In today’s post, I am going to answer a question that I receive many times a week: When is it OK to stop two common medications, Aricept (donepezil) and Namenda (memantine) for people with Alzheimer’s Disease?
The short answer: these medications are designed to slow down the nerve damage from AD. Neither medication treats the disease, just the symptoms. These medications are meant to delay the need for 100% care. Once that happens–once the person is now 100% dependent on others for care–the medication(s) have done their job and can be potentially stopped. PLEASE CONSULT WITH YOUR PROVIDER BEFORE STOPPING THE MEDICATIONS YOURSELF!!
Donepezil (Aricept) is a cholinesterase-inhibitor, meaning that it prevents the body from making the enzyme cholinesterase, which breaks down acetylcholine. Acetylcholine is very important for the making and retaining of memories. In a brain without dementia, nerve cells constantly make chemicals like acetylcholine. The cells then secrete enzymes that break down acetylcholine, suck up the raw materials, and then make new acetylcholine. This process results in a “fresh” supply of acetylcholine at all times.
In a brain with dementia, neurons are dying off. As the number of healthy neurons decrease, the level of fresh acetylcholine also drops—because the cells still secrete enzymes to break down the acetylcholine but there are fewer healthy cells to replace the acetylcholine. Donepezil manages to keep the level of good acetylcholine higher than the number of healthy cells. Acetylcholine, however, does degrade over time. At some point, the donepezil no longer keeps the levels of acetylcholine high enough and the person with dementia shows more memory problems and more loss in abilities to care for him or herself.
Donepezil Usage and Side Effects
Donepezil is approved for mild, moderate, and severe Alzheimer’s Disease. 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, but not in persons 85 years of age or older. Donepezil is not appropriate for persons with frontal-temporal dementia because these individuals have normal levels of acetylcholine; donepezil can create an acetylcholine-driven delirium.
Common side effects are the usual ones: GI (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.
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) 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 available in two forms: a short-acting preparation and an extended-release preparation. Memantine 10 mg twice daily provides the same benefits as memantine 28 mg extended release. The extended-release formulation, however, usually has much higher co-pays and costs more than the 10 mg shorter-acting formulation. Memantine is usually initiated at 5 mg daily for 7 days, then 10 mg daily for 7 days, then 15 mg daily (10 mg in AM, 5 mg in PM), then 10 mg twice daily. The XR formulation is prescribed as 7 mg for a week, 14 mg for a week, 21 mg for a week, then 28 mg daily.
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.
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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.