An Emerging Off-Label Option: Is Memantine Used for Migraines?

October 9, 2025 •

4 min read

Affecting nearly 1 in 7 people globally, migraine is a leading cause of disability [1.9.5]. While not FDA-approved for this purpose, a growing body of evidence explores the question: is memantine used for migraines? This Alzheimer's medication is showing promise as an off-label preventive treatment [1.3.1, 1.3.2].

Quick Summary

Memantine, a drug for Alzheimer's, is increasingly prescribed off-label for migraine prevention. It works by targeting glutamate activity in the brain, which is implicated in migraine pathophysiology. Studies show it can significantly reduce migraine frequency and severity.

Key Points

Off-Label Use: Memantine is approved for Alzheimer's but is used off-label for migraine prevention due to its mechanism of action [1.3.2].
Glutamate Modulation: It works by blocking NMDA receptors, reducing the excessive glutamate activity implicated in migraine attacks [1.4.2].
Clinical Efficacy: Randomized controlled trials show memantine significantly reduces monthly migraine frequency compared to placebo [1.2.2, 1.2.5].
Good Tolerability: Memantine is generally well-tolerated, with mild side effects like dizziness and confusion that are often comparable to placebo [1.2.5, 1.3.6].
Favorable for Some Patients: It may be a valuable option for patients with refractory migraines or those who cannot tolerate standard preventive medications [1.3.4].
Dosage: Treatment typically involves a slow titration from 5 mg up to 10-20 mg per day to minimize side effects [1.2.2, 1.4.1].
Pregnancy Safety Profile: It is a Pregnancy Category B drug, which may give it an advantage over some other preventives like Topiramate (Category D) [1.8.1, 1.2.2].

From Alzheimer's to Aura: Understanding Memantine

Memantine, sold under brand names like Namenda, is a medication primarily approved by the U.S. Food and Drug Administration (FDA) for treating moderate to severe dementia associated with Alzheimer's disease [1.4.5, 1.3.1]. Its journey into the realm of headache medicine is a compelling example of how understanding a drug's mechanism of action can reveal new therapeutic possibilities. While its application for migraines is considered off-label, meaning it's not officially approved for this use, a growing number of neurologists are prescribing it for patients with frequent or difficult-to-treat migraines, particularly refractory cases where other standard therapies have failed [1.3.2, 1.3.4].

The Glutamate Connection: How Memantine May Prevent Migraines

The scientific rationale for using memantine for migraines lies in its unique effect on the brain's glutamatergic system [1.4.3]. Glutamate is the most abundant excitatory neurotransmitter in the brain, and excessive glutamate activity is believed to play a key role in migraine pathophysiology [1.4.1, 1.7.3].

Specifically, overstimulation of a type of glutamate receptor called the N-methyl-D-aspartate (NMDA) receptor is thought to facilitate a phenomenon known as Cortical Spreading Depression (CSD) [1.4.2]. CSD is a wave of intense nerve cell activity followed by a period of suppression, which is considered the underlying cause of migraine aura and a trigger for headache pain [1.4.1].

Memantine acts as a low-to-moderate affinity, uncompetitive antagonist of the NMDA receptor [1.4.4, 1.4.5]. This means it blocks the receptor channel, but only when it's excessively open, as it is under pathological conditions. This action inhibits the prolonged influx of calcium into neurons that leads to excitotoxicity (nerve cell damage from overstimulation) without disrupting the normal, healthy synaptic activity necessary for learning and memory [1.2.1, 1.4.2]. By modulating this hyperactivity, memantine may raise the threshold for initiating CSