Deprescribing Medications for Dementia

(IMPACT Trial)

No longer recruiting at 2 trial locations

Overseen By Anuva Fellner

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: National Institute on Aging (NIA)

Disqualifiers: Critical condition, ICU consult, Nursing facility

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach called PRIDE (also known as Aricept), which aims to reduce the use of potentially inappropriate medications in people with dementia or mild cognitive impairment. Researchers aim to determine if tracking medication changes and their effects after an emergency department visit is practical. They also seek to enhance communication between emergency department pharmacists and regular doctors to better manage medications. Individuals diagnosed with dementia or mild cognitive impairment, who have visited a Northwestern Medicine outpatient facility before, and can participate in medication reviews or have a care partner to assist, might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve medication management for dementia patients.

Will I have to stop taking my current medications?

The trial focuses on reducing certain medications that affect the central nervous system for people with dementia. It suggests that some medications might be adjusted or stopped, but it doesn't specify which ones or how. It's best to discuss your specific medications with the trial team.

What prior data suggests that the PRIDE intervention is safe for patients with dementia?

Research has shown that stopping or reducing certain medications can be safe and beneficial for people with dementia. The PRIDE approach emphasizes discontinuing medications that might be unnecessary and potentially harmful.

Studies have found that some drugs, such as anticholinergic medications, can worsen dementia symptoms. Reducing these drugs can lower risks, including falls and other side effects.

When evaluating the safety of stopping medications, each person's unique situation must be considered. The process requires careful monitoring and communication among healthcare providers to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the PRIDE treatment approach because it focuses on deprescribing potentially inappropriate medications (PIMs) for patients with dementia or mild cognitive impairment. Unlike standard treatments that may add more drugs to manage symptoms, PRIDE aims to reduce medication burden by having clinical pharmacists review and recommend stopping unnecessary central nervous system (CNS) medications. This personalized approach could lead to fewer side effects and better overall cognitive health for patients, offering a fresh perspective on managing dementia.

What evidence suggests that the PRIDE intervention is effective for deprescribing medications in dementia patients?

Research has shown that safely stopping unnecessary medications, known as deprescribing, can be effective and safe for people with dementia. In this trial, a clinical pharmacist will conduct medication reconciliation for participants in the PRIDE arm and communicate deprescribing recommendations to the outpatient prescriber. Studies emphasize the importance of reducing unnecessary medications because dementia patients are more prone to side effects. The goal is to minimize non-essential drugs, reducing risks and improving overall health. Evidence supports that deprescribing can ease the treatment burden and might lower the chances of adverse medication reactions. This approach aims to enhance the quality of life for those with dementia by avoiding unnecessary medication use. ^{2 6 7 8 9}

Who Is on the Research Team?

Scott Dresden, Dr.

Principal Investigator

Northwestern University- Department of Emergency Medicine

Are You a Good Fit for This Trial?

This trial is for people with Alzheimer's Disease and Related Dementias (ADRD) or Mild Cognitive Impairment (MCI) who visit the emergency department. It aims to see if it's possible to review their medications, reduce inappropriate ones, and improve communication between ED pharmacists and other doctors.

Inclusion Criteria

Has had prior outpatient care performed at Northwestern Medicine location(s)

Community dwelling

Able to participate in medication reconciliation as determined by the pharmacist or with a knowledgeable care partner present

Exclusion Criteria

Reside in nursing facility or assisted living facility

Emergency Severity Index (ESI) of 1 (critical)

I was referred to intensive care from the emergency department.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Emergency Department Intervention

Pharmacists perform medication reconciliation and communicate deprescribing recommendations for CNS PIMs on the day of the ED visit

1 day

1 visit (in-person)

Outpatient Follow-up

Outpatient prescribers receive a medication report and follow-up with patients who received deprescribing recommendations

90 days

Follow-up

Participants are monitored for repeat ED visits and medication supply of CNS PIMs

90 days

What Are the Treatments Tested in This Trial?

Interventions

• PRIDE

Trial Overview The PRIDE intervention is being tested to check its feasibility in the emergency setting for dementia patients. The study will look at how well medication reviews are completed, inappropriate drug use is reduced, and follow-up care is managed after an ED visit.

How Is the Trial Designed?

Group I: PRIDE Patients Experimental Treatment 1 Intervention

Community-dwelling adults (age 18+) in the ED with prior outpatient visits within the NM system and a history of dementia or mild cognitive impairment recorded in the NM EHR will be eligible for inclusion. We will include 290 patients across 3 sites to have medication reconciliation conducted by the clinical pharmacist. Patients who were previously prescribed CNS PIMs will have deprescribing recommendations communicated by the clinical pharmacist to the outpatient prescriber.

