How I Treat: Lightening the Load for Caretakers Case Presentation

Hello, I'm Dr Leslie Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla, New York. Today we're going to talk about a case of Alzheimer agitation.

So, this is a person with Alzheimer disease who has agitation in addition to their dementia. Let's meet Ronald. He's a 71-year-old man with moderate Alzheimer disease, living with a 75-year-old spouse. Ronald cannot be safely left alone at home. Someone always has to be with him. A home health aide comes in 3 days a week for respite and for Ronald’s spouse to go shopping and attend to her own medical appointments. Unfortunately, Ronald has become more agitated, at times escalating to verbal aggression and, on occasion, striking out at the home health aid when being assisted with bathing. In the past week, Ronald appeared to not recognize his spouse at times.

And agitation in Alzheimer dementia is a very bad prognostic sign.

It worsens the impact of an already devastating and burdensome disease. We need to take care of it. Agitation associated with Alzheimer disease is complex, stressful, and costly, and has been associated with an accelerated disease progression, functional decline, decreased quality of life, increased risk of institutionalization, and earlier death. It's also associated with very high care partner burden. So symptoms of agitation in patients with dementia can cause embarrassment and anxiety for care partners and it adds to the care partner burden in terms of how to care for your loved one at home.

Informal care partners of patients with cognitive impairment or dementia spend more than 20 additional hours per week actively helping patients with clinically significant agitation. Increased care partner distress coupled with agitation can lead to institutionalization of these patients with dementia that they're trying to care for. So their loved one becomes unable to be cared for at home. 

This could be part of care rejection or rejection of care that patients with Alzheimer disease sometimes display. Resistance with bathing or taking medicines or eating and so on; agitation needs to be addressed. Now it's important to distinguish psychosis from agitation.

Agitation can be associated with psychosis and that's something we sometimes confuse these— 2 different entities. People though can be psychotic and not agitated. And of course, people who are agitated can be non-psychotic.

So we need to be wary of this and be careful of this, because the treatments that we're going to be talking about are addressing the agitation in particular. Psychosis is just one of the many potential causes of agitation in Alzheimer disease. There's also that rejection of care that I brought up before.

Resistance to care. The person may not be psychotic, per se, but may not understand what is being offered to them in terms of food or medication or simply bathing. 

So question number 2 for us to think about is, after ruling out a delirium, what treatments may help Ronald? Haloperidol, lorazepam, sertraline, valproate, all of the above? Well, in the past, all of the above were considered because that's all we had.

If we think about the pharmacological treatments of the past, they included all sorts of different psychotropic agents. And we knew that behavioral symptoms required us to think about the various treatments. But also, what about these treatments that may be offered actually lead to complications behaviorally? Up until 2023, there were no treatments specifically approved by the FDA for behavioral disturbances associated with dementia.

There has been some evidence in the literature suggesting efficacy limited, however, regarding the use of antidepressants, antipsychotics, anxiolytics, and mood stabilizers. Amongst the antipsychotics, they all have black box warnings related to elderly demented patients with psychosis. Nevertheless, risperidone was approved for behavioral and psychological symptoms of dementia in Australia, Canada, the UK, and New Zealand, but not in the US.

We've used other antipsychotics as well, particularly haloperidol. Keep in mind, some of the medicines that have been used can actually harm a patient. So, for example, anxiolytics, benzodiazepines are not optimal, to say the least, in patients who are elderly. Selection of any medication should be based on clinical experience, circumstances, and physician judgment, and thus we did use these agents. The overall approach that we generally adhere to is “start low and go slow” and consider the multitude of drug-drug interactions that can occur.

And, of course, periodic assessment for benefit and risk is critical. Things have changed, though.

Here's another question: Which of the following agents are FDA-approved for the treatment of agitation associated with Alzheimer dementia? Risperidone? Pimavanserin? Dexmedetomidine sublingual film? or Brexpiprazole? As I read these out, I have already mentioned risperidone as being approved in some countries for this, but not in the US.

