What are the initial treatment options for dementia, specifically Alzheimer's disease, in terms of medications like cholinesterase inhibitors (e.g. donepezil) and memantine?

From the Guidelines

Initial treatment for Alzheimer's disease typically involves cholinesterase inhibitors like donepezil, rivastigmine, or galantamine for mild to moderate disease, with memantine added for moderate to severe cases. Donepezil is often the first choice, starting at 5mg once daily for 4-6 weeks, then increasing to 10mg daily if tolerated, as recommended by the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia 1. These medications work by increasing acetylcholine levels in the brain, which helps improve cognitive function by enhancing neural communication. Memantine, which regulates glutamate activity, is typically started at 5mg daily and gradually increased to 10mg twice daily. While these medications cannot stop disease progression, they can temporarily improve symptoms or slow decline for 6-12 months in some patients. Common side effects include nausea, vomiting, and diarrhea for cholinesterase inhibitors, and dizziness and confusion for memantine. Treatment should be accompanied by regular monitoring of cognitive function and reassessment every 6 months to evaluate continued benefit, as suggested by the American College of Physicians and the American Academy of Family Physicians 1. Non-pharmacological approaches like cognitive stimulation, physical activity, and caregiver support are equally important components of comprehensive dementia care. Some key points to consider when treating dementia include:

• The decision to initiate therapy should be based on evaluation of benefits and risks associated with an individual patient 1.
• The choice of pharmacologic agents should be based on tolerability, adverse effect profile, ease of use, and cost of medication 1.
• There is no convincing evidence that one therapeutic treatment is more effective than another 1.
• The duration of trials in most cases was less than 1 year, and evidence is insufficient to determine the optimal duration of therapy 1. However, the most recent and highest quality study, the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia 1, provides the most up-to-date guidance on the treatment of dementia.

From the FDA Drug Label

Memantine and donepezil hydrochlorides extended-release capsules are a combination of memantine hydrochloride, an NMDA receptor antagonist, and donepezil hydrochloride, an acetylcholinesterase inhibitor, indicated for the treatment of moderate to severe dementia of the Alzheimer’s type in patients stabilized on 10 mg of donepezil hydrochloride once daily The recommended starting dose of memantine and donepezil hydrochlorides extended-release capsules is 7 mg/10 mg, taken once daily in the evening. The dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg/10 mg.

The initial treatment options for dementia, specifically Alzheimer's disease, include cholinesterase inhibitors like donepezil and memantine.

• Donepezil is an acetylcholinesterase inhibitor that can be used alone or in combination with memantine, an NMDA receptor antagonist.
• The recommended starting dose for the combination of memantine and donepezil hydrochlorides extended-release capsules is 7 mg/10 mg, taken once daily in the evening, with a recommended maintenance dose of 28 mg/10 mg 2.
• Patients on donepezil hydrochloride 10 mg only can start with 7 mg/10 mg of the combination, while those already on memantine hydrochloride (10 mg twice daily or 28 mg extended-release once daily) and donepezil hydrochloride 10 mg can be switched to 28 mg/10 mg of the combination 2.

From the Research

Initial Treatment Options for Dementia

The initial treatment options for dementia, specifically Alzheimer's disease, include medications such as cholinesterase inhibitors (e.g., donepezil) and memantine.

• Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate Alzheimer's disease 3.
• Memantine, a glutamate antagonist, is licensed for moderate to severe dementia in Alzheimer's disease, but its use is not recommended by the England and Wales National Institute for Health and Clinical Excellence 4.

Efficacy of Cholinesterase Inhibitors

Cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, have been shown to be efficacious for mild to moderate Alzheimer's disease, improving cognitive function, activities of daily living, and behavioral disturbances 3.

• Donepezil, in particular, has been found to improve cognition and global clinical function in patients with mild to moderate Alzheimer's disease, with beneficial effects on activities of daily living and caregiver burden 5.

Combination Therapy with Memantine

The addition of memantine to a treatment regimen that already includes a cholinesterase inhibitor, such as donepezil, may provide additional benefits in patients with moderate-to-severe Alzheimer's disease 6, 7.

• A fixed-dose combination of memantine extended-release and donepezil has been approved for the treatment of moderate-to-severe Alzheimer's disease, offering a simpler treatment regimen and potential advantages in terms of adherence and persistence 7.

Adverse Events and Tolerability

Cholinesterase inhibitors, such as donepezil, are generally well-tolerated, with most adverse events being mild and transient, although the incidence of adverse events is higher with these medications compared to placebo 3, 5.

• Memantine, when added to a cholinesterase inhibitor, may be associated with a higher risk of adverse events, such as vomiting, syncope, and weight loss 7.