Donepezil For Alzheimer's Disease: What to Know

While there is no cure for Alzheimer’s disease (AD) currently, two types of medications are approved to either affect the disease progression in the early stage of Alzheimer’s disease or to temporarily alleviate some of the symptoms caused by AD-associated dementia.

Cholinesterase inhibitors are a group of medications belonging to the second treatment approach mentioned above; more specifically, these medications are prescribed to treat the symptoms of cognitive decline, such as problems with memory, thought processes, judgment, and language. Even though cholinesterase inhibitors do not reverse the disease progression and improve cognitive function in AD patients, these medications can have a positive effect on their daily lives.

Continue reading to learn more about donepezil treatment for Alzheimer's disease, including the potential side effects, drug interactions, and certain risk factors.

What is Alzheimer's Disease?

Alzheimer’s disease is a progressive neurological disorder that targets memory, behavior, and thinking ability in older adults. However, it can also occur in individuals in their 30s and 40s. When Alzheimer’s disease occurs in those younger than 65 years, it is called early-onset (or younger-onset) Alzheimer’s.

Alzheimer’s is a progressive brain condition, meaning it gets worse with time. The exact cause of Alzheimer’s Disease is unknown. However, scientists believe that a protein called beta-amyloid is associated with the progression of Alzheimer’s disease. Beta-amyloid clumps together to form plaques that eventually build up into groups of a few pieces. These clumps of beta-amyloid block the communication between nerve cells. The symptoms of cognitive decline in Alzheimer’s patients are the result of this blockage.

Besides beta-amyloid, another protein called tau forms twisted strands called tangles. Plaques and tangles spread as the disease progresses. Brain cells shrink and eventually die. Disease progression typically results in the need for regular care and support. In addition to blocking nerve cell communication, beta-amyloid plaques can activate the immune system, leading to inflammation and destruction of disabled brain cells.

There are different stages of Alzheimer’s. Disease progression happens over time.

During the earlier stage, a person may experience forgetfulness and memory lapses in recent events. However, these cognitive challenges do not significantly impact their ability to engage in daily activities. The various stages of Alzheimer’s disease are as follows:

Mild Cognitive Impairment: In this stage, though a person can work independently, he or she experiences difficulty in planning or organizing, recalling names or words, confusion, and memory lapses. Mild cognitive impairment is typically noticeable only to those close to the affected individual.
Mild to Moderate Alzheimer's disease: This stage is considered the most prolonged and can last many years. A person with mild to moderate Alzheimer’s disease needs assistance to perform daily activities. He or she may get frustrated and confused and find it difficult to find the right words. During this stage, the symptoms of dementia are more prominent due to the damage of nerve cells within the brain.
Severe Alzheimer's disease: Severe Alzheimer’s disease is characterized by a profound loss of awareness, changes in physical abilities, including challenges with mobility, such as walking, sitting, and eating, as well as a sharp decline in mental processes, leading to confusion and communication difficulties. During this stage, a person may reach a point where he becomes completely bedridden and experiences severe dementia symptoms.

Taking donepezil for Alzheimer's disease

Donepezil belongs to the class of medications called cholinesterase inhibitors, which are the approved medications for the treatment of Alzheimer’s disease. While donepezil does not slow the rate of disease progression, donepezil’s cost-effectiveness makes it one of the most commonly prescribed options to treat Alzheimer’s associated dementia.

Donepezil temporarily improves cognitive decline and the quality of daily living for people with Alzheimer's disease. While it does not cure the disease, it can lessen dementia symptoms, allowing a patient to perform certain daily tasks independently for longer. The effectiveness of donepezil differs among people, depending on the disease stage and other medical conditions.

What are cholinesterase inhibitors?

