Deprescribing for Dementia
(R2D2 Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen byNoll 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.
12345Is 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.
14678How 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.
1491011Eligibility 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
+2 more
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.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Active Intervention (ACT)Experimental Treatment1 Intervention
Pharmacist-based Deprescribing
Group II: Usual Care (UC)Placebo Group1 Intervention
Usual Care
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Indiana University HealthIndianapolis, IN
Eskenazi HealthIndianapolis, IN
Community Health Network Foundation, Inc.Indianapolis, IN
Loading ...
Who Is Running the Clinical Trial?
Indiana UniversityLead Sponsor
National Institute on Aging (NIA)Collaborator
References
Anticholinergic co-prescribing in nursing home residents using cholinesterase inhibitors: Potential deprescribing cascade. [2023]Polypharmacy may result from inappropriate prescribing of medications to treat adverse drug reactions (ADRs), i.e., "prescribing cascade." A potentially harmful prescribing cascade affecting those with severe dementia can result when anticholinergics are prescribed to manage side effects of cholinesterase inhibitors (ChEIs). We investigated 1) factors associated with co-prescribing of anticholinergics and ChEIs and 2) whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics-a potentially beneficial reversal or "deprescribing cascade."
Effect of anticholinergic burden on treatment modification, delirium and mortality in newly diagnosed dementia patients starting a cholinesterase inhibitor: A population-based study. [2022]Few studies have evaluated the association between anticholinergic burden and treatment modification after starting a cholinesterase inhibitor in clinical practice. We aimed to evaluate the effect of anticholinergic burden on anti-dementia treatment modification, delirium and mortality. We retrospectively analysed older adults (n = 25 825) who started a cholinesterase inhibitor during 2003-2011 from Korean National Health Insurance Service Senior Cohort Database. High anticholinergic burden was defined as an average daily Anticholinergic Cognitive Burden (ACB) score of >3 during the first 3 months. We investigated the impact of high anticholinergic burden on the rate of treatment modification, delirium and mortality in comparison with minimal ACB (ACB score ≤1) in propensity-matched cohorts (N = 7438). Approximately 6.0% of patients with dementia were exposed to a high anticholinergic burden within the first three months of treatment. In high anticholinergic burden cohorts, significantly more patients experienced treatment modification (34.9% vs. 32.1%) or delirium (5.6% vs. 3.6%) and the mortality rate was also higher (16.8% vs. 14.1%) than controls. A multivariate Cox proportional hazard regression analysis showed that an average ACB score >3 within the first three months significantly increased the risk of treatment modification (hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.02-1.24), delirium (HR: 1.52, CI: 1.17-1.96) and mortality (HR: 1.23, CI: 1.06-1.41). This study showed that high anticholinergic burden negatively affected the treatment response to cholinesterase inhibitors and that an average ACB score >3 was an independent prognostic factor for delirium or mortality in dementia patients.
Anticholinergic Drug Burden in Persons with Dementia Taking a Cholinesterase Inhibitor: The Effect of Multiple Physicians. [2021]To explore the association between the number of physicians providing care and anticholinergic drug burden in older persons newly initiated on cholinesterase inhibitor therapy for the management of dementia.
Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia. [2023]Medications with anticholinergic properties are commonly prescribed to older adults with a pre-existing diagnosis of dementia or cognitive impairment. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden because of its potential to cause adverse effects. It is possible that a high anticholinergic burden may be a risk factor for further cognitive decline or neuropsychiatric disturbances in people with dementia. Neuropsychiatric disturbances are the most frequent complication of dementia that require hospitalisation, accounting for almost half of admissions; hence, identification of modifiable prognostic factors for these outcomes is crucial. There are various scales available to measure anticholinergic burden but agreement between them is often poor.
The use of medications with known or potential anticholinergic activity in patients with dementia receiving cholinesterase inhibitors. [2006]To assess the prevalence of prescribed medications with anticholinergic activity given concurrently with acetylcholinesterase-inhibitor therapy in long-term care residents with dementia and to recommend dose adjustment or discontinuation of these medications with anticholinergic activity.
Anticholinergic medicines use among older adults before and after initiating dementia medicines. [2021]We investigated anticholinergic medicines use among older adults initiating dementia medicines.
Factors Associated With Deprescribing Acetylcholinesterase Inhibitors in Older Nursing Home Residents With Severe Dementia. [2020]Uncertainty regarding benefits and risks associated with acetylcholinesterase inhibitors (AChEIs) in severe dementia means providers do not know if and when to deprescribe. We sought to identify which patient-, provider-, and system-level characteristics are associated with AChEI discontinuation.
Anticholinergic burden (prognostic factor) for prediction of dementia or cognitive decline in older adults with no known cognitive syndrome. [2022]Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the 'anticholinergic burden' because of its potential to cause adverse effects. It is possible that high anticholinergic burden may be a risk factor for development of cognitive decline or dementia. There are various scales available to measure anticholinergic burden but agreement between them is often poor.
Anticholinergic Drug Exposure and the Risk of Dementia: There Is Modest Evidence for an Association but Not for Causality. [2020]Many observational studies published during the past 15 years have found an association between anticholinergic drug exposure and the risk of incident dementia. Animal data suggest plausible causal mechanisms for this finding. The results of a recent, large, and well-conducted study on the subject were widely disseminated by the lay and scientific media. This study addressed protopathic bias by examining anticholinergic drug exposure in time windows 1-11, 3-13, and 5-20 years before the identification of dementia. In brief, the study found that, pooling anticholinergic drug exposure across 11 drug categories, exposure in smallest to largest cumulative dosing groups was significantly associated with incident dementia risk, with an apparently dose-dependent relationship in unadjusted as well as adjusted analyses in all time windows prior to dementia identification. Whereas these findings appear compelling, there are at least 4 elephants in the room. First, only 3 of 11 anticholinergic drug categories were consistently associated with an increased risk of dementia; this suggests that anticholinergic activity may be an irrelevant common denominator. Second, for 2 of these 3 categories (antidepressant and antipsychotic drugs), confounding by indication seemed a distinct possibility. Third, in many analyses it seemed that exposure for as little as the equivalent of 1-90 days sufficed to increase the risk of dementia at a time interval of up to 20 years later; a causal mechanism here would need to have strong neurotoxic effects to result in the widespread brain changes that characterize dementia. Finally, the associations were almost uniformly stronger for vascular dementia than for Alzheimer's disease, making the identification of a causal mechanism even more challenging. Deprescribing anticholinergics to reduce state-dependent cognitive impairment, or to reduce the risk of delirium in vulnerable demographic and medical populations, is reasonable. Deprescribing anticholinergics to reduce the risk of future dementia is presently unwarranted.
Tolerability of Cholinesterase Inhibitors: A Population-Based Study of Persistence, Adherence, and Switching. [2018]Cholinesterase inhibitors (ChEIs) are prescribed to dementia patients despite their poor tolerance. Low tolerability potentially reduces persistence and adherence, while inducing switching between medications. Comparisons of these utilization measures contribute to knowledge of the relative tolerability of these medications.
Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study. [2022]Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission.