Auvelity for depression and agitation in Alzheimer's disease

Auvelity is an oral extended-release tablet combining dextromethorphan hydrobromide and bupropion hydrochloride. It is approved for treating major depressive disorder (MDD) in adults and agitation associated with dementia due to Alzheimer’s disease.

Major depressive disorder (MDD) in adults: Auvelity is prescribed for the treatment of MDD.

Agitation associated with dementia due to Alzheimer’s disease: Auvelity is indicated to manage agitation in patients with this condition but is not approved for as-needed use.

dextromethorphan hydrobromide, bupropion hydrochloride

Auvelity combines two active ingredients: dextromethorphan acts as an uncompetitive antagonist of NMDA receptors and a sigma-1 receptor agonist, modulating glutamate signaling in the brain, while bupropion functions as an aminoketone antidepressant and CYP450 2D6 inhibitor, which increases dextromethorphan levels by slowing its metabolism.

General

• Swallow tablets whole; do not crush, divide, or chew.
• Administer orally with or without food.

For major depressive disorder in adults

• Start with 45 mg dextromethorphan/105 mg bupropion once daily in the morning for 3 days.
• From day 4, increase to 45 mg/105 mg twice daily (at least 8 hours apart). Do not exceed two doses per day.

For agitation associated with dementia due to Alzheimer’s disease

• Start with 30 mg dextromethorphan/105 mg bupropion once daily in the morning.
• On day 8, increase to 30 mg/105 mg twice daily (≥8 hours apart), based on tolerability.
• On day 15, increase to the maximum 45 mg/105 mg twice daily as tolerated, not exceeding two doses per day.

Dose adjustments

• Moderate renal impairment (eGFR 30–59 mL/min/1.73 m²): maximum recommended dose is one 45 mg/105 mg tablet once daily in the morning for both indications.
• CYP2D6 poor metabolizers or patients taking strong CYP2D6 inhibitors: recommended maximum dose is one tablet 45 mg/105 mg once daily for MDD; for agitation, start with one 30 mg/105 mg tablet once daily and increase to one 45 mg/105 mg tablet once daily as tolerated.
• Allow at least 14 days after discontinuing monoamine oxidase inhibitors (MAOIs) before starting Auvelity, and vice versa.

• Seizure disorder
• Current or prior diagnosis of bulimia or anorexia nervosa
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Use with MAOIs or within 14 days of stopping MAOIs; starting Auvelity with reversible MAOIs (linezolid, IV methylene blue) is contraindicated
• Known hypersensitivity to bupropion, dextromethorphan, or any component of Auvelity

Suicidal thoughts and behaviors

Antidepressants, including Auvelity, increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients; therefore, close monitoring is essential especially during initial treatment and dose changes. Auvelity is not approved for pediatric use.

Seizure risk

Risk is dose-related and increased in patients with seizure disorders, eating disorders (bulimia, anorexia nervosa), abrupt discontinuation of alcohol or certain drugs, or concomitant medications lowering seizure threshold. Auvelity is contraindicated in such patients. Discontinue if seizure occurs.

Blood pressure and hypertension

Auvelity can cause increased blood pressure and hypertension; assess blood pressure before starting and monitor periodically during treatment.

Activation of mania/hypomania

Screen patients for bipolar disorder before starting Auvelity; treatment may induce manic episodes.

Psychosis and neuropsychiatric reactions

Bupropion and dextromethorphan in Auvelity may cause psychosis, hallucinations, paranoia, or confusion; monitor patients and instruct to report such symptoms promptly.

Angle-closure glaucoma

May trigger glaucoma attacks in patients with untreated anatomically narrow angles.

Dizziness and fall risk

Auvelity may cause dizziness; caution is advised to reduce fall risk, especially in patients with motor impairment.

Serotonin syndrome

Increased risk when combined with SSRIs or tricyclic antidepressants; discontinue Auvelity if it occurs.

Embryo-fetal toxicity

Auvelity may cause fetal harm; advise pregnant patients of risks and discontinue use in pregnancy.

Hyponatremia

Can occur, sometimes associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Common side effects

• Dizziness (occurring in 14% of depression patients; 9% in dementia-associated agitation)

Serious side effects

• Seizures
• Hypertension
• Psychosis and neuropsychiatric symptoms
• Serotonin syndrome
• Anaphylaxis and hypersensitivity reactions (including Stevens-Johnson syndrome)
• Angle-closure glaucoma
• Hyponatremia

• Concurrent use with monoamine oxidase inhibitors (MAOIs) is contraindicated due to risk of hypertensive crisis and serotonin syndrome; allow at least 14 days washout between therapies.
• Use with strong CYP2D6 inhibitors requires dose adjustment to once daily dosing.
• Concurrent use with other bupropion- or dextromethorphan-containing products increases risk of seizure and neuropsychiatric effects; avoid if possible.
• Co-administration with SSRIs or tricyclic antidepressants increases serotonin syndrome risk.

Pregnancy

Auvelity may cause harm to the fetus. Pregnant women should be advised of the potential risks and consider alternative treatments. Discontinue Auvelity if pregnancy occurs.

Lactation

Information on lactation is not provided in the supplied source.

Dextromethorphan overdose can cause toxic psychosis, stupor, coma, and hyperexcitability. Bupropion overdose may increase seizure risk. Management includes immediate medical attention and supportive care.