Does a Pill Really Make a Difference?

Rexulti Approved for Agitation due to Dementia of Alzheimer’s type: A conversation between Dr. Al Power, MD, and Denise Hyde, PharmD

This article is written by Denise Hyde, a Pharmacist dedicated to person-directed care and well-being for all at The Eden Alternative, and Dr. Al Power, a Geriatrician and Author committed to person-directed dementia care & well-being.

Research

Denise Hyde photo

Denise: Despite having FDA approval, Rexulti (brexpiprazole) has a black box warning of a higher risk of death for someone living with dementia if they are taking these types of drugs due to the side effects. Brexpiprazole can cause:

  • Cerebrovascular problems like stroke, which can lead to death.
  • Neuroleptic malignant syndrome is a serious side effect that can lead to death.
  • Tardive dyskinesia which appears as uncontrollable body movements.
  • Metabolism changes that can lead to diabetes, increased cholesterol levels, and lower white blood cell count.
  • Decreased blood pressure, dizziness, and drowsiness which leads to an increased risk of falls.
  • An increased risk of seizures.
Dr. Al Power photo

Dr. Power: Rexulti is no different from other 2nd generation antipsychotics as far as the reported benefits and side effects. The difference is that when the previous 2nd generation antipsychotics were released, the FDA said “no” to their approval for use in individuals living with dementia and added the black box warning. While the FDA can say that there will be secondary drug studies once the drug has been released, they do not require it. Once the drug is approved, it will be prescribed regardless of the extra warnings.

“We think we have done something to make things better, but does this really meet the person’s actual need(s)?”

Denise: Research was done on post-marketing testing of drugs. The statistics used in the research are from 2009 to 2012 and they are sobering. Almost all post-marketing research is done to either expand the indications of an approved drug or expand the population that can take the drug. When it comes to drug research it is important to remember that most drug studies are either done by, or funded by, the drug companies trying to get their drug approved. The National Institutes of Health (NIH) is the next largest funder of drug trials. There are 3 recent studies of brexpiprazole on the NIH website, ClinicalTrials.gov. It is difficult to know if these were the studies the FDA panel reviewed or not. It is estimated that in the US right now there are 6.7 million people over the age of 65 that are living with Alzheimer’s dementia. Yet the 3 recent studies noted at ClinicalTrial.gov only show a total of 919 people that received either brexpiprazole or a placebo for the purpose of reducing agitation due to Alzheimer’s dementia. We are now applying the experience of less than 919 people to the 6.7 million people that could potentially receive this drug.

Dr. Power: There was an article in the New York Times from January 2023 about re-labeling people in order to justify the use of antipsychotics in nursing homes. The data from US nursing homes indicates that 1 out of 9 people in nursing homes have a diagnosis of schizophrenia. The incidence is 1 out of every 150 in the general population. At the age of 80, can you suddenly develop a condition that generally appears at a much younger age and with strong genetic ties? We have to be careful about using the term schizophrenia or psychosis for people living with dementia. These are people who are misinterpreting their surroundings, who are trying to fill in missing information the best way that they can through their deficits, they are people who have needs they cannot express, who are then becoming distressed and we are labeling it schizophrenia. As well-intentioned people, we see a behavior that we think looks like someone who is psychotic and we give the person a pill that makes them quieter. We think we have done something to make things better, but does this really meet the person’s actual need(s)?

“While on the surface it appears that giving this drug will reduce the stress on the employee care partners, it will actually increase their workload with the additional assessments and documentation.”

Approval

Denise: It is also important to note that brexpiprazole is not for prn (as needed) use.

Dr. Power: I personally do not favor prn use with these medications for three reasons:

  1. They are often given after the fact, when the episode has largely resolved
  2. It decreases critical thinking about root causes when you can simply give a prn pill
  3. The side effect profile remains basically as problematic as it is with scheduled therapy

Denise: Without prn use, it means the drug has to be administered every day. As an antipsychotic, administering this medication conflicts with CMS regulations in place since at least 2012 which push for lowering the use of psychoactive drugs for residents living with dementia. CMS has provided grant funding to help states and organizations reduce the use of antipsychotics. Under CMS regulations, administering brexpiprazole means gradual dosage reductions have to be attempted every 6 months, documenting the purpose for its use, and daily documentation regarding potential side effects. With gradual dosage reductions, if the underlying cause of the agitation has not been identified and dealt with, the reduction is not going to be beneficial. While on the surface it appears that giving this drug will reduce the stress on the employee care partners, it will actually increase their workload with the additional assessments and documentation. What happens for the person living with dementia taking this at home?

