Deprescribing Medications for Dementia

(IMPACT Trial)

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

290 Participants Needed

Trial Summary

What is the purpose of this trial?

Aim 1: To demonstrate the feasibility by determining proportion of completed medication reconciliation, Central Nervous System active Potentially Inappropriate Medication (CNS PIM) use among patients with Alzheimer's Disease and Related Dementias (ADRD) and Mild Cognitive Impairment (MCI) in the emergency department (ED), and communication between ED clinical pharmacists and outpatient prescribers. Aim 2: To demonstrate the feasibility of collecting the primary and secondary outcomes for a subsequent study. The future primary outcome will be reduction in CNS PIMs 90 days after an ED visit. Secondary outcomes will include outpatient follow-up, repeat ED visits, and hospitalizations during the 90 days following an ED visit. Aim 3: To demonstrate the acceptability of the PRIDE intervention to outpatient clinicians using the Acceptability of Intervention Measure and qualitative analysis of responses.

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 data supports the effectiveness of the drug PRIDE, Aricept for deprescribing medications in dementia?

The research highlights the importance of reducing inappropriate medications in dementia patients, suggesting that deprescribing can be safe and feasible. Although specific data on PRIDE, Aricept is not provided, the studies emphasize the potential benefits of deprescribing in improving quality of life for dementia patients. ^{1 2 3 4 5}

Is deprescribing medications for dementia safe for humans?

Research shows that medications for dementia, like donepezil, can have adverse events (unwanted side effects) that sometimes lead to stopping the treatment. Studies also compare the heart safety of dementia drugs, and older people with dementia are at risk of adverse events from inappropriate prescribing. ^{6 7 8 9 10}

How does the drug PRIDE (Aricept) differ from other treatments for dementia?

PRIDE (Aricept) is unique because it focuses on deprescribing, which means reducing or stopping medications that may not be necessary or could be harmful, especially in older adults with dementia. This approach is different from other treatments that typically involve adding medications to manage symptoms. ^{3 4 11 12 13}

Research Team

Scott Dresden, Dr.

Principal Investigator

Northwestern University- Department of Emergency Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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 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]

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 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]

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]

References

1. United States 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. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Feasibility of Using N-Of-1 Trials to Investigate Deprescribing in Older Adults with Dementia: A Pilot Study. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Tailoring a complex intervention to reduce antidepressants in institutionalized older persons with dementia. [2023]

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

Ethical Aspects of Physician Decision-Making for Deprescribing Among Older Adults With Dementia. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Tools for deprescribing in severe dementia: A scoping review. [2023]

6. Denmark pubmed.ncbi.nlm.nih.gov

[Adverse events causing discontinuation of donepezil for Alzheimer's dementia]. [2018]

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

Using clinical registries, administrative data and electronic medical records to improve medication safety and effectiveness in dementia. [2021]

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

Comparative cardiovascular safety of dementia medications: a cross-national study. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

Identifying potentially inappropriate prescribing in older people with dementia: a systematic review. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Prevalence of adverse drug events and adverse drug reactions in hospital among older patients with dementia: A systematic review. [2021]

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

The value of deprescribing in older adults with dementia: a narrative review. [2021]

12. Australia pubmed.ncbi.nlm.nih.gov

Development and pilot testing of the revised Patients' Attitudes Towards Deprescribing questionnaire for people with cognitive impairment. [2019]

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

Attitudes toward deprescribing among older adults with dementia in the United States. [2023]