• take a monoamine oxidase inhibitor (MAOI) medicine
• have stopped taking an MAOI in the last 14 days
• are being treated with the antibiotic linezolid or intravenous methylene blue
• are allergic to dextromethorphan, bupropion, or any of the other ingredients. See the end of this page for a complete list of ingredients.

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.

Common dextromethorphan and bupropion side effects

The most common dextromethorphan and bupropion side effects in people with major depressive disorder (MDD) include dizziness, diarrhea, dry mouth, excessive sweating, headache, feeling sleepy, and sexual function problems.

The most common Auvelity side effects in people with agitation that may happen with dementia due to Alzheimer's disease include:

• dizziness
• stomach upset or pain.

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:

• take higher doses of this medicine
• have certain medical problems
• take it with certain other medicines

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:

• greatly increased energy
• racing thoughts
• unusually grand ideas
• talking more or faster than usual
• severe trouble sleeping
• reckless behavior
• excessive happiness or irritability

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:

• agitation
• seeing or hearing things that are not there (hallucinations)
• confusion
• coma
• fast heartbeat
• changes in blood pressure
• dizziness
• sweating
• flushing
• high body temperature (hyperthermia)
• shaking (tremors), stiff muscles, or muscle twitching
• loss of coordination
• seizures
• nausea, vomiting, diarrhea.

Low levels of salt (sodium) in your blood (hyponatremia). Bupropion and dextromethorphan can cause low sodium levels in the blood. Symptoms include headache, trouble concentrating, memory changes, confusion, weakness, and unsteadiness. Severe or sudden cases may cause hallucinations, fainting, seizures, or coma. Untreated severe low sodium can be fatal. Older adults and people who take diuretics or become dehydrated are at higher risk. Tell your healthcare provider if you notice any of these symptoms.

Allergic reactions. This medicine may cause allergic reactions that can happen right away or later during treatment. Tell your healthcare provider right away if you develop a skin rash, swelling, itching, shortness of breath, hives, muscle or joint pain, chest pain, or fever.

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.

Usual Adult Dose for Bupropion and Dextromethorphan (Auvelity) for MDD

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.

Usual Adult Dose for Bupropion and Dextromethorphan (Auvelity) for Agitation Associated With Dementia Due to Alzheimer's Disease

Dose: One tablet (dextromethorphan/bupropion 30 mg/105 mg) once daily in the morning for 7 days, then increase to 1 tablet (dextromethorphan/bupropion 30 mg/105 mg) twice daily, separated by at least 8 hours.

On Day 15, increase the dose to the maximum dose of dextromethorphan/bupropion 45 mg/105 mg twice daily, separated by at least 8 hours, based on tolerability.

Dose modifications:

• Maximum dose in moderate renal impairment: One tablet dextromethorphan/bupropion 45 mg/105 mg by mouth once daily in the morning.
• Maximum dose in CYP2D6 poor metabolizers: One tablet dextromethorphan/bupropion 45 mg/105 mg by mouth once daily in the morning.

Comment:

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

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.

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:

• nausea
• vomiting
• drowsiness
• unresponsiveness
• changes in vision
• seizures
• hallucinating (seeing things or hearing voices that do not exist)
• coma (loss of consciousness for a period of time)
• rapid or pounding heartbeat
• loss of coordination

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:

• other medicines containing bupropion or dextromethorphan
• medicines used to treat mood, anxiety, psychotic or thought disorders, including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and MAOIs
• tricyclic antidepressants (TCAs)
• medicines used to treat migraine headaches called triptans
• theophylline
• corticosteroids
• oral diabetes medicines or use insulin to control your blood sugar
• medicines to control appetite (anorectic)
• nicotine medicines to help you stop smoking
• street (illicit) drugs
• benzodiazepines, sedatives-hypnotics (sleep medicines), or opiates
• CNS stimulants
• digoxin
• levodopa
• amantadine.

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.

• Limit or avoid using alcohol during treatment. If you usually drink a lot of alcohol, talk with your healthcare provider before suddenly stopping. If you suddenly stop drinking alcohol, you may increase your chance of having seizures.
• Do not drive a car or use heavy machinery until you know how this medicine affects you. Auvelity can affect your ability to do these things safely.

• Store at room temperature between 68°F to 77°F (20°C to 25°C).
• Store in original container.
• Keep this and all medicines out of the reach of children.

Auvelity Active ingredients: dextromethorphan hydrobromide, bupropion hydrochloride.Auvelity Inactive ingredients: carbomer homopolymer, colloidal silicon dioxide, crospovidone, glyceryl monocaprylocaprate, l-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, sodium lauryl sulfate, stearic acid, talc, and titanium dioxide. Beige tablets also contain red iron oxide and yellow iron oxide.

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