Deprescribing for Dementia

(R2D2 Trial)

Not currently recruiting at 2 trial locations

Overseen By Noll L Campbell, PharmD, MS

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Must be taking: Anticholinergics

Must not be taking: Alzheimer's medications

Disqualifiers: Nursing home, Schizophrenia, Bipolar, Alzheimer's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether reducing certain medications, specifically anticholinergics (which can affect the brain), improves thinking and safety for people at risk of dementia. Participants will either receive assistance from a pharmacist to decrease these medications (deprescribing of target anticholinergics) or continue their usual care without changes. Ideal participants are aged 65 or older, have recently taken these medications, and have regular visits with their primary care doctor. As an unphased trial, this study offers participants the chance to contribute to important research that could enhance dementia care and medication safety.

Will I have to stop taking my current medications?

The trial focuses on reducing the use of certain anticholinergic medications, so you may need to stop or reduce these specific drugs. The protocol does not specify if you must stop other medications.

Will I have to stop taking my current medications?

The trial focuses on reducing the use of certain anticholinergic medications, so you may need to stop or reduce these specific medications. The protocol does not specify if you must stop other medications.

What prior data suggests that this deprescribing intervention is safe for dementia patients?

Research has shown that stopping anticholinergic medications can lower the risk of memory and thinking problems. Anticholinergics, which can harm brain function, pose a particular risk to older adults. Studies suggest that reducing these drugs may help prevent issues with memory and thinking.

Some studies found that stopping these medications led to reduced use and better outcomes. However, other research did not find a clear effect on factors like falls or quality of life. Results can vary, and some studies were short-term.

Overall, stopping anticholinergics appears safe and might benefit brain health. However, effects can depend on individual health and specific medications. Prospective trial participants should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about deprescribing target anticholinergics for dementia because it offers a fresh approach to managing the condition. Unlike standard treatments, which often focus on adding medications to manage symptoms, this method aims to safely reduce or eliminate certain medications that might worsen cognitive issues. By focusing on pharmacist-led deprescribing, this approach has the potential to minimize side effects and improve overall cognitive function in patients. This strategy represents a shift from conventional practices, emphasizing personalized care and reducing medication burden.

What evidence suggests that this trial's treatments could be effective for dementia?

This trial will compare two approaches: the Active Intervention (ACT), which involves pharmacist-based deprescribing of anticholinergic medications, and Usual Care (UC). Research has shown that reducing anticholinergic medications might help prevent or slow memory and thinking problems. These medications can affect brain function, so reducing them might improve cognitive skills. Some studies suggest potential benefits, but results are mixed, and strong evidence of clear improvements in memory, fall prevention, or quality of life is lacking. More research is needed to confirm these effects and to identify safe methods for reducing these medications. ^{1 2 4 5 6}

Who Is on the Research Team?

Noll L Campbell, PharmD, MS

Principal Investigator

Indiana University/Purdue University

Are You a Good Fit for This Trial?

This trial is for people aged 65 or older who have seen their primary care doctor in the past year, are currently using certain anticholinergic medications known to affect memory, can speak English, and have a phone. It's not for those living in nursing homes or with schizophrenia, bipolar disorder, Alzheimer's Disease or related dementias.

Inclusion Criteria

Able to communicate in English

I have seen my primary care doctor in the last year.

Access to a telephone

Exclusion Criteria

Permanent resident of an extended care facility (nursing home)

I have been diagnosed with schizophrenia, bipolar disorder, or schizoaffective disorder.

I have been diagnosed with Alzheimer's or a similar type of dementia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants receive a pharmacist-based deprescribing intervention or usual care

24 months

Visits at baseline, 6, 12, 18, and 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deprescribing of target anticholinergics
• Usual Care

Trial Overview

The study tests if stopping the use of specific anticholinergic drugs (deprescribing) can improve cognitive function compared to usual care without deprescribing. Participants will be grouped by their healthcare provider and randomly assigned to either continue usual care or start the deprescribing process.

How Is the Trial Designed?

Group I: Active Intervention (ACT) Experimental Treatment 1 Intervention

Pharmacist-based Deprescribing

Group II: Usual Care (UC) Placebo Group 1 Intervention

Usual Care

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

A recent large study found a significant association between anticholinergic drug exposure and the risk of developing dementia, suggesting a dose-dependent relationship, but only three out of eleven drug categories consistently showed this link.

Despite the findings, the evidence does not support deprescribing anticholinergics solely to prevent future dementia, as confounding factors and the need for strong neurotoxic mechanisms raise questions about causality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticholinergic Drug Exposure and the Risk of Dementia: There Is Modest Evidence for an Association but Not for Causality. Andrade, C.[2020]

In a study of Medicare beneficiaries aged 65 and older with severe dementia, 15% were found to be co-prescribed anticholinergics alongside cholinesterase inhibitors (ChEIs), indicating a potential prescribing cascade that could lead to harmful effects.