PRIDE is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Aricept for:

• Mild, moderate, and severe dementia related to Alzheimer's disease

Approved in United States as Aricept for:

• Mild, moderate, and severe dementia related to Alzheimer's disease

Approved in Canada as Aricept for:

• Mild, moderate, and severe dementia related to Alzheimer's disease

Approved in Japan as Aricept for:

• Mild, moderate, and severe dementia related to Alzheimer's disease

Who Is Running the Clinical Trial?

National Institute on Aging (NIA)

Lead Sponsor

Trials

1,841

Recruited

28,150,000+

Brown University

Collaborator

Trials

480

Recruited

724,000+

Published Research Related to This Trial

A national survey of 890 primary care physicians revealed that the two main barriers to deprescribing medications for older adults with moderate dementia are the perception of symptomatic benefit reported by patients or families, and the fact that the medication was prescribed by another physician.

Understanding these ethical concerns can help improve clinician education on medication management and deprescribing practices for older adults, ensuring safer and more effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethical Aspects of Physician Decision-Making for Deprescribing Among Older Adults With Dementia. Norton, JD., Zeng, C., Bayliss, EA., et al.[2023]

In a study of 46,737 Medicare beneficiaries and 29,496 Danish participants, cholinesterase inhibitors like donepezil showed similar cardiovascular safety profiles, with no significant differences in the risk of myocardial infarction (MI) or heart failure compared to other medications.

Memantine was linked to a higher risk of fatal or nonfatal MI and cardiac death in the Danish cohort, as well as increased all-cause mortality in both cohorts, suggesting that patients prescribed memantine may have been sicker overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative cardiovascular safety of dementia medications: a cross-national study. Fosbøl, EL., Peterson, ED., Holm, E., et al.[2018]

A scoping review identified 12 studies that evaluated various tools for deprescribing medications in people with severe dementia, highlighting the complexity of this task and its potential to improve patient safety and quality of life.

Despite the development of several deprescribing tools, only one study showed a clear clinical benefit from medication withdrawal, indicating a need for more evidence-based research to assess the effectiveness of these tools in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tools for deprescribing in severe dementia: A scoping review. Wang, C., Roberts, E., Smith, G., et al.[2023]

Clinical registries and electronic medical records (EMRs) allow researchers to study medication safety and effectiveness in larger, more diverse populations, including those often excluded from randomized controlled trials, which can reveal rare adverse events over longer follow-up periods.

Despite some variability in the accuracy of diagnoses in administrative data, these sources provide valuable insights into medication exposure and prescribing patterns, helping to identify risk factors and improve treatment strategies for dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using clinical registries, administrative data and electronic medical records to improve medication safety and effectiveness in dementia. Ilomäki, J., Lai, EC., Bell, JS.[2021]

A systematic review of 26 studies found that the prevalence of potentially inappropriate prescribing in older people with dementia ranges from 14% to 74%, highlighting a significant risk for adverse events in this population.

The Beers criteria were the most commonly used tool for identifying inappropriate prescriptions, but many studies did not utilize the full criteria, suggesting a need for more standardized and comprehensive application of these tools.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying potentially inappropriate prescribing in older people with dementia: a systematic review. Hukins, D., Macleod, U., Boland, JW.[2022]

A systematic review of 5 studies found that the prevalence of adverse drug events (ADEs) in older inpatients with dementia is alarmingly high at 81.5%, indicating a significant safety concern for this population.

The prevalence of adverse drug reactions (ADRs) varied between 12.7% and 24.0%, highlighting the need for better assessment methods and tailored tools to prevent these reactions in older patients with dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of adverse drug events and adverse drug reactions in hospital among older patients with dementia: A systematic review. Sakiris, MA., Sawan, M., Hilmer, SN., et al.[2021]

This pilot N-of-1 trial involving four participants over 15 weeks found no significant difference in cognitive impairment between those taking statins and those on a placebo, suggesting that statins may not adversely affect cognition in older adults with dementia.

The study highlights the difficulties in recruiting participants for deprescribing trials in dementia populations, indicating that more research is needed to explore the effects of medication discontinuation in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Feasibility of Using N-Of-1 Trials to Investigate Deprescribing in Older Adults with Dementia: A Pilot Study. Clough, AJ., Hilmer, SN., Naismith, SL., et al.[2020]

The automated targeted medication review (TMR) service successfully reduced potentially inappropriate medications (PIMs) among patients with dementia, with 11,608 TMRs leading to discontinued PIMs in 8,002 patients after four months.

