Auvelity (dextromethorphan HBr/bupropion HCl) for Alzheimer’s disease

What is Auvelity for Alzheimer’s disease?

Auvelity (dextromethorphan hydrobromide/bupropion hydrochloride) is an oral therapy used to manage agitation related to dementia in people with Alzheimer’s disease.

Alzheimer’s is a neurodegenerative disease that commonly leads to dementia, a decline in cognitive abilities severe enough to interfere with daily life. People with dementia can become easily agitated due to physical discomfort, confusion, frustration, and other factors.

Auvelity contains two active ingredients: dextromethorphan and bupropion. Dextromethorphan helps regulate brain chemicals involved in mood and behavior, while bupropion prolongs dextromethorphan’s effects in the body. It is not known exactly how Auvelity works, but it is generally thought to normalize brain signaling imbalances that contribute to agitation.

The medication, sold by Axsome Therapeutics, is also used to treat adults with major depressive disorder.

Therapy snapshot

Who with Alzheimer’s disease can take Auvelity?

In the U.S., Auvelity is approved for the treatment of agitation in people with dementia due to Alzheimer’s disease. The treatment is contraindicated, or should not be used, by people who:

• have a seizure disorder
• have a current or prior diagnosis of bulimia or anorexia nervosa
• are undergoing abrupt discontinuation of certain substances, including alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
• used monoamine oxidase inhibitors, a class of antidepressants, in the last two weeks
• have a known history of immune reactions (hypersensitivity) to any active or inactive ingredient in the medication

It is also recommended that Auvelity be avoided by anyone who is breastfeeding or who has severe liver or kidney impairment.

How is Auvelity administered in Alzheimer’s disease?

Auvelity is taken as an oral tablet, with or without food. The tablets should be swallowed whole and never crushed, divided, or chewed.

The recommended starting dose is 30 mg dextromethorphan/105 mg bupropion once daily in the morning. The dose may be gradually increased to the maximum recommended maintenance dose of 45 mg/105 mg, taken twice daily, with the doses being given at least eight hours apart.

People with moderate kidney impairment, those with naturally low CYP2D6 enzyme activity, or individuals using certain medications may need dose adjustments.

Auvelity is not indicated as an “as-needed” treatment for Alzheimer’s-related agitation. It should be taken every day, and no more than two doses should be taken in a day.

Auvelity in Alzheimer’s disease clinical trials

Auvelity’s approval for Alzheimer’s was supported by two clinical trials involving people with probable Alzheimer’s disease, dementia, and agitation who were between the ages of 65 and 90.

• In the Phase 2/3 ADVANCE-1 trial (NCT03226522), participants on Auvelity were found to have significant improvements in a clinician-rated measure of agitation relative to a placebo after five weeks. More people in the Auvelity group than in the placebo group were rated by their clinician as at least minimally improved on a measure of overall clinical function.
• In the Phase 3 ACCORD-2 trial (NCT04947553), people who showed a clinical response to Auvelity either continued treatment or switched to a placebo. The results showed that people who stayed on Auvelity took significantly longer to experience a recurrence of agitation symptoms than people who switched over to the placebo.

Auvelity side effects

The most common side effects of Auvelity in people with Alzheimer’s disease include:

• dizziness
• indigestion

Auvelity comes with a boxed warning that the medication increases the risk of suicidal thoughts and behaviors in children and young adults using antidepressants, for which careful monitoring is required. Auvelity also comes with warnings for other potentially serious adverse events, including:

• seizures
• high blood pressure
• psychiatric reactions, including delusions or hallucinations
• low blood sodium levels
• angle-closure glaucoma, an eye complication
• dizziness that increases the risk of falls or other safety issues
• serotonin syndrome, a life-threatening neurological complication, when used with certain other medications
• mania or hypomania, types of mood alterations, especially in people with bipolar disorder or risk factors for bipolar disorder

Individuals will be evaluated for risk factors of these complications before treatment starts and monitored for their occurrence regularly. Treatment may need to be stopped if certain complications occur.

Patients should tell their doctors about all other medications and substances they are using, as there could be unsafe interactions with Auvelity.

Auvelity could also cause harm to a developing fetus. It should be discontinued if pregnancy occurs and avoided in patients who plan to become pregnant.