Deprescribing for Dementia

(R2D2 Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Noll L Campbell, PharmD, MS

Age: 65+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: Indiana University

Must be taking: Anticholinergics

Must not be taking: Alzheimer's medications

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

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

A cluster-randomized controlled trial (RCT) called "Reducing Risk of Dementia through Deprescribing" (R2D2) to evaluate the impact of a deprescribing intervention on important cognitive and safety outcomes.

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.

What data supports the effectiveness of deprescribing anticholinergic medications for dementia?

Research suggests that reducing anticholinergic medications in dementia patients can be beneficial, as a high anticholinergic burden is linked to worse treatment outcomes, increased delirium, and higher mortality rates. Deprescribing these medications may help improve cognitive function and reduce the risk of adverse effects. ^{1 2 3 4 5}

Is deprescribing anticholinergic medications safe for people with dementia?

Deprescribing anticholinergic medications, which are often used in older adults with dementia, can be safe and may help reduce the risk of further cognitive decline or neuropsychiatric issues. Reducing the use of these medications can lower the 'anticholinergic burden' (the combined effect of all anticholinergic medications a person takes), which is linked to adverse effects. ^{1 4 6 7 8}

How is the deprescribing of anticholinergic drugs unique for dementia treatment?

Deprescribing anticholinergic drugs for dementia is unique because it focuses on reducing the overall anticholinergic burden, which may help minimize cognitive decline and neuropsychiatric symptoms, unlike other treatments that add medications. This approach is different from standard treatments that often involve prescribing additional drugs, potentially leading to a prescribing cascade. ^{1 4 9 10 11}

Research Team

Noll L Campbell, PharmD, MS

Principal Investigator

Indiana University/Purdue University

Eligibility Criteria

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.

Treatment Details

Interventions

• Deprescribing of target anticholinergics (Other)
• Usual Care (Other)

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.

Participant Groups

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+

Alan Palkowitz

Indiana University

Chief Executive Officer since 2020

PhD in Chemistry from Indiana University

David Ingram

Indiana University

Chief Medical Officer since 2020

MD from Indiana University School of Medicine

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

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 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 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]

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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Anticholinergic co-prescribing in nursing home residents using cholinesterase inhibitors: Potential deprescribing cascade. [2023]

2. England 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Anticholinergic Drug Burden in Persons with Dementia Taking a Cholinesterase Inhibitor: The Effect of Multiple Physicians. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The use of medications with known or potential anticholinergic activity in patients with dementia receiving cholinesterase inhibitors. [2006]

6. England pubmed.ncbi.nlm.nih.gov

Anticholinergic medicines use among older adults before and after initiating dementia medicines. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Factors Associated With Deprescribing Acetylcholinesterase Inhibitors in Older Nursing Home Residents With Severe Dementia. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Anticholinergic burden (prognostic factor) for prediction of dementia or cognitive decline in older adults with no known cognitive syndrome. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

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

10. New Zealand pubmed.ncbi.nlm.nih.gov

Tolerability of Cholinesterase Inhibitors: A Population-Based Study of Persistence, Adherence, and Switching. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study. [2022]