Younger patients, those living in higher poverty levels, and individuals with multiple prescribers or pharmacies were more likely to benefit from the TMR service, highlighting its effectiveness in addressing PIM prescribing in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Automated Targeted Medication Review Electronic Alerts to Reduce Potentially Inappropriate Medication Prescribing Among Medicare Enrolled Patients With Dementia. Silva-Almodóvar, A., Malfara, A., Nahata, MC.[2020]

A study of 422 people with dementia revealed that 87% were willing to stop one or more of their medications, indicating a strong openness to deprescribing, which could enhance their quality of life.

Among those taking six or more medications, 29% believed they were on unnecessary medications, and 92% expressed willingness to deprescribe, suggesting that higher medication burden correlates with a desire to reduce medication use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attitudes toward deprescribing among older adults with dementia in the United States. Growdon, ME., Espejo, E., Jing, B., et al.[2023]

Deprescribing, or reducing unnecessary medications, is a recognized priority for improving the health of older adults with dementia, but there is limited direct evidence on its safety and efficacy specifically for this group.

A review of nineteen studies showed that most focused on medication-related outcomes rather than patient-centered results, highlighting a need for more comprehensive research that includes the perspectives of patients and their caregivers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of deprescribing in older adults with dementia: a narrative review. Sawan, MJ., Moga, DC., Ma, MJ., et al.[2021]

The study outlines a comprehensive five-step process for developing an intervention aimed at reducing the use of antidepressants among nursing home residents with dementia, emphasizing collaboration among GPs, nursing staff, and families.

Key themes identified during the development included the need for professional training, effective communication, and active involvement of patients and relatives, which informed the creation of a case-based training course and a structured consultation tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailoring a complex intervention to reduce antidepressants in institutionalized older persons with dementia. Hølmkjær, P., Vermehren, C., Holm, A., et al.[2023]

The revised Patients' Attitude Towards Deprescribing questionnaire for individuals with mild cognitive impairment and mild-to-moderate dementia (rPATDcog) was successfully developed and tested with 21 participants and their 11 carers.

A significant majority (81%) of participants expressed a willingness to stop one or more medications if advised by their doctor, indicating a positive attitude towards deprescribing in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and pilot testing of the revised Patients' Attitudes Towards Deprescribing questionnaire for people with cognitive impairment. Reeve, E., Anthony, AC., Kouladjian O'Donnell, L., et al.[2019]

In a study of 123 patients treated with donepezil for Alzheimer's dementia, 21% discontinued treatment due to adverse events (AEs), highlighting the need for careful monitoring during the initial months of therapy.

The most common AEs leading to discontinuation were nausea/vomiting, diarrhea, and loss of appetite, indicating that these side effects are significant considerations in the management of patients on donepezil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse events causing discontinuation of donepezil for Alzheimer's dementia]. Carøe, TK., Moe, C.[2018]

Citations

1. withpower.com withpower.com/trial/phase-emergencies-2-2024-2fba0

Deprescribing Medications for Dementia (IMPACT Trial) The research highlights the importance of reducing inappropriate medications in dementia patients, suggesting that deprescribing can be safe and feasible.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10961769/

Deprescribing in Older Poly-Treated Patients Affected with ... Polypharmacy is an important issue in older patients affected by dementia because they are very vulnerable to the side effects of drugs.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11577138/

Discontinuation of Cholinesterase Inhibitors Following ... Discontinuing cholinesterase inhibitors when initiating memantine in patients with dementia may be reasonable to reduce treatment burden, costs, and the risk ...

4. researchgate.net researchgate.net/publication/278454871_A_Randomized_Double-Blind_Placebo-Controlled_Study_of_the_Efficacy_and_Safety_of_Donepezil_in_Patients_with_Alzheimer's_Disease_in_the_Nursing_Home_Setting

A Randomized, Double-Blind, Placebo-Controlled Study of ... CONCLUSION: Patients treated with donepezil maintained or improved in cognition and overall dementia severity in contrast to placebo‐treated ...

5. researchgate.net researchgate.net/publication/325871952_Donepezil_for_dementia_due_to_Alzheimer's_disease

Donepezil for dementia due to Alzheimer's disease Adverse events reported were consistent with the known cholinergic effects of donepezil and with the safety profile in patients with mild to moderate AD.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8802736/

CCCDTD5 recommendations on the deprescribing of ... The decision to deprescribe cognitive enhancers must consider each patient's preferences, treatment indications, current clinical status and symptoms, ...

7. mdpi.com mdpi.com/2308-3417/9/2/28

Deprescribing in Older Poly-Treated Patients Affected with ... Anticholinergic drugs can dramatically worsen the cognitive deterioration of dementia patients. In addition, a recent study showed that the high ...

8. uptodate.com uptodate.com/contents/deprescribing

Deprescribing - UpToDate Common goals for deprescribing include reducing overall medication burden, reducing the risk of specific geriatric syndromes such as falls and ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1884556/

The safety and tolerability of donepezil in patients with ... Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.