Do Donepezil and Memantine Really Help Alzheimer's Symptoms?

Donepezil and memantine can modestly help some people with Alzheimer's disease, but they do not stop or reverse it. Product labeling describes donepezil for mild to severe disease and memantine for moderate to severe disease, and the prescriber can confirm what applies to your situation. Benefits are usually small and vary a great deal from person to person, such as steadier thinking or daily function for a period. This article explains how each drug works, what to expect, common side effects, and which symptoms need urgent care.

What these two medicines are meant to do

Alzheimer's disease gradually damages brain cells and the connections between them. The MedlinePlus Alzheimer's Disease overview describes treatment as aimed at managing symptoms, and current medicines can help with symptoms but do not remove the underlying disease. Donepezil (Aricept) and memantine (Namenda) are prescription medicines aimed at symptoms such as memory loss, confusion and trouble with everyday tasks. They are not designed to remove the underlying disease.

That distinction matters for expectations. A reasonable goal is a period of somewhat better or more stable function, not a return to how things were before.

How donepezil works

Donepezil belongs to a group called cholinesterase inhibitors. In Alzheimer's, levels of acetylcholine, a chemical messenger involved in memory and thinking, appear to fall. Donepezil slows the breakdown of acetylcholine, which may help nerve cells communicate a little better. The full picture of why it helps some people is not completely understood, and several factors probably contribute.

It is generally prescribed once a day. Clinicians often start with a low dose and adjust over time, so changes to the dose or the time of day should be made only by the prescriber.

How memantine works

Memantine works differently. It blocks NMDA-type glutamate receptors in the brain. Researchers think excess glutamate activity may harm nerve cells in Alzheimer's, though the exact way memantine helps is not fully understood. It is commonly used in moderate to severe disease, either alone or added to a cholinesterase inhibitor such as donepezil. Combining the two is common practice, and some people do better on the combination than on either drug alone, although results vary.

What "helping" realistically looks like

Clinical trials of both drugs have generally reported small average benefits on tests of thinking and on daily activities, and a prescriber can explain how those results apply to one person. Some families notice that a person seems a bit more alert, takes part in conversation a bit more, or manages dressing and eating a little longer. Others notice little change. Because the disease keeps progressing, a medicine that is working may show up as slower decline rather than visible improvement.

It can help to write down a few specific things before starting, such as how the person handles medications, meals, bathing or conversation. Comparing notes with the prescriber after a few months can give a clearer picture than memory alone.

Common side effects of donepezil

• Digestive upset: nausea, vomiting, diarrhea and reduced appetite can occur, especially early on or after a dose increase.
• Weight loss: can happen, and appetite and weight are worth tracking.
• Sleep changes and vivid dreams: may occur, and some clinicians discuss the timing of the dose with the family.
• Muscle cramps and fatigue: reported in some people.
• Slow heart rate: donepezil can slow the heartbeat, which may cause dizziness, falls or fainting in some people.

Product labeling for cholinesterase inhibitors such as donepezil describes a possible increased risk of stomach ulcers and bleeding, particularly with NSAIDs such as ibuprofen or aspirin. Seizures, trouble passing urine, and breathing problems in people with asthma or lung disease have also been described. Tell the prescriber about heart rhythm problems, ulcers, asthma or lung disease, seizures and difficulty passing urine so they can decide whether it is appropriate. Tell any surgeon, dentist or anesthesia team that the person takes donepezil, since it can interact with some anesthesia medicines. A severe allergic reaction, though uncommon, is an emergency. The urinary incontinence page is relevant too, since bladder symptoms can be part of aging and dementia and are worth raising with a clinician.

Common side effects of memantine

• Dizziness and headache: among the more frequently reported effects.
• Confusion or drowsiness: can occur, which is hard to sort out in someone who is already confused.
• Constipation: may occur and is worth reporting.
• Raised blood pressure: has been reported in some people.

Kidney function can affect how the body clears memantine, and product labeling calls for dose adjustment in severe kidney impairment, so the prescriber should know about any kidney disease. Some medicines that make the urine less acidic can also raise memantine levels, which is another reason to share the full medicine list. Memantine has also been associated with seizures in some people. Tell the prescriber about any history of seizures, since both memantine and donepezil may need extra caution in people prone to them.

Falls are a concern with any medicine that causes dizziness or a slow heart rate in an older adult. A fall with a head strike, especially in someone taking a blood thinner, can cause bleeding in the brain even when the person seems fine at first, and a fall with a suspected fracture or inability to stand also needs emergency evaluation.

Safety points for older adults

Older adults often take several medicines, and each added drug can raise the chance of interactions or side effects. Our article on polypharmacy in older adults, listed under Related Articles, covers that broader issue. Some medicines for bladder control, allergies, sleep or depression have anticholinergic effects, which work against donepezil and may worsen confusion. Medicines that slow the heart rate, such as beta-blockers or digoxin, may add to the risk of a slow pulse and fainting with donepezil. Tell the prescriber and pharmacist about all medicines, including over-the-counter sleep aids, bladder medicines, NSAIDs and supplements, before starting or changing either drug.

Do not stop, skip or change doses of either medicine on your own. Stopping donepezil suddenly may be followed by a drop in thinking or function in some people, so any change is best planned with the prescriber. Keep up any monitoring the prescriber recommends, such as pulse checks or weight tracking. People with heart rhythm problems, a history of seizures, ulcers or severe kidney disease need particular prescriber oversight with these medicines.

Checking whether it is working

Clinicians combine conversation with the person and family, examination and, often, brief memory screening. Ask about specific tasks rather than general impressions. If side effects outweigh benefits, the prescriber may adjust the plan, change drugs or discuss stopping. Practical help also matters: routines, safe driving decisions (see MedlinePlus on impaired driving), and caregiver support through MedlinePlus caregiver resources.

When symptoms may not be Alzheimer's

Memory trouble has many causes, including medication effects, infections, thyroid problems, vitamin deficiencies, depression and other forms of dementia. Dementia with Lewy bodies, for example, can respond differently to medicines and is covered in our Lewy body dementia comparison. Evening worsening of confusion is discussed in our article on sundowning. A change that comes on suddenly in someone with dementia can signal an acute problem such as infection or a medication reaction rather than ordinary progression, and should be evaluated promptly.

Questions to bring to the prescriber

• What changes should we watch for, and when should we report them?
• Could any current medicines or supplements interfere with these drugs?
• How will we decide together whether to continue?
• Is there a heart, lung, stomach or kidney condition that affects the choice?

When to Seek Medical Care