“There has never been a study of antipsychotics that shows positive outcomes, improved markers of well-being, people that engage more, and that are happier.”

Dr. Power: The studies the FDA reviewed used the Cohen-Mansfield Agitation Inventory (CMAI) which is a common test used in research. It is a 30-year-old test, that like others used with dementia, only measures the negative expressions or effects of deficits. The goal of the research is to decrease the negative expressions, but just reducing negative effects isn’t the whole picture. There has never been a study of antipsychotics that shows positive outcomes, improved markers of well-being, people that engage more, and that are happier. It just shows that they are quieter. We have seen over and over again that when antipsychotics are removed, even for those who don’t appear sedated, they start engaging in ways they had not done before the drug. Beyond sedation, there are adverse cognitive consequences that you cannot easily measure.

I always ask people how they would feel if every time they went to their supervisor and complained about something their supervisor sedated them. How would they feel about that? Does that really solve your issue or just make the supervisor’s life a little easier? Now that may sound cruel to say these drugs are used for convenience, yet in task-based care systems, good caring people are forced into task-based care processes. Without the resources to understand and determine people’s deeper needs, they are forced into providing medication first. With Covid, the isolation, short staffing, staff turnover and a lack of trained staff the urge to medicate has multiplied. This was the perfect time to get this drug approved because it looks like an impossible situation. What does it say about our system when the solution to such a stressed and underfunded system is to sedate the most vulnerable people within the system? What does it say to our solution to the problems we have in long-term care?

This approval was inevitable. I never fooled myself that I was going to change the mindset around BPSD in the larger world. It’s just too big of a medical, industrial, and political complex working on profit and on time and task to keep the institutions running smoothly.  Institutions are like steamrollers for frail individuals who have needs.

  • Empower

“So, we know you can take care of people without giving them drugs if you have the right environment, the right staff, the right knowledge, the right kinds of care partner interactions, and the right operations.”

Does a pill really make a difference?

Dr. Power: There is plenty to criticize when it comes to the research and the approval process. The bigger question is, “Do you need any pill for people living with dementia who are exhibiting different forms of distress or personal expressions that we don’t understand?” I have reviewed the antipsychotic usage data for every state from CMS. At any given time, there are 200 US nursing homes that use 0% antipsychotics and there are hundreds more that use 3% or less. So, we know you can take care of people without giving them drugs if you have the right environment, the right staff, the right knowledge, the right kinds of care partner interactions, and the right operations. They may not all be the culture change stars but they’ve figured something out. They have decided that medications are not the answer and they’ve come to a solution. So, we know it can be done.

I am working on a book with Jennifer Carson and Pat Sprigg and we are going to quote a 30-year-old study that showed when they unlocked the door of a closed memory care area, the behavioral distress dropped by significant amounts, even more than with any antipsychotic drug.

Angela Norman has an organization in Arkansas called Meaningful Approach Consulting. They have been working with 92 nursing homes (41% of the homes) across the state for the last few years. Angela’s team provides presentations about well-being. They have modified my Well-Being Approach that is taught in the Dementia Beyond Drugs Training from Eden. They are teaching the well-being approach as a care planning tool and a decoding distress tool. They provide hotline consultations and give support. These homes were able to reduce antipsychotic use to an average of 6.7% by 2019, which was less than half of the national average. With their efforts, Arkansas has gone from 47th in the country in their use of antipsychotics to 11th between 2015 and today. I talked to Angela in the last couple of months and these homes have maintained their 6.7% average usage through the pandemic. There was no increase in antipsychotic usage. The homes showed a 74% decrease in acute or neuropsychiatric hospitalizations. The solutions are out there. There is no study of drugs, or other interventions, that has shown the level of success that this team in Arkansas has done. Most importantly, they are doing this using the Eden Alternative Well-Being approach!

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