Is it worth initiating Donepezil (Aricept) or Memantine (Namenda) for late-stage dementia?

From the Guidelines

Starting Aricept (donepezil) or Namenda (memantine) for late-stage dementia generally offers limited benefit and may not be worth initiating at this advanced stage. These medications provide modest symptomatic improvements at best in late dementia, with studies showing minimal impact on cognitive function, daily activities, or quality of life at this stage 1. The evidence suggests that the benefits of these medications, although statistically significant, are not clinically significant for cognition and are modest for global assessments 1.

Key Considerations

• The effectiveness of donepezil and memantine diminishes as dementia progresses and more brain cells are lost.
• Side effects like nausea, dizziness, confusion, and headaches may outweigh potential benefits.
• If the person is already taking these medications, abrupt discontinuation should be avoided; instead, discuss a gradual tapering plan with their healthcare provider 1.
• At this stage, focusing on comfort care, managing behavioral symptoms, maintaining dignity, and supporting caregivers often provides more meaningful benefits than medication.

Decision Making

Any decision to initiate or continue these medications should involve the patient's healthcare team, considering the individual's overall health status, other medications, and goals of care 1. The decision to initiate therapy should be based on an evaluation of benefits and risks associated with an individual patient, taking into account the potential for modest or no benefit and the known adverse events associated with these medications 1.

Prioritizing Care

In late-stage dementia, prioritizing comfort care, managing behavioral symptoms, and supporting caregivers is often more beneficial than medication 1. This approach focuses on maintaining the patient's dignity and quality of life, rather than solely pursuing pharmacologic interventions with limited benefits.

From the FDA Drug Label

Study 1 (Twenty-Eight-Week Study) In a study of 28 weeks duration, 252 patients with moderate to severe probable Alzheimer’s disease (diagnosed by DSM-IV and NINCDS-ADRDA criteria, with Mini-Mental State Examination scores ≥ 3 and ≤ 14 and Global Deterioration Scale Stages 5 to 6) were randomized to memantine hydrochloride or placebo Study 3 (Twelve-Week Study) In a double-blind study of 12 weeks duration, conducted in nursing homes in Latvia, 166 patients with dementia according to DSM-III-R, a Mini-Mental State Examination score of < 10, and Global Deterioration Scale staging of 5 to 7 were randomized to either memantine hydrochloride or placebo INDICATIONS AND USAGE Donepezil is an acetylcholinesterase inhibitor indicated for the treatment of dementia of the Alzheimer’s type. Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer’s Disease (1)

The decision to initiate Donepezil (Aricept) or Memantine (Namenda) for late-stage dementia should be made on a case-by-case basis.

• Key considerations include the patient's current condition, medical history, and potential benefits and risks of treatment.
• The studies suggest that Memantine may be effective in slowing decline in patients with moderate to severe Alzheimer's disease 2.
• Donepezil has been shown to be effective in patients with mild, moderate, and severe Alzheimer's Disease 3. However, the evidence is not conclusive, and the decision to initiate treatment should be made with caution and careful consideration of the individual patient's needs.

From the Research

Efficacy of Donepezil and Memantine in Late-Stage Dementia

• The studies 4, 5, 6, 7, 8 suggest that Donepezil and Memantine can be effective in treating moderate to severe Alzheimer's disease.
• A study published in 2024 4 found that a fixed-dose combination of donepezil and memantine (Mioreol) demonstrated clinical efficacy, safety, and good tolerability in patients with Alzheimer's disease and mixed dementia.
• Another study from 2021 5 found that both donepezil and memantine treatments produced statistically significant improvements in behavioral and psychological symptoms of dementia.

Benefits of Combination Therapy

• A 2012 study 6 found that continued treatment with donepezil was associated with cognitive benefits and significant functional benefits in patients with moderate or severe Alzheimer's disease.
• The same study 6 found that memantine treatment also provided cognitive benefits, but the efficacy of donepezil and memantine did not differ significantly in the presence or absence of the other.
• A 2011 review 7 found that adding memantine to a treatment regimen that already includes stable donepezil therapy can provide a statistically significant benefit in patients with moderate-to-severe Alzheimer's disease.

Safety and Tolerability

• The studies 4, 5, 6, 7, 8 suggest that Donepezil and Memantine are generally well-tolerated, with mostly mild and transient adverse effects.
• A 2015 review 8 found that memantine ER plus donepezil combination therapy was well tolerated, with diarrhea, dizziness, and influenza occurring at least twice as often with add-on memantine ER as add-on placebo in donepezil-treated patients.

Clinical Relevance

• While the studies suggest that Donepezil and Memantine can be effective in treating moderate to severe Alzheimer's disease, the clinical relevance of this benefit remains unclear 7.
• A 2015 review 8 found that memantine ER plus donepezil combination therapy is an effective and well-tolerated treatment option for patients with moderate to severe Alzheimer's disease, and the fixed-dose combination is potentially more convenient than coadministration of the individual agents.