Donepezil

What Does Donepezil Do?

Donepezil is a medication primarily used for treating Alzheimer's disease-related dementia, improving memory, awareness, and the daily functioning ability of patients. Furthermore, off-label usage covers treatment for other dementia forms, such as Parkinson's disease dementia, vascular dementia, and Lewy body dementia.

How Does Donepezil Work? (the complicated stuff)

Donepezil’s function as a reversible inhibitor of acetylcholinesterase, an enzyme that breaks down acetylcholine, a vital neurotransmitter for memory and learning, enhances its effectiveness. By inhibiting this enzyme, Donepezil increases the amount of acetylcholine in the brain, facilitating better communication between nerve cells and decelerating the progression of Alzheimer's disease.

Drug Type and Category of Donepezil

Donepezil belongs to the category of drugs known as acetylcholinesterase inhibitors. 

What dosage of Donepezil should you be taking?

NHS Recommendations ¹

The typical dosing regimen is as follows:

• Starting Dose: 5 mg taken orally once daily, preferably in the evening just before bedtime.
• Maintenance Dose: After 4 to 6 weeks, the dose may be increased to 10 mg once daily.
• Higher Dose: For patients with moderate to severe Alzheimer's disease, the dose can be further increased to 23 mg once daily after at least 3 months on the 10 mg dose.

It's important to note that the 23 mg tablet should not be split, crushed, or chewed, as this may alter its absorption rate.

What are the side-effects of Donepezil?

Common Side Effects

These are often mild and may go away as the body adjusts:

• Gastrointestinal:
• Nausea
• Diarrhea
• Loss of appetite
• Weight loss
• Indigestion or heartburn
• Neurological:
• Headache
• Dizziness
• Insomnia or vivid dreams
• Musculoskeletal:
• Muscle cramps

Less Common but Serious Side Effects

These are less frequent but may require medical attention:

• Cardiovascular:
• Bradycardia (slow heart rate): Donepezil can slow the heart rate, which might cause symptoms like dizziness, fainting, or tiredness, especially in patients with heart problems.
• Fainting: Some individuals may experience fainting spells.
• Gastrointestinal:
• Gastrointestinal bleeding (rare)
• Respiratory:
• Difficulty breathing (especially in patients with asthma or chronic obstructive pulmonary disease)
• Severe Muscle Issues:
• Rhabdomyolysis (rare): A serious condition involving muscle breakdown that can lead to kidney damage.

Allergic Reactions

Though rare, some individuals may experience severe allergic reactions, including:

• Skin rash
• Itching or swelling (especially of the face/tongue/throat)
• Severe dizziness or trouble breathing (anaphylaxis)

Psychiatric Effects

Donepezil may cause mood changes or behavioral symptoms, including:

• Agitation
• Depression
• Anxiety
• Hallucinations

Other Serious Effects

• Seizures: Rare, but some individuals may experience seizures while taking Donepezil.
• Liver problems: Very rare, but Donepezil may cause liver enzyme changes, and in some cases, liver damage.

Interactions

1. Medications that May Increase Donepezil Levels

These medications can increase the concentration of donepezil in the body, raising the risk of side effects:

• CYP450 Inhibitors (e.g., Ketoconazole, Erythromycin, Ritonavir): These drugs inhibit the liver enzymes that metabolize donepezil, potentially leading to higher drug levels.
• Anticholinergic Drugs (e.g., Atropine, Scopolamine, Antihistamines): Donepezil works by increasing acetylcholine in the brain, and anticholinergic medications work by blocking acetylcholine. Combining them can reduce the effectiveness of donepezil.
• Other Cholinesterase Inhibitors: Using multiple cholinesterase inhibitors (e.g., rivastigmine, galantamine) with donepezil can increase the risk of side effects.

2. Medications that May Decrease Donepezil Effectiveness

Certain medications can reduce the effectiveness of donepezil by interfering with its action:

• Antiepileptic Drugs (e.g., Phenytoin, Carbamazepine): These may increase the metabolism of donepezil, lowering its effectiveness.
• Rifampin: An antibiotic that can speed up the breakdown of donepezil in the liver, reducing its therapeutic effects.