Discontinuing ChEIs was associated with a significantly lower likelihood of stopping anticholinergic medications, suggesting that reversing this prescribing cascade is challenging and highlighting the need for better deprescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticholinergic co-prescribing in nursing home residents using cholinesterase inhibitors: Potential deprescribing cascade. Gromek, KR., Thorpe, CT., Aspinall, SL., et al.[2023]

In a study of 25,825 older adults starting cholinesterase inhibitors, 6% had a high anticholinergic burden, which was linked to a higher rate of treatment modifications (34.9% vs. 32.1%) and increased instances of delirium (5.6% vs. 3.6%).

An average Anticholinergic Cognitive Burden (ACB) score greater than 3 within the first three months significantly raised the risk of treatment modification, delirium, and mortality, indicating that high anticholinergic burden is a serious concern for dementia patients on these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of anticholinergic burden on treatment modification, delirium and mortality in newly diagnosed dementia patients starting a cholinesterase inhibitor: A population-based study. Ah, YM., Suh, Y., Jun, K., et al.[2022]

In a study of 37,106 nursing home residents aged 65 and older with severe dementia, nearly 30% discontinued acetylcholinesterase inhibitors (AChEIs) within a year, highlighting the uncertainty around their long-term use in this population.

Factors such as new admissions, older age, and certain health conditions increased the likelihood of discontinuation, while the use of memantine and strong anticholinergics decreased the likelihood, suggesting complex interactions that influence treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated With Deprescribing Acetylcholinesterase Inhibitors in Older Nursing Home Residents With Severe Dementia. Niznik, JD., Zhao, X., He, M., et al.[2020]

In a study of 2,021 long-term care residents, 20.7% of those receiving acetylcholinesterase inhibitors were also prescribed medications with anticholinergic activity, which can potentially interfere with the effectiveness of their dementia treatment.

Only 16.4% of cases resulted in recommended changes to anticholinergic medications, highlighting a need for healthcare providers to carefully evaluate the risks versus benefits of these medications in patients with cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of medications with known or potential anticholinergic activity in patients with dementia receiving cholinesterase inhibitors. Mann, JL., Evans, TS., Taylor, RD., et al.[2006]

In a study of over 91,000 older adults newly prescribed cholinesterase inhibitors for dementia, it was found that seeing more physicians was linked to a higher risk of anticholinergic drug burden, with a 24% increase in odds for every five additional doctors consulted.

While community-dwelling seniors showed a clear association between multiple physicians and increased anticholinergic burden, this link was not statistically significant for those in long-term care, highlighting the need for better communication among healthcare providers to manage medication risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticholinergic Drug Burden in Persons with Dementia Taking a Cholinesterase Inhibitor: The Effect of Multiple Physicians. Reppas-Rindlisbacher, CE., Fischer, HD., Fung, K., et al.[2021]

In a review of 18 studies involving 102,684 older adults, a significant anticholinergic burden was associated with an increased risk of mortality, with a hazard ratio of 1.153 for those with high anticholinergic scores compared to those with minimal scores.

While 40% of studies indicated a potential link between anticholinergic burden and greater long-term cognitive decline, the overall evidence was of low certainty, and no definitive conclusions could be made regarding its impact on neuropsychiatric disturbances, physical function, or institutionalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia. Taylor-Rowan, M., Kraia, O., Kolliopoulou, C., et al.[2023]

In a study of dementia patients using British Columbia claims data, galantamine showed the best tolerability with longer persistence and better adherence compared to donepezil, indicating it may be a more favorable option for patients.

Rivastigmine, particularly the oral form, had the shortest persistence and highest switching rates, while the rivastigmine patch reduced discontinuation but was associated with poorer adherence compared to the oral formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Cholinesterase Inhibitors: A Population-Based Study of Persistence, Adherence, and Switching. Fisher, A., Carney, G., Bassett, K., et al.[2018]

About one-third of older adults starting dementia medications were also prescribed anticholinergic medicines, which can have harmful effects, highlighting a potential safety concern in this vulnerable population.

The use of antipsychotics, particularly risperidone, increased significantly after initiating dementia treatments, indicating a trend towards more complex medication regimens that may complicate patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticholinergic medicines use among older adults before and after initiating dementia medicines. Narayan, SW., Pearson, SA., Litchfield, M., et al.[2021]

A systematic review of 25 studies involving 968,428 older adults suggests that a higher anticholinergic burden is associated with an increased risk of cognitive decline or dementia, with an odds ratio of 2.63 for those with significant anticholinergic effects.

The Anticholinergic Cognitive Burden scale (ACB scale) was particularly highlighted, showing that as the severity of anticholinergic burden increases, so does the risk of cognitive decline, indicating a potential need for careful medication management in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticholinergic burden (prognostic factor) for prediction of dementia or cognitive decline in older adults with no known cognitive syndrome. Taylor-Rowan, M., Edwards, S., Noel-Storr, AH., et al.[2022]

In a study of 352 dementia patients across 17 UK hospitals, it was found that a significant percentage of patients (43.2%) were discharged with an increased anticholinergic burden, indicating a potential risk for worsening cognitive function.

Notably, 44.9% of patients taking cholinesterase inhibitors, the main treatment for dementia, were also prescribed anticholinergic medications, which could counteract the benefits of their dementia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study. Hook, A., Randall, JL., Grubb, CM., et al.[2022]

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