FDA approves Auvelity for agitation linked to Alzheimer’s dementia

The FDA has approved Auvelity to treat agitation associated with dementia due to Alzheimer’s disease in adults. Agitation can include unusually high activity, or verbal or physical aggression. It can be distressing for the person with Alzheimer’s disease as well as family members and caregivers.

Auvelity is an extended-release tablet containing two medicines: dextromethorphan hydrobromide and bupropion hydrochloride. Extended release means the medication is designed to release over time. The FDA first approved Auvelity in 2022 for major depressive disorder in adults. This new decision expands its approved use.

According to the FDA, Auvelity is the first FDA-approved treatment for this type of agitation that is not an antipsychotic. That description matters because it identifies a new approved treatment category, but it does not mean the medicine is right for every person with Alzheimer’s-related agitation.

The approval was supported by two randomized studies. In randomized trials, participants are assigned by chance to different treatment groups. This approach can help researchers make a fairer comparison between a medicine and a placebo, an inactive treatment.

The first trial lasted five weeks. Participants received either Auvelity or placebo. Researchers measured change in agitation using the Cohen-Mansfield Agitation Inventory, or CMAI. This is a caregiver-reported survey that tracks how often agitated behaviors occur in older people. The FDA said Auvelity was significantly better than placebo at improving CMAI scores by week five.

The supplied information does not say how many people took part in that trial. It also does not provide the average score changes, the size of the difference between groups, or other numerical details that would show how large the benefit was for participants.

The second study used a different design called a randomized withdrawal trial. First, participants received Auvelity. Those who reached a sustained clinical response were then randomly assigned either to continue Auvelity or to switch to placebo. The main outcome was how long it took for agitation symptoms to return, also called relapse.

People who continued taking Auvelity had a significantly longer time before relapse than people switched to placebo, the FDA said. Because this study enrolled people who had already responded to Auvelity, its result is especially relevant to whether continued treatment may help maintain a response. It does not, on its own, show how likely all people with Alzheimer’s-related agitation are to respond initially.

The FDA announcement does not report the length of follow-up in the withdrawal study. It also does not describe participants’ ages, Alzheimer’s disease severity, other health conditions, or demographic characteristics. Those missing details limit what can be concluded about longer-term use and how broadly the findings apply.

Like other medicines, Auvelity has risks. The most commonly reported side effects listed by the FDA are dizziness, upset stomach, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction, and uncontrolled sweating.

Auvelity also has a boxed warning, the FDA’s most prominent warning, about an increased risk of suicidal thoughts and behaviors in adolescents and young adults taking antidepressants. The FDA says health care providers should monitor for clinical worsening and new suicidal thoughts or behaviors, particularly when treatment begins.

The medicine can cause seizures, with risk increasing at higher doses. It can also raise blood pressure and may trigger mania or hypomania in people who are susceptible. Mania and hypomania are periods of unusually elevated or irritable mood and increased energy. Before treatment, the FDA says clinicians should assess blood pressure, screen for a personal or family history of bipolar disorder, and check whether a person takes other products containing bupropion or dextromethorphan.

The FDA granted the application breakthrough therapy and priority review designations, programs intended to speed review of certain medicines. The approval was granted to Axsome Therapeutics. Further publicly reported trial details and longer-term evidence would help clarify the size and durability of benefit, as well as which patients are most likely to benefit safely.