Agitation is a common and challenging symptom in Alzheimer's disease, characterized by restlessness, emotional distress, and aggressive behaviors. Managing these symptoms is crucial for improving the quality of life for both patients and caregivers.

As of May 2023, the U.S. Food and Drug Administration (FDA) has approved brexpiprazole (Rexulti) as the first and only treatment specifically indicated for agitation associated with dementia due to Alzheimer's disease. No other approved treatment is available.

Axsome Therapeutics recently announced they plan to file for approval of their product containing dextromethorphan and bupropion, Auvelity. This combination is already approved for migraines. A combination with dextromethorphan may sound familiar; in addition to cough syrup formulations, a treatment for pseudobulbar affect was marketed several years ago as “Nuedexta” (Dextromethorphan / Quinidine).

Dextromethorphan's modulation of serotonin and norepinephrine pathways contributes to its potential in managing agitation by improving emotional stability. In combination with bupropion the bioavailability of dextromethorphan is increased significantly. Additionally, this combination is non-sedating and may have a quicker onset of action compared to an antipsychotic. Supporters of this combination speak to the importance of treating agitation without an antipsychotic. The burden of regulations in long term care continue to make treatment with an antipsychotic challenging even if it is “on label.”

The Cohen Mansfield scale was used in the pivotal studies for Rexulti (brexpiprazole) and Auvelity (bupropion/dextromethorphan). “Agitation” as a symptom is not considered a reason for treatment with any medication, and even “dementia with agitation” requires appropriate documentation, as it is not an exempt diagnosis per the Centers for Medicare Services(CMS).

Our facilities are in need of a treatment option that does not involve antipsychotics, nor anticonvulsants (like Depakote (valproate)). This new combination therapy may offer a much-needed choice, as the company recently completed studies that showed clinical efficacy in this disease state.