Should memantine be discontinued because of new onset nausea, vomiting, diarrhea, and dizziness?

Memantine Should Be Discontinued If These Side Effects Are Intolerable

Discontinue memantine gradually if the patient is experiencing intolerable nausea, vomiting, diarrhea, and dizziness, as these symptoms meet criteria for deprescribing based on development of intolerable side effects. 1

Clinical Decision Framework

The 2020 Canadian Consensus Conference on Dementia provides explicit guidance that memantine discontinuation should be considered when there is "development of intolerable side effects (eg, confusion, dizziness, falls)" 1. While the guideline specifically lists confusion, dizziness, and falls as examples for memantine, it separately lists "severe nausea, vomiting" as intolerable side effects warranting discontinuation of cholinesterase inhibitors 1.

The key determination is whether these symptoms are "intolerable" - meaning they significantly impact the patient's quality of life or safety. The presence of multiple gastrointestinal symptoms (nausea, vomiting, diarrhea) combined with dizziness suggests a substantial adverse effect burden.

Evidence on Memantine Side Effects

The FDA label confirms that dizziness is among the most common adverse reactions (incidence ≥5% and higher than placebo) in memantine-treated patients 2. The label also documents that vomiting and dizziness are recognized overdosage symptoms 2. Research data shows these adverse events occur but are generally mild and transient 3, 4.

However, nausea, diarrhea, and vomiting are more characteristic of cholinesterase inhibitors rather than memantine 3. This raises an important clinical consideration: if the patient is on combination therapy with a cholinesterase inhibitor, those gastrointestinal symptoms may actually be attributable to the cholinesterase inhibitor, not memantine. The dizziness could be from memantine.

Deprescribing Protocol

If discontinuation is warranted, follow the gradual tapering protocol 1:

• Reduce dose by 50% every 4 weeks until reaching the initial starting dose
• After 4 weeks at the starting dose, discontinue completely
• Monitor for clinically meaningful worsening of cognition, function, neuropsychiatric symptoms, or global assessment
• Reinitiate treatment if significant decline occurs that appears related to cessation 1

Critical Caveats

Before discontinuing, verify:

1. Attribution: Are these symptoms actually from memantine or from a concomitant cholinesterase inhibitor? Gastrointestinal symptoms are far more common with cholinesterase inhibitors 3

2. Timing: Are these new symptoms or pre-existing? The question states "recently now has" these symptoms, suggesting new onset

3. Severity: Distinguish between mild transient effects versus truly intolerable symptoms affecting quality of life

4. Alternative causes: Rule out other medical conditions, drug interactions, or delirium that could explain these symptoms

5. Treatment duration: The guideline specifically addresses patients on memantine for >12 months 1, though intolerable side effects warrant consideration regardless of duration

If the patient is on combination therapy (memantine + cholinesterase inhibitor), consider discontinuing or reducing the cholinesterase inhibitor first, as it is the more likely culprit for the gastrointestinal symptoms 3, 5.