Does memantine cause sedation in an elderly patient with moderate‑to‑severe Alzheimer disease who is taking high‑dose donepezil (23 mg nightly) and possibly other cholinesterase inhibitors?

Is Memantine Sedating?

No, memantine is not sedating—in fact, it improves sleep architecture and reduces sleep fragmentation in geriatric patients with dementia, unlike cholinesterase inhibitors which commonly cause insomnia. 1

Sleep and Alertness Profile

• Memantine actually enhances sleep quality rather than causing sedation, demonstrating improvements in sleep architecture and reduced sleep fragmentation in elderly patients with dementia 1

• The most common neurological adverse effects of memantine are dizziness (6.1%), headache (5.5%), and confusion—not sedation or drowsiness 2, 3, 4

• While drowsiness is occasionally listed among possible adverse effects, it occurs rarely and is mild and transient when present 2, 5

Contrast with Cholinesterase Inhibitors

This is particularly relevant for your patient on high-dose donepezil (23 mg nightly):

• Cholinesterase inhibitors like donepezil cause insomnia as a significant adverse effect, especially in patients with cognitive impairment 1

• Adding memantine to donepezil therapy does not increase sedation risk—the combination is well-tolerated with no significant increase in serious adverse events 6

• Memantine may actually provide a protective effect against agitation (RR 0.81,95% CI 0.66 to 0.99), with 25 fewer people per 1000 experiencing agitation compared to placebo 1, 4

Safety Profile in Your Clinical Scenario

For an elderly patient with moderate-to-severe Alzheimer's disease already taking high-dose donepezil:

• Withdrawal rates due to adverse effects are comparable to placebo (9-12% for memantine versus 7-13% for placebo) 7, 4

• The combination of memantine plus donepezil is well-tolerated both as monotherapy and in combination, with memantine demonstrating benefits in neuropsychiatric symptoms and reduced caregiver distress 6, 4

• Common adverse effects are gastrointestinal (constipation, diarrhea, nausea), dizziness, and headache—not sedation 2, 3, 4

Clinical Bottom Line

Memantine should not be avoided due to sedation concerns in your elderly patient on high-dose donepezil. If anything, memantine may improve sleep quality while providing additional cognitive and behavioral benefits without adding sedative effects 1, 6. The primary adverse effects to monitor are dizziness, headache, and gastrointestinal symptoms, not sedation 3, 4.