Aricept and Namenda are both FDA-approved medications for Alzheimer’s disease, but they work through entirely different mechanisms and are approved for different stages of the illness. Aricept (donepezil) is a cholinesterase inhibitor that prevents the breakdown of acetylcholine, a neurotransmitter essential for memory and learning. Namenda (memantine) is an NMDA receptor antagonist that blocks excess glutamate activity, which can become toxic to nerve cells when levels run too high.
In short: they target different chemical problems in the brain, which is why doctors sometimes prescribe both at the same time. A useful way to think about it — Aricept tries to preserve the brain’s existing communication signals, while Namenda tries to protect nerve cells from being overwhelmed by overstimulation. A person diagnosed with moderate Alzheimer’s might be started on Aricept first, then have Namenda added later as the disease progresses. This article covers how each drug works, which stages they are approved for, what side effects to expect, and what the evidence says about using them together.
Table of Contents
- How Do Aricept and Namenda Work Differently in the Brain?
- Which Stages of Alzheimer’s Is Each Drug Approved For?
- Side Effects — What Families Should Know About Each Medication
- Can Aricept and Namenda Be Taken Together?
- Cost, Generics, and Insurance Considerations
- How These Medications Fit Into the Broader Alzheimer’s Treatment Landscape
- What to Discuss With the Neurologist or Geriatrician
- Conclusion
- Frequently Asked Questions
How Do Aricept and Namenda Work Differently in the Brain?
Aricept belongs to a class of drugs called cholinesterase inhibitors. In Alzheimer’s disease, levels of acetylcholine — a chemical messenger involved in attention, memory, and learning — drop significantly as neurons die. Aricept works by blocking the enzyme that breaks down acetylcholine, leaving more of it available in the brain’s synapses. It does not stop the underlying disease process, but it can help maintain cognitive function for a period of time by compensating for that chemical deficit. Namenda operates on an entirely different pathway.
It targets NMDA receptors, which respond to glutamate, the brain’s primary excitatory neurotransmitter. In Alzheimer’s, glutamate activity can become dysregulated, flooding receptors in a way that overstimulates and eventually damages nerve cells — a process called excitotoxicity. memantine partially blocks these receptors, reducing that toxic overactivation while still allowing normal signaling to occur. Think of it as turning down the volume on a signal that has become destructive rather than helpful. Because the two drugs act on completely separate neurochemical systems, they do not compete with each other or cancel each other out. This is the scientific rationale behind using them in combination, which is an approach supported by current clinical practice and increasingly by research data.
Which Stages of Alzheimer’s Is Each Drug Approved For?
One of the most clinically important distinctions between Aricept and Namenda is their approved indications. Aricept is FDA-approved for all three stages of Alzheimer’s disease — mild, moderate, and severe. It is often the first medication prescribed after a diagnosis, even in early stages when symptoms are still relatively manageable. Namenda, by contrast, is only FDA-approved for moderate-to-severe Alzheimer’s. It is not indicated for mild-stage disease. This distinction matters practically.
If a person receives a diagnosis of mild Alzheimer’s, their neurologist may prescribe Aricept but would not prescribe Namenda at that point — at least not within its approved indication. The staging guidelines reflect the clinical trial data submitted for FDA approval, meaning Namenda has not been shown to provide significant benefit in mild Alzheimer’s in the studies required for that approval. Some physicians do prescribe medications off-label, but the evidence base for Namenda in mild disease is weaker than for Aricept. A word of caution: staging in Alzheimer’s is not always precise or universally agreed upon. “Moderate” can mean different things depending on whether a clinician is using the Clinical Dementia Rating scale, the MMSE score, or their own clinical judgment. When a family member asks why their relative is or is not on one of these medications, the answer often comes down to how the physician has categorized the current stage of disease — and that conversation is worth having directly with the prescribing doctor.
