In this blog, I am going to describe why and how two common medications are commonly prescribed for people living with dementia: acetylcholine esterase inhibitors (pronounced a-SEE-tol-CO-leen ES-ter-ace) and memantine (prounounced meh-MAN-teen). In these next couple of blogs, I’m going to describe other common medications that persons living with dementia may be prescribed.
Donepezil (Aricept)
Donepezil (pronounced doh-NEP-eh-zil)–which is the generic name for Aricept– is a acetylcholinesterase-inhibitor, meaning that it prevents the body from making the enzyme cholinesterase, which breaks down acetylcholine.
NOTE: You will see the terms “choline esterase” and “acetylcholine esterase” used interchangeably. Either are correct.
Acetylcholine is very important for the making and retaining of memories. In a brain without dementia, certain nerve cells constantly make chemicals like acetylcholine. Then other neurons secrete enzymes that break down acetylcholine, suck up the raw materials, and make new acetylcholine. This process results in a “fresh” supply of acetylcholine at all times. The brain cells function like an air purifier, continuously providing a ready batch of “fresh” neurochemicals.
In a brain with dementia, neurons are dying off. As the number of healthy neurons decreases, the level of fresh acetylcholine also drops—there are fewer healthy neurons to make acetylcholine. At the same time, the neurons who are supposed to be secreting enzymes to break down the acetylcholine are still doing their job. If I could stop neurons from breaking down the acetylcholine, I could–temporarily–keep the acetylcholine levels higher. Maybe even boost the levels for a little while.
Donepezil (and the other AChEIs) does exactly that. Donepezil manages to keep the level of good acetylcholine higher than the number of healthy cells available to make it. Donepezil does this by blocking the breakdown of acetylcholine. Donepezil blocks the breakdown by INHIBITING (blocking) specific neurons from squirting out the enzymes that break down acetylcholine. Yay! But..this is a temporary fix. Acetylcholine “goes bad,” meaning it “degrades” and falls apart over time. Even though the donepezil keeps the levels of acetylcholine a smidge higher than the level would be without the medication, the levels do still drop over time. At some point, the the level of acetylcholine drops to a new low. This is where you will see that the person living with dementia is having more memory problems and self-care problems.
Donepezil Usage and Side Effects
Donepezil is approved for mild, moderate, and severe Alzheimer’s dementia. It can be prescribed for people with vascular dementia. Previous research findings reported inconsistent results wehn given to people living with vascular dementia. Many people have both vascular dementia and AD; this may be why the donepezil worked better for some compared to others.
The usual dosage is 10 mg daily; however, it can be given as high as 23 mg daily. The issue with the higher dosages is that the side effects are dose-dependent, while efficacy is less so. This is why you will rarely see the 23 mg dosage. Donepezil can result in overall improvement of neuropsychiatric behaviors–like agitation, arguing, and care refusals–but the effect of donepezil on behaviors in persons 85 years of age or older is weaker. Donepezil is USUALLY not appropriate for persons with frontal-temporal dementia because these individuals have normal levels of acetylcholine. In these cases, donepezil can create an acetylcholine-driven delirium. However, this is where getting the correct diagnosis is important. There are some people with AD but who appear to act like they have FTD–this is called frontotemporal variant AD.
Common side effects are predomoninatly based in the gut: nausea, vomiting, diarrhea. Other side effects include bradycardia (slow pulse), dizziness, syncope (fainting), tremors (worse in person with Parkinson Disease Dementia—rivastigmine, another type of cholinesterase inhibitor, may be a better choice and is FDA-approved for use in people with Parkinson Disease Dementia), and muscle weakness. The side effects are the result of stimulation of cholinergic receptors in muscle, cardiac, and GI tissues.
Other AChEIs
As I mentioned earlier, other members of the acetylcholinesterase inhibitor family include rivastigmene (Exelon) and galantamine (Razadyne).
Rivastigmine
Like donepezil, rivastigmine (RIV-ah-STIG-meen) is used for people living with mild to moderate dementia. Rivastigmine is available in pill form, liquid form, and patch form. The dosage for pill and liquid forms range from 1.5 mg twice a day to 6 mg twice a day. Your health care provider will likely move up the dosage gradually–usually by 1.5 mg every 2 weeks. If your family member is taking the capsule, do not crush it. Ask your provider to prescribe the liquid form. The liquid form can be given straight or mixed with a small amout (2-3 ounces) of water, soda, or cold fruit juice. As I indicated earlier in this blog, it is the only medication in the AChEI class that is FDA-approved for Parkinson’s Disease dementia.
Galantamine (Razadyne)
This is another member of the AChEI family, and is available as a immediate-acting pill, extended release capsule, and liquid. The dosage is usually 8 mg daily for the extended-release capsules, which can be increased by 8 mg after 4 weeks. Maximum dosage is 24 mg daily, and this medication needs to be taken with food. The dosage is the same for the immediate-acting pill and liquid, but the medication is given twice a day. For example, people taking the immediate-acting pill or liquid would take 4 mg twice a day instead of one 8-mg capsule.