Cholinesterase inhibitors are used to manage Alzheimer's disease and other types of dementia. Donepezil, rivastigmine, and galantamine are members of a class of medications called cholinesterase inhibitors. Cholinesterase is an enzyme that breaks down acetylcholine, a natural chemical that plays crucial roles in thought processes, memory, language, and judgment. By blocking cholinesterase enzymes in the brain, cholinesterase inhibitors boost the amount of acetylcholine in the brain. While cholinesterase inhibitors cannot cure Alzheimer's disease, they can temporarily improve cognitive abilities by providing symptomatic treatment.

Patients with dementia, including Alzheimer’s disease, suffer from significant memory loss, confusion, personality changes, and difficulties with communication. As a result, relationships and other aspects of work and personal life are affected as the disease progresses.

One of the main causes of severe dementia is Alzheimer’s disease. Donepezil treatment reduces dementia symptoms while temporarily improving cognitive function.

How does donepezil treat dementia?

Donepezil prevents the breakdown of acetylcholine in the brains of dementia patients and those with Alzheimer's disease. As a result, donepezil helps restore the balance of the natural neurotransmitter acetylcholine.

As mentioned, the neurotransmitter acetylcholine is involved in learning and memory. Acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine increase acetylcholine levels, temporarily improving cognitive function and alleviating the symptoms of dementia.

What is the recommended dose for donepezil treatment?

The U.S. Food and Drug Administration (FDA) approved donepezil (Aricept) for Alzheimer’s patients of different stages. The recommended donepezil dosage for mild to moderate AD is 5 milligrams (mg) or 10 mg by mouth once daily. For moderate to severe AD, the recommended donepezil dosage is 10 mg or 23 mg by mouth once daily.

Outside of the U.S., donepezil also holds an important role in the treatment of Alzheimer’s. The National Institute for Health and Clinical Excellence (NICE) in England issued guidance that recommended the utilization of donepezil for treating mild and moderate Alzheimer's disease.

Once you tolerate the 5-mg dose for 4 to 6 weeks, your doctor may increase the dose to 10 mg once daily, or the 23-mg dose can be prescribed if you have been on the 10-mg dose for 4 to 6 weeks.

Your doctor may recommend taking donepezil before going to bed, as it can cause dizziness. Donepezil can be taken with or without food.

What are the side effects and adverse events of donepezil?

Common side effects from taking donepezil include nausea, vomiting, diarrhea and loss of appetite, weight loss, headache, dizziness, muscle cramps, and daytime sleepiness. Side effects should subside as your body starts to adjust to taking donepezil. However, if side effects persist after several weeks, talk to your doctor about changing your dose or switching to a different medication.

Donepezil is typically a safe drug, but clinical trials have shown that the most common adverse events from taking donepezil include abnormal liver function, severe indigestion and stomach pain, gastrointestinal bleeding, slow heartbeat, seizures, shortness of breath, and urinary incontinence.

Unusual or allergic reactions

Although rare, an unusual or allergic reaction can occur after taking donepezil. Signs of an allergic reaction include a rash, hives, or swelling of the face, lips, tongue, or throat. If the patient experiences any symptoms of allergic reactions, seek medical attention promptly.

Drug Interactions

Certain drug interactions can change or reduce the effectiveness of donepezil or of other medications taken along with donepezil. It is important to discuss a patient's medication history with the healthcare practitioner. Taking the following drugs while receiving donepezil treatment may lead to potential side effects in Alzheimer’s disease patients:

Anticholinergic drugs (Antihistamines, antidepressants, Antipsychotics)
Cholinergic agonists (bethanechol)
NSAID (ibuprofen, naproxen)
Warfarin or anticoagulants
CYP3A4 enzyme system inducers and inhibitors (rifampicin, ketoconazole)
Cimetidine (for Ulcers, Gastroesophageal reflux disease GERD)
Antidepressants (fluoxetine, paroxetine)
Antifungal drugs (fluconazole, itraconazole)
Phenobarbital, Phenytoin, Carbamazepine

How do you measure cognitive performance on donepezil?