Side Effects — What Families Should Know About Each Medication
Aricept and Namenda have different side effect profiles, which is useful information when a patient starts experiencing new symptoms after a medication change. Aricept’s most common side effects include nausea, diarrhea, headache, and muscle cramps. These tend to be most pronounced when the medication is first started or when the dose is increased, and many patients find they diminish over the first few weeks. Taking Aricept at bedtime, as is typically recommended, can help blunt some of these gastrointestinal effects. Namenda’s common side effects include dizziness, headache, confusion, and constipation. The confusion side effect deserves special attention in an Alzheimer’s context — it can be difficult to distinguish medication-induced confusion from disease progression.
If a person with Alzheimer’s seems notably more disoriented shortly after starting or increasing Namenda, that timing is worth flagging to their physician. It does not necessarily mean the drug is wrong for them, but the dose may need adjustment. One real-world example that comes up with some regularity: a family notices their loved one is sleeping more heavily and having vivid dreams after starting Aricept. This is a known, if less commonly discussed, effect — donepezil can affect REM sleep. Switching to a morning dose sometimes helps, though the standard recommendation is evening dosing. Any such change should be discussed with the prescribing physician rather than adjusted unilaterally.
Can Aricept and Namenda Be Taken Together?
Yes — and this combination is both FDA-approved and increasingly common in clinical practice. Because Aricept and Namenda work on different neurotransmitter systems, there is no pharmacological conflict in using them simultaneously. The FDA has recognized this by approving Namzaric, a combination pill that contains both memantine and donepezil in a single extended-release capsule. Namzaric is approved specifically for moderate-to-severe Alzheimer’s in patients already stabilized on the individual drugs. The rationale for combination therapy is that targeting two different pathways simultaneously may provide greater benefit than either drug alone.
A 2024 study published in Communications Medicine (a Nature journal) found that combined use of the two medications was associated with an increased probability of 5-year survival in Alzheimer’s patients compared to monotherapy or no treatment. A prior meta-analysis in PMC also examined the combination and found meaningful clinical signals, though the research landscape is complex and not every study shows the same magnitude of benefit. The practical tradeoff worth discussing with families: adding Namenda to an existing Aricept regimen means another medication to manage, another set of potential side effects to monitor, and — depending on insurance and coverage — potentially another cost. However, both drugs are now available as generics (generic donepezil and generic memantine), which has significantly reduced out-of-pocket costs compared to when only the brand-name versions were available. The combination pill Namzaric may or may not be more cost-effective than taking the generics separately, so it is worth checking with a pharmacist.
Cost, Generics, and Insurance Considerations
Cost was a significant barrier to these medications when they were available only as brand-name drugs. Aricept’s patent has long since expired, and generic donepezil is now widely available and typically inexpensive — often covered with minimal copays under most Medicare Part D and commercial insurance plans. The same applies to generic memantine, the generic form of Namenda. For many patients, the monthly out-of-pocket cost for both generics together is quite manageable compared to the brand-name era. Namzaric, the combination pill, remains a branded medication and is considerably more expensive than taking generic donepezil and generic memantine separately.
If a physician recommends Namzaric for convenience — one pill instead of two — it is entirely reasonable to ask whether taking the two generics separately achieves the same therapeutic result. In most cases, it does. The combination pill offers no pharmacological advantage over the separate generics; it is primarily a convenience formulation. One important warning: some insurance formularies cover one extended-release formulation of memantine but not another, or may require prior authorization for Namzaric. It is worth verifying coverage before a prescription is filled, particularly for patients on fixed incomes. Patient assistance programs exist for some of these medications, and a social worker at a memory care center or a pharmacist can help navigate those options.
How These Medications Fit Into the Broader Alzheimer’s Treatment Landscape
Aricept and Namenda have been the backbone of Alzheimer’s pharmacotherapy for decades, but it is worth placing them in context. Neither drug slows or halts the underlying progression of Alzheimer’s disease — they manage symptoms and may help maintain function longer, but the disease continues to advance. Newer treatments, including anti-amyloid antibodies like lecanemab (Leqembi), represent a different category: disease-modifying therapies that target amyloid plaques in the brain.