And you may have heard of pimavanserin as a treatment for Parkinson's disease psychosis. And you may have heard of dexmedetomidine sublingual film as a treatment of agitation associated with schizophrenia and bipolar disorder. You may have heard of Brexpiprazole as a treatment for schizophrenia and as an adjunctive agent for major depressive disorder.

It actually is now approved for agitation associated with Alzheimer dementia. 

So, this is what's new for 2024.

Brexpiprazole, a second-generation antipsychotic, was approved May 10, 2023 for treatment of agitation associated with dementia due to Alzheimer's disease. This is the first FDA-approved treatment option for this indication, and coming up, perhaps soon, are 2 new options.

BXCL501 dexmedetomidine sublingual film, an alpha 2 adrenergic receptor agonist, is already approved for agitation with schizophrenia and bipolar disorder and may be approved for Alzheimer's disease agitation as an as-needed medicine. Not approved yet but maybe in the future. 

Lastly, there's AXS05, Dextromethorphan/Bupropion combination.

You may be aware of it as a first-line treatment for major depressive disorder. It is currently in clinical trials to determine its utility in agitation associated with Alzheimer disease. 

BXCL501 sublingual dexmedetomidine achieved breakthrough therapy designation for the potential use in agitation associated with Alzheimer disease. It is approved, as I mentioned, for schizophrenia or bipolar 1 or 2 disorder in adults as a treatment for agitation associated with those entities and there are clinical trials in progress regarding this perhaps new indication in the future for dexmedetomidine. 

Lastly, AXS-05 Dextromethorphan/Bupropion combination also got breakthrough therapy designation and reported our 2 trials. One was an acute trial, the other one was a maintenance trial and there is a third trial underway looking at the acute use of Dextromethorphan/Bupropion combination. 

We need to think about these treatments, though, as part of a comprehensive management plan.

We need to consider the continuation of use of non-pharmacological interventions in addition to whatever medicines we offer. We need to collaborate and communicate with the caregivers and also provide them with information about peer-based support networks. Also provide counseling. This is very helpful in terms of making sure people can remain at home for as long as possible and not be unduly institutionalized prematurely. 

Guidelines for a Comprehensive Management Plan

1. Differential diagnosis: Careful evaluation and treatment for general medical, psychiatric, environmental, or psychosocial problems that may underlie the disturbance
2. Nonpharmacological intervention: If agitation does not cause significant danger or distress to the patient or others, symptoms are best treated with environmental or behavioral measures, including:

• Behavioral management therapy or behavioral interventions
• Emotion-oriented approaches
• Stimulation-oriented treatments (recreational activity, art therapy, music therapy, and pet therapy)

      3. Pharmacological intervention: If nonpharmacological measures are unsuccessful or behaviors are dangerous or distressing, then judicious pharmacological intervention is recommended:

• Antipsychotics are the pharmacological therapy recommended by the APA for agitation in dementia
• The Harvard South Shore Program also recommends antipsychotics for more than moderately disruptive agitation

So, let me summarize for you, Alzheimer dementia takes a massive toll on our society with respect to psychological and physical impairments, quality of life, and impact on loved ones, and agitation makes it worse, and it's not rare.

Alzheimer disease caregivers, particularly of those patients with agitation, are at great risk of their own mental health issues, such as anxiety and depression. We have some new solutions or some assistance we can provide. Brexpiprazole all is a newly approved option for the treatment of agitation associated with Alzheimer's disease. Additional non-antipsychotic options in late stage of clinical development include Dextromethorphan/Bupropion combination for daily use and Dexmedetomidine sublingual film for PRN use with both agents presently commercially available for other indications. 

I hope you found this useful and I look forward to speaking with you again.

© 2024 HMP Global. All Rights Reserved.
 
Any views and opinions expressed above are those of the author(s) and do not necessarily reflect the views, policy, or position of the Psych Congress Network or HMP Global, their employees, and affiliates.