Drug Interactions
Sometimes, older adults are taking medications that cancel each other out while increasing side effects: like taking both a pro-cholinergic medication (donepezil) and an anticholinergic medication (oxybutynin). It is always a good idea to bring all of the medication bottles to each medical appointment (especially with specialists who tend to get tunnel-vision) and double-check that new medications won’t cause new problems.
When to stop Donepezil
Donepezil is prescribed to slow down the progression of dementia. Once a person with dementia requires full-time care, donepezil may no longer be needed. ONE NOTE OF CAUTION: if the individual with dementia is able to walk around independently or can feed him/herself, stopping the donepezil may result in the loss of these abilities. Donepezil at the 10 mg daily dose does not need to be tapered; it can be stopped immediately. Some clinicians think that a taper is needed because of the FDA’s recommendation that donepezil be started at 5 mg for 4-6 weeks before increasing to the daily 10 mg dosage. This recommendation was made because participants in the clinical studies who followed the slower route to the 10 mg dosage had much fewer side effects than the participants whose dosages were increased after a week on the medication. If there is concern about a decline in function or an increase in agitation, the donepezil can be dropped from 10 mg to 5 mg for a week. At the point, the person should be evaluated and if there are no new problems or behaviors, the medication can be stopped. On the other hand, if the decrease in dosage results in an increase in behaviors or a significant decline (for example, the individual was walking independently but the staff notice problems walking after the dosage was reduced), it may be prudent to return to the 10 mg dosage.
Memantine (Namenda)
Memantine (Namenda) is an N-methyl-D-aspartate (NMDA) receptor ANTAGONIST, meaning it blocks this receptor from being stimulated by other neurochemicals. Chronic activation of NMDA receptors over time contributes to shrinkage of the brain matter–a process known as “excitotoxicity.” This excitotoxic pathway is also thought to contribute to the changes in cognition and personality often seen in survivors of traumatic brain injury.
Memantine Usage and Side Effects
Memantine is approved for use in moderate to severe Alzheimer’s Disease only. When the cognitive test scores decline below the 66th percentile (for example, less than 20 for the MMSE), clinicians often introduce memantine. Published research is difficult to interpret because of the volumes of publications funded by the pharmaceutical industry. However, I located some solid meta-analyses and integrative reviews that suggest that memantine can help slow down the loss of cognition in persons who have vascular dementia. Memantine does not help with the dementia-related behaviors. Also, monotherapy (memantine alone) is better than placebo BUT, the findings are mixed when examining the effect of combining memantine with donepezil–even though it is done all of the time.
Side effects include constipation, dizziness, headache, hypertension, and somnolence.
Memantine is approved for use in moderate to severe Alzheimer’s Disease only. When the cognitive test scores decline below the 66th percentile (for example, less than 20 for the MMSE), clinicians often introduce memantine. Published research is difficult to interpret because of the volumes of publications funded by the pharmaceutical industry. However, I located some solid meta-analyses and integrative reviews that suggest that memantine can help slow down the loss of cognition in persons who have vascular dementia. Memantine does not help with the dementia-related behaviors. Also, monotherapy (memantine alone) is better than placebo BUT, the findings are mixed when examining the effect of combining memantine with donepezil–even though it is done all of the time.
When to stop Memantine
Like the situation with donepezil, when a person with dementia requires placement and is no longer walking ndependently or engaging in any self-care activities, memantine may no longer be needed. ONE NOTE OF CAUTION: if the individual with dementia is able to walk independently or can feed him/herself, stopping the memantine may result in the loss of these abilities. Memantine should be discontinued in the reverse order of how it was started. If a significant decline in ability is noted, the person should return to the previous dosage level of the medication. For example, if the individual began having trouble walking when the memantine dosage was dropped from 10 mg daily to 5 mg daily, the dosage should go back to 10 mg daily—not the original 10 mg twice daily!
Families may fail to see progress and may ask about whether their loved one should be taking donepezil, memantine, both, or either. This is a valid question and the IDEAL SITUATION is for the prescribing clinician to have a conversation family members about goals of care and the risk/benefits of continuing or stopping either medications.
Bottom Line
I offer this information as education and as a way for caregivers to ask questions and advocate for their loved ones living with dementia. I see too many examples of caregivers giving each other advice about medication on support groups and in Facebook groups–and that information is WRONG!!! If you have cared for one person living with dementia–you have cared for ONE person living with dementia. The support from online groups and in-person support groups is fantastic. I’m not knocking the support. I am, however, thoroughly disgusted with many Facebook groups where real harm is happening because of the moderators are either clueless, absent, or both.
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Categories: Alzheimer's Disease Caregiving Dementia FTD Lewy Body Dementia Vascular Dementia
Dr. Rita Jablonski
Rita Jablonski, PhD, CRNP, FAAN, FGSA is a nurse practitioner, researcher, tenured professor, and former family caregiver. Her research and practice involve all aspects of dementia management; she is best known for non-drug strategies to address dementia-related behaviors.
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