What Is Auvelity, and Why Does It Matter?
Auvelity (dextromethorphan and bupropion) is an extended-release tablet that combines two medicines, and you take it by mouth. The FDA has expanded its use from major depressive disorder (MDD) to include agitation linked to dementia due to Alzheimer’s disease in adults.
This matters because it is the first FDA-approved option for this type of agitation that is not an antipsychotic medicine. Agitation can be hard to manage, and many people worry about safety issues with antipsychotics in older adults.
Dextromethorphan affects brain signaling through the N-methyl D-aspartate (NMDA) receptor and the sigma-1 receptor. Bupropion is an antidepressant that blocks an enzyme called CYP2D6. That block raises dextromethorphan levels in your body. The label notes that exactly how this combination helps agitation in Alzheimer’s dementia (and major depressive disorder) is not fully understood.
The FDA describes agitation as a common and upsetting symptom. It can show up as too much movement or verbal or physical aggression. It can also greatly affect the quality of life for you and for the people who care for you. In a report from a later-stage study of this same drug combination, agitation was described as affecting as many as 70% of people with Alzheimer’s disease.
Why Was It Approved?
For agitation tied to dementia due to Alzheimer’s disease, the FDA says Auvelity worked in two randomized studies.
In one short study that lasted five weeks, Auvelity was compared with placebo. The main outcome was the change at week five on the Cohen-Mansfield Agitation Inventory (CMAI). This is a clinician-rated scale that uses caregiver reports to score agitation. The FDA reports this drug improved CMAI scores more than a placebo did.
A second study used a “withdrawal” (relapse-prevention) approach. First, people took the drug and had to reach a sustained response. Then they were randomized either to stay on Auvelity or switch to a placebo. The main outcome was how long it took for agitation to return. The FDA reports that staying on Auvelity delayed relapse compared with switching to a placebo.
Side effects were common in studies. For the Alzheimer’s-related agitation use, the FDA lists dizziness, upset stomach, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction, and uncontrolled sweating among the more common effects. In the short placebo-controlled agitation study described in the label, the most common reactions (happening in at least 25% of people and more than twice as often as placebo) were dizziness and dyspepsia (indigestion).
What Do I Need to Know?
For agitation associated with dementia due to Alzheimer’s disease, the label uses a gradual increase in dose. You start with Auvelity 30 milligrams/105 milligrams once each morning. If you are tolerating it, the dose is raised on day eight to 30 milligrams/105 milligrams twice daily. If you are still tolerating it, the dose is increased again on day 15 to the maximum recommended dose of 45 milligrams/105 milligrams twice daily.
Do not take more than two doses in one day. Swallow the tablet whole. Do not crush it, split it, or chew it.
You can take Auvelity with food or without food. The label notes that drug levels reach a steady level in the body within about eight days. You should leave at least eight hours between doses, and you should not take more than two tablets in a day.
Before you begin Auvelity, the FDA and label advise your health care provider to check your blood pressure, ask about bipolar disorder in you or your family, and review your medicines to make sure you are not already taking another product that contains bupropion or dextromethorphan.
Auvelity carries a boxed warning about suicidal thoughts and behaviors in adolescents and young adults who take antidepressants. Close monitoring is recommended, especially early in treatment. The medicine can also cause seizures, and seizure risk increases as the dose goes up. It is contraindicated if you have a seizure disorder. Your blood pressure can also rise, so monitoring is advised. The FDA also notes a risk of mania or hypomania in people who may be prone to these mood changes.
The label states Auvelity is not approved to be used “as needed” for agitation. Do not use it with a monoamine oxidase inhibitor (MAOI), and do not start it within 14 days of stopping an MAOI, because serious interactions can occur. The label also warns about the risk of serotonin syndrome, especially if you take certain antidepressants such as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs).