This article was first published on August 30, 2022.
The combination of dextromethorphan and bupropion (brand name Auvelity™) was approved by the FDA in 2022 for the treatment of major depressive disorder. This combination product is the first oral N-methyl D-aspartate (NMDA) receptor antagonist approved for the treatment of major depressive disorder (MDD) in adults.
This combination product was developed by Axesome Therapeutics and is expected to be available in US markets in the fourth quarter of 2022.
Note: Esketamine nasal spray (Spravato®) is also an N-methyl D-aspartate (NMDA) receptor antagonist that has FDA indications for treatment-resistant depression (TRD) in adults and depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.
On this page, we will provide basic information about this medication. Links to other articles on this website with more advanced information and tips related to this medication and related topics are provided below—under Related Pages below.
Treatment of major depressive disorder (MDD) in adults.
Note that the FDA indication is NOT for “treatment-resistant” major depressive disorder or major depressive disorder that has not responded adequately to a previous trial of an antidepressant.
Mechanism of action/ Pharmacodynamics
– Dextromethorphan is an NMDA receptor antagonist and sigma-1 receptor agonist.
– Bupropion prolongs the action of dextromethorphan by inhibiting CYP450 2D6, which metabolizes dextromethorphan. This leads to MUCH higher and sustained levels of dextromethorphan, which are needed for the central nervous system effects.
The commonest side effects of dextromethorphan-bupropion (occurring in 5% or more of patients and at least twice the rate of placebo) were: dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.
Less common side effects (occurring in 2% or more of patients and at least twice the rate of placebo) were: anxiety, constipation, decreased appetite, insomnia, arthralgia, paresthesia, and blurred vision.
Note: Dextromethorphan-bupropion was NOT associated with psychotomimetic effects, weight gain, or sexual dysfunction (Iosifescu et al., 2022; Tabuteau et al., 2022).
Warnings and Precautions
a) May be associated with a dose-related risk of seizures. Discontinue treatment in case of seizures.
b) May increase blood pressure. Screen for hypertension before starting treatment and monitor periodically during treatment.
c) Screen for bipolar disorder as it may activate mania or hypomania
d) Dose-related neuropsychiatric reactions may occur. Review medications to confirm that the patient is not taking any other medications containing dextromethorphan and/or bupropion. The patient should be instructed to contact a healthcare provider if neuropsychiatric symptoms develop.
e) Bupropion may cause pupillary dilation which may precipitate angle closure glaucoma in some patients.
f) May cause dizziness. Patients should be informed about the risk of falls and asked to take precautions while driving or operating machinery.
g) Use of Auvelity™ with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants may increase the risk of serotonin syndrome. Discontinue treatment if that occurs.
h) Fetal toxicity: Women should be warned about the risk of harm to a fetus during pregnancy. Discontinue treatment in women who are pregnant or planning to become pregnant and suggest alternatives if needed.
The image below shows the boxed warning from the full Prescribing Information for Auvelity™.
Dosage and Administration
Before starting Auvelity:
a) check the patient’s blood pressure
b) screen for prior history of bipolar disorder, mania, or hypomania
c) review medications with patients to confirm that patient is not taking any medications containing dextromethorphan and/or bupropion.
Initial: One tablet once daily in the morning
Maximum: One tablet two times daily with a gap of at least 8 hours
Swallow the whole tablet; do not crush, divide, or chew.
a) Moderate renal impairment (30-59 ml/min/1.73 m2): Dosage adjustment is recommended. Limit to one tablet once daily in the morning.
b) Severe renal impairment (15-29 ml/min/1.73 m2): Not recommended
c) Mild to moderate hepatic impairment: No dose adjustment is necessary
d) Severe hepatic impairment: Not recommended
e) CYP2D6 poor metabolizers: Limit to one tablet once daily in the morning
Dosage forms and strengths
Extended-release tablets: Each tablet contains 45 mg of dextromethorphan and 105 mg of bupropion.
Important! This page does not provide all the information needed to prescribe this medication. Please refer to the full Prescribing Information (see link below) before prescribing this medication.
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