Several methods are used to monitor the cognitive performance of patients receiving donepezil treatment as well as untreated patients who are not receiving any current treatment. Some of the most common tactics include:

Monitoring behavioral symptoms and daily life

Monitoring behavioral symptoms like anger, aggression, and depression is a useful way to evaluate Alzheimer’s disease progression. Talking to the patient, family members, and friends about any changes in behavior, personality, or mental abilities, as well as their medical history and other medications they have taken currently or in the past.

Cognitive function and behavioral tests

There are a range of tests that can be conducted to evaluate a person’s cognitive function, mental abilities, and dementia symptoms. These tests can be done regularly to assess any significant differences in cognitive function, any significant memory loss, or other unwanted effects of dementia or Alzheimer’s disease progression. Examples of cognitive performance tests include:

Montreal Cognitive Assessment (MMSE)
Clinical Dementia Rating Sum
Alzheimer’s Disease Assessment Scale - Cognitive Subscale
Clock Drawing Test
Trail Making Test
Functional Assessment
Brain Imaging (MRI, PET, SPECT)
Biomarker Assessment
Mini-Mental State Examination
Neuropsychiatric Inventory
Severe Impairment Battery

What if I miss a dose of donepezil?

To ensure the continuity of treatment, it’s crucial that the patient strictly adheres to the dosing schedule prescribed by the healthcare provider in order to get the desired results.

Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take a double dose or extra medicine to make up for a missed dose.

If more than one dose is missed, the patient should seek medical attention immediately. Continue the medication as the doctor tells you to.

What precautions should I take while on donepezil?

Rarely, donepezil can cause an unusual or allergic reaction. Tell your provider if you have had allergic reactions in the past to donepezil.

Check with your healthcare provider before taking any other over-the-counter medicines, prescription medications, or alternative treatments. Drug interactions between donepezil and your other medications can affect how the medicines work or cause serious adverse events.

Tell your doctor if you are pregnant or breastfeeding. More data is needed regarding donepezil’s effects on pregnant women and breast milk.

Inform your healthcare provider of any history of cardiac issues, seizures, gastrointestinal diseases, or if you have liver disease.

Donepezil is metabolized by the liver so it is necessary to regularly monitor patients with liver diseases and adjust dosing for effectiveness and safety.

Avoid driving a vehicle or operating any machinery, as donepezil can cause dizziness.

What are donepezil patches?

Along with donepezil tablets, there are also donepezil patches available. Donepezil patches are marketed as Adlarity and are approved by the FDA. The patches are applied to the buttocks, thighs, or back, and they deliver the drug transdermally (through the skin).

Donepezil patches are available in two strengths:

Low dose: 5 mg/ day
High dose: 10 mg/ day

The transdermal delivery system is considered an alternative to the oral drug delivery system for those at an increased risk of forgetting their pills or who have difficulty swallowing. The usual start dose for donepezil patch is to apply one 5-mg patch onto the skin once weekly. Our doctor may increase the dose to one 10-mg patch once weekly after you have been on the 5-mg patch for 4 to 6 weeks.

When to seek medical attention

While cholinesterase inhibitors provide a symptomatic treatment to slow down the disease progression, Alzheimer’s disease has no cure. While taking donepezil, be aware of the side effects, interactions, and adverse events that can occur. If you experience any of the following adverse events or unwanted effects, tell your doctor immediately.

Severe nausea, vomiting, diarrhea, or skin rashes
Hives, difficulty breathing, swelling of the face, lips, tongue, or throat
Slow heartbeat, dizziness, fainting, chest pain, or shortness of breath
Increased confusion, aggression, agitation, or hallucinations.
Increased memory loss, difficulty with daily living and activities, or significant changes in behavior

Remember that open communication with your healthcare provider is essential throughout your donepezil treatment. They can provide guidance, monitor your progress, and make necessary adjustments to your treatment plan to ensure the best possible outcome in managing Alzheimer's disease.

If dementia symptoms worsen to severe Alzheimer’s disease, your doctor may recommend other medicines and may also talk about nursing home placement to help patients and their loved ones with daily living and care.

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