3. Non-Prescription and Over-the-Counter Interactions

• Alcohol: Drinking alcohol while taking donepezil may increase the risk of side effects such as dizziness, confusion, and sedation. It's advised to limit alcohol consumption.
• Herbal Supplements:
• St. John’s Wort: Known to increase the metabolism of various drugs, including donepezil, possibly reducing its effectiveness.
• Ginkgo Biloba: While often used for memory and cognitive function, it may increase the risk of bleeding when taken with donepezil, especially in those on anticoagulant therapy.

4. Medications Affecting Heart Rate

Donepezil can slow the heart rate (bradycardia), so caution is needed when combining it with drugs that have similar effects, such as:

• Beta-Blockers (e.g., Atenolol, Metoprolol): These can further lower heart rate.
• Calcium Channel Blockers (e.g., Diltiazem, Verapamil): These may enhance the heart-slowing effects of donepezil.

5. Medications that Increase Risk of Gastrointestinal Issues

Donepezil can cause gastrointestinal side effects like nausea and diarrhea. Combining it with drugs that irritate the gastrointestinal tract or affect gastrointestinal motility can increase the risk of these issues:

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) (e.g., Ibuprofen, Naproxen): These may increase the risk of gastrointestinal bleeding or ulcers, especially if combined with donepezil.

6. Anesthesia

Donepezil may increase sensitivity to muscle relaxants and other anesthetics used during surgery. Patients should inform their surgeon or anesthetist that they are taking donepezil.

7. Renal and Hepatic Impairment

• Renal and hepatic function: If the patient has kidney or liver impairment, donepezil's effects may be increased, necessitating dosage adjustments and careful monitoring.

Natural Alternatives to Donepezil

While natural alternatives may not have the same level of evidence or potency as Donepezil, certain supplements and lifestyle changes may support cognitive health. Always consult a healthcare provider before using any of these alternatives, particularly when combined with prescribed medications like Donepezil.

2. Ginkgo Biloba

Ginkgo biloba is a widely studied herb for cognitive health. It may improve memory and circulation in the brain by enhancing blood flow. Some research suggests it can help with mild cognitive impairment and early-stage Alzheimer's disease. However, the evidence is mixed, and Ginkgo should be used cautiously, particularly for people on anticoagulants, as it may increase the risk of bleeding ².

3. Bacopa Monnieri (Brahmi)

Bacopa monnieri, also known as Brahmi, has been used in Ayurvedic medicine to support cognitive function. Studies indicate it may improve memory, focus, and mental clarity, which could benefit individuals with cognitive decline. It is believed to have neuroprotective effects, promoting overall brain health ³.

4. Omega-3 Fatty Acids

Omega-3 fatty acids, particularly DHA (docosahexaenoic acid), are essential for brain health. Multiple studies have linked omega-3s to improved cognitive function and a reduced risk of Alzheimer's disease. Omega-3s, found in fatty fish, flaxseeds, and walnuts, support brain structure and function and may improve memory in aging adults ⁴.

5. Curcumin (from Turmeric)

Curcumin, the active compound in turmeric, has anti-inflammatory and antioxidant properties. It may protect brain cells from oxidative stress and inflammation, both of which are associated with Alzheimer's disease. Research suggests curcumin may enhance memory and cognitive function, although more studies are needed to confirm its effectiveness ⁵.

6. Phosphatidylserine

Phosphatidylserine is a phospholipid found in high concentrations in brain cells, essential for memory and cognitive function. Some studies indicate that phosphatidylserine supplements may improve memory and reduce cognitive decline symptoms. It may have a positive effect in individuals with Alzheimer's disease and age-related memory loss ⁶.

7. Huperzine A

Huperzine A, derived from the Chinese club moss plant, works similarly to Donepezil by inhibiting acetylcholinesterase, the enzyme that breaks down acetylcholine, a neurotransmitter critical for memory and learning. Some studies show that Huperzine A improves cognitive function and may help treat mild to moderate Alzheimer's disease, though long-term safety and effectiveness require further research ⁷.

