Can memantine cause hypertension in older adults treated for moderate‑to‑severe Alzheimer disease?

Can Memantine Cause Hypertension?

Hypertension is not a recognized adverse effect of memantine at therapeutic doses in older adults with moderate-to-severe Alzheimer's disease, but has been documented in cases of memantine overdose. 1

Evidence from Clinical Trials

The extensive clinical trial data for memantine does not identify hypertension as a common or significant adverse effect at standard therapeutic doses:

• Withdrawal rates due to adverse effects are comparable between memantine (9-12%) and placebo (7-13%) groups, with no specific mention of hypertension as a contributing factor 2, 3

• The most commonly reported adverse effects in clinical trials include:

  • Gastrointestinal symptoms (nausea, diarrhea): 4-18% 4
  • Dizziness: 6.1% versus 3.9% with placebo 5
  • Headache: 5.5% versus 4.3% with placebo 5
  • Agitation: 4-18%, though memantine actually shows a protective effect against agitation compared to placebo 2, 4

• High-certainty evidence from multiple trials shows no difference in the overall proportion of patients experiencing at least one adverse event between memantine and placebo (RR 1.03,95% CI 1.00 to 1.06) 5

Hypertension in Overdose Situations

Hypertension has been documented as a feature of memantine overdose, which is an important clinical consideration:

• A 2024 case report describes an 86-year-old man with mild dementia and pre-existing hypertension who developed hypertensive urgency requiring nicardipine infusion after ingesting approximately 60 memantine tablets 1

• This case highlights that hypertension from memantine overdose can be easily misattributed to medication non-compliance in patients with pre-existing hypertension, emphasizing the importance of early medication reconciliation with caregivers 1

• The hypertensive effects resolved within 100 hours, consistent with memantine's half-life, supporting a causal relationship in overdose scenarios 1

Clinical Implications

In routine clinical practice at therapeutic doses (20 mg/day or 28 mg extended release), hypertension should not be expected as an adverse effect of memantine. 2, 3, 5

Important Caveats:

• If hypertension develops in a patient taking memantine, consider:

  • Progression of underlying vascular disease
  • Non-adherence to antihypertensive medications (particularly relevant in dementia patients)
  • Drug interactions with other medications
  • Accidental overdose (verify pill counts with caregivers) 1

• The case example from the American Geriatrics Society guidelines illustrates potential drug interactions: a patient on both metoprolol and donepezil experienced bradycardia (both agents can slow heart rate), demonstrating how medication effects can be multifactorial in older adults with polypharmacy 2

Memantine is well-tolerated both as monotherapy and in combination with cholinesterase inhibitors, with no significant increase in serious adverse events. 3, 6