Treatment for Agitation in Alzheimer Dementia: Pipeline Preview with George Grossberg, MD

"It's a very rich pipeline because it's a very common and very debilitating symptom in Alzheimer's disease."

Agitation is one of the most common symptoms observed in adults with Alzheimer disease, and one of the most challenging to manage, George Grossberg, MD, the Samuel W Fordyce professor and director of Geriatric Psychiatry at Saint Louis University School of Medicine, told Patient Care® editors in a recent interview. Depending on the setting and on the stage of disease, he continued, research suggests that a "minimum of 50% of patients are affected by the spectrum of agitated behaviors."

When medication becomes required, the traditional choices have been limited to off-label use of treatments for psychotic behavior as well as the minor tranquilizers, including benzodiazepines. Grossberg explained that currently there is only 1 drug approved by the FDA to treat the spectrum of behavioral symptoms, ie, brexpiprazole (Rexulti, Otsuka). However, there is another one nearing final approval by the FDA (AXS-05; Axsome) and, as geriatric psychiatrist Grossberg highlights in the short video above, the pipeline is "very rich." He provides a range of examples.

The following transcript has been edited for clarity and style.

Patient Care: Would you talk about some of the investigational medications for Alzheimer's agitation in the research pipeline?

George Grossberg, MD. Dexmedetomidine might be familiar to our audience because it’s been available for a number of years, but only as an intravenous (IV) formulation. It has been widely used in intensive care units parenterally to quickly calm patients. However, as you can imagine, an IV drug is far from ideal for an ambulatory Alzheimer’s patient who is experiencing psychomotor agitation. It’s a challenge to get a patient in that state to sit still for an IV line—let alone the time it takes to administer the infusion.

About 5 o5 6 years ago, the company that manufactures dexmedetomidine developed an oral form. It’s essentially a wafer that can be placed under the tongue or anywhere in the buccal cavity. Unlike other treatments being used for agitation, this formulation works quickly, often within 60 minutes or less—90 minutes at most. So it is an excellent option for situations requiring acute management, such as in emergency departments or hospital settings where a patient is displaying overtly aggressive behavior. That said, it has not been approved yet in that form.

Beyond dexmedetomidine, there are several cannabinoids being explored in the pipeline. We are going to be doing a large multicenter trial with investigators from the UK who have developed a proprietary form of CBD, the non-hallucinogenic component of cannabis, to alleviate agitation in Alzheimer’s dementia patients. And there’s also nabilone, a synthetic cannabinoid, being evaluated and prazosin is showing promise, too.

Unfortunately, some other attempts have been less successful. For example, a deuterated form of dextromethorphan-quinidine recently reported negative trial results.

Overall, it's a very rich pipeline because it's a very common and very debilitating symptom in Alzheimer's disease.

George T Grossberg, MD, is the Samuel W. Fordyce professor and director of Geriatric Psychiatry in the Department of Psychiatry at Saint Louis University School of Medicine. He is a past president of the American Association for Geriatric Psychiatry and of the International Psychogeriatric Association. Grossberg's research focus includes behavioral symptoms in Alzheimer disease and novel therapies for neurocognitive disorders.