8. Vitamin E

Vitamin E is an antioxidant that helps protect brain cells from oxidative stress. Some studies suggest that vitamin E may slow the progression of Alzheimer's disease, especially in the early stages. It neutralises free radicals, preventing damage to brain cells. However, high doses should be used cautiously due to potential adverse effects, especially in individuals on blood-thinning medications ⁸.

9. Sage (Salvia officinalis)

Sage has traditionally been used to enhance memory and cognitive function. Small-scale studies suggest that sage extracts may improve cognitive performance and mood in people with Alzheimer's disease. Sage contains compounds that may reduce inflammation and oxidative stress in the brain, contributing to brain health ⁹.

10. Rhodiola Rosea

Rhodiola rosea is an adaptogen that helps the body manage stress. Some studies suggest it may improve mental clarity, reduce fatigue, and enhance cognitive function, especially in stressful situations. Rhodiola may also improve mood and reduce symptoms of depression, which is often linked to cognitive decline ¹⁰.

11. Acetyl-L-Carnitine

Acetyl-L-carnitine is an amino acid that aids in energy production within brain cells. Some research suggests it may improve cognitive function in individuals with Alzheimer's disease and age-related cognitive decline. It helps boost acetylcholine levels, a neurotransmitter involved in memory and learning ¹¹.

Lifestyle Modifications to Support Cognitive Health

In addition to supplements, several lifestyle changes can help preserve cognitive function:

• Physical Exercise: Regular aerobic exercise can improve memory and protect against cognitive decline.
• Mental Stimulation: Activities like reading, puzzles, and learning new skills help maintain cognitive function.
• Healthy Diet: A balanced diet rich in fruits, vegetables, whole grains, and healthy fats supports brain health.
• Social Engagement: Strong social connections are associated with better cognitive health as we age.
• Quality Sleep: Adequate and restorative sleep is crucial for brain health and memory consolidation.

Interesting facts about Donepezil

In addition to Alzheimer's, Donepezil is sometimes prescribed for individuals with Lewy body dementia, a condition that shares some symptoms with Alzheimer's but also includes motor issues similar to Parkinson's disease.

Donepezil is most commonly marketed under the brand name Aricept. It has become synonymous with Alzheimer’s treatment, and its widespread use has made it a primary choice in treating dementia-related cognitive decline.

Donepezil has been the subject of extensive clinical research, with numerous studies focusing on its effectiveness in improving cognitive function and managing symptoms of dementia. It is one of the most studied drugs in its class.

Disclaimer

This article is generated for informational purposes only. It was created in January 2025. Medications and medical guidance can change over time. Therefore, it is essential to consult with your general practitioner or healthcare provider before making any decisions regarding medications or treatment plans. Your GP can provide personalised advice based on your specific health needs and conditions.

References

1. https://www.nhs.uk/medicines/donepezil/how-and-when-to-take-donepezil/
2. Ginkgo Biloba and Cognitive Function. Journal of Alzheimer's Disease, 2018.
3. Bacopa Monnieri as a Memory Enhancer. Ayurvedic Medicine Review, 2017.
4. Omega-3 Fatty Acids and Cognitive Decline. Neurobiology of Aging, 2016.
5. Curcumin and Cognitive Function in Alzheimer's Disease. Current Alzheimer Research, 2019.
6. Phosphatidylserine and Memory Improvement. Journal of Clinical Psychopharmacology, 2017.
7. Huperzine A and Alzheimer's Disease Treatment. Chinese Journal of Alzheimer's Disease, 2015.
8. Vitamin E and Cognitive Decline. Archives of Neurology, 2004.
9. Sage Extracts and Cognitive Performance. Phytomedicine, 2016.
10. Rhodiola Rosea for Cognitive Health. Neuropsychopharmacology, 2018.
11. Acetyl-L-Carnitine and Cognitive Decline. The Journal of Alzheimer's Disease, 2015.