Memantine Versus Donepezil – Understanding the Nuances

In the realm of Alzheimer’s disease treatment, two medications often stand out: memantine (Namenda) and donepezil (Aricept). These drugs are frequently prescribed to manage symptoms and improve the quality of life for individuals grappling with Alzheimer’s dementia. However, understanding the nuances and differences between them is crucial for patients and providers. In this article, we will compare some of the differences between memantine versus donepezil.


Memantine is an NMDA receptor antagonist, which means it works by regulating the activity of glutamate, a neurotransmitter involved in learning and memory. It is FDA-approved for moderate to severe Alzheimer’s disease. Namenda is believed to protect brain cells from excess glutamate, thereby slowing down cognitive decline. Its main benefits include the slowing of the disease progression and Improved cognitive functioning while being well-tolerated and only having a few side effects like headache, constipation, CNS changes, and dizziness as compared to other agents.


Donepezil belongs to a class of drugs called acetylcholinesterase inhibitors. It works by increasing the levels of acetylcholine, a neurotransmitter involved in memory and learning. Donepezil is FDA-approved for mild to moderate Alzheimer’s disease at 10 mg and moderate to severe at the 23 mg dose. Its main benefits include symptom Improvement especially when it comes to cognitive functioning, memory, and behavior in individuals with Alzheimer’s disease. As with most medications, side effects tend to be dose-dependent and are more likely to occur at higher dosages. Side effects include nausea, diarrhea, weight loss, insomnia, urinary frequency, and bradycardia (think the opposite of anticholinergic medications). 

Memantine Versus Donepezil Elimination

Namenda’s elimination is partially dependent on renal function, so dosage adjustments are recommended for patients with impaired kidney function to prevent potential adverse effects. Donepezil’s metabolism on the other hand doesn’t heavily rely on renal function, so dosage adjustments are less necessary in patients with impaired kidney function compared to Namenda.

While both Namenda and Donepezil are used to treat Alzheimer’s disease, they work through different mechanisms and are often prescribed together to maximize therapeutic effects. Namenda targets glutamate regulation, while Donepezil focuses on enhancing acetylcholine levels. In some cases, healthcare providers may prescribe Namenda and Donepezil together to target multiple pathways involved in Alzheimer’s disease progression. This combination therapy has been shown to provide greater benefits regarding symptom management and disease progression compared to either medication alone.

Other Indications

When comparing memantine versus donepezil, it is important to look at other indications. In addition to their use in Alzheimer’s disease, Donepezil may be preferred in Parkinson’s disease dementia due to its effectiveness in managing cognitive symptoms associated with this condition. Parkinson’s disease dementia often presents with similar cognitive symptoms as Alzheimer’s disease, and Donepezil has shown efficacy in improving cognitive function in this population. Memantine additionally has some evidence for two unique indications; prevention of neurocognitive toxicity with brain irradiation and uniquely, trichotillomania (hair pulling) and skin picking (excoriation) disorder. 

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This article was written by Jack Mageto, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP


  • Alzheimer’s Association . (2019). Alzheimer’s disease facts and figures. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association., 15(3), 321–387. 
  • Namenda, IBM Micromedex® DrugPoint Summary (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: (accessed: March 8, 2024).
  • Donepezil, IBM Micromedex® DrugPoint Summary (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: (accessed: March 8, 2024).
  • Allergan. Namenda Product Information.
  • Eisai R&D Management Co., Ltd. Aricept Product Information.
  • Ravina B, Putt M, Siderowf A, Farrar JT, Gillespie M, Crawley A, Fernandez HH, Trieschmann MM, Reichwein S, Simuni T. Donepezil for dementia in Parkinson’s disease: a randomised, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry. 2005 Jul;76(7):934-9. doi: 10.1136/jnnp.2004.050682. PMID: 15965198; PMCID: PMC1739697.

1 Comment

  1. Alma

    Appreciate the information especially why providers combine therapy


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Written By Eric Christianson

March 20, 2024

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