These newer drugs are not replacements for Aricept or Namenda; they address a different aspect of the disease biology and are typically used in earlier stages. For the majority of people living with moderate-to-severe Alzheimer’s today, donepezil and memantine remain the standard pharmacological tools — affordable, relatively well-tolerated, and supported by decades of real-world use. The goal of treatment is to preserve quality of life and functional independence for as long as possible, and these medications, when appropriate, contribute to that goal.
What to Discuss With the Neurologist or Geriatrician
The decision to start, continue, or discontinue either of these medications should always be made in partnership with a physician who knows the patient’s full clinical picture. Relevant questions to bring to that conversation include: What stage is this disease currently at, and does that affect which medications are appropriate? If one drug has been tried and caused intolerable side effects, is there a reason to try adjusting the dose rather than stopping entirely? Is the combination appropriate given where the disease is now? And — importantly — what are the realistic expectations? These medications are not a cure, and honest conversations about what they can and cannot do are essential for families navigating long-term care decisions.
The research landscape continues to evolve. The 2024 Nature Communications Medicine findings on 5-year survival add to a growing body of evidence suggesting that combination therapy has real, measurable benefits. As the field of Alzheimer’s pharmacology advances, the role of donepezil and memantine may evolve — but for now, they remain central to standard care.
Conclusion
Aricept and Namenda are not interchangeable drugs — they work through different mechanisms, are approved for different stages of Alzheimer’s, and have different side effect profiles. Aricept targets the cholinergic system by preserving acetylcholine levels and is approved across all stages of Alzheimer’s. Namenda targets the glutamate system through NMDA receptor blockade and is approved only for moderate-to-severe disease.
When prescribed together, they address two distinct neurochemical problems simultaneously, and both are now available as affordable generics. For families supporting someone with Alzheimer’s, understanding these differences helps you ask better questions and participate more fully in treatment decisions. If a loved one is on one of these medications but not the other, it does not necessarily mean something is being missed — it may simply reflect the current stage of the disease or a clinical judgment call. What matters most is ongoing communication with the prescribing physician, attention to side effects, and realistic expectations about what these medications can and cannot do.
Frequently Asked Questions
Can Aricept be taken for mild cognitive impairment (MCI), not just Alzheimer’s?
Aricept is FDA-approved specifically for Alzheimer’s disease, not for mild cognitive impairment. Some physicians prescribe it off-label for MCI, but the evidence for benefit in that population is limited and it is not standard practice.
What is Namzaric and how is it different from taking Namenda and Aricept separately?
Namzaric is an FDA-approved combination pill containing memantine and donepezil in one extended-release capsule. It offers no pharmacological advantage over taking the two generic drugs separately — the primary benefit is convenience. It is typically more expensive than taking generic donepezil and generic memantine individually.
Does Namenda work for all types of dementia, or just Alzheimer’s?
Namenda (memantine) is FDA-approved specifically for moderate-to-severe Alzheimer’s disease. It is sometimes used off-label for other dementias, including vascular dementia, but the evidence base is strongest for Alzheimer’s.
When should someone stop taking these medications?
This is a question for the treating physician. In advanced-stage Alzheimer’s, some clinicians deprescribe these medications if the patient can no longer swallow pills safely, if benefits appear minimal, or as part of a comfort-focused care transition. There is no universal standard, and the decision should reflect the patient’s goals of care.
How long does it take to see effects from Aricept or Namenda?
Effects can be subtle and are not always immediately obvious to families. In clinical trials, meaningful differences on cognitive assessments were seen over months, not days. These medications are generally evaluated over a period of three to six months to assess benefit, though individual responses vary considerably.
Are there people who should not take these medications?
Yes. Aricept should be used with caution in people with certain heart rhythm abnormalities (it can slow heart rate), active peptic ulcers, or asthma. Memantine requires dose adjustment in people with severe kidney impairment. A full medication review with the prescribing physician and pharmacist is important before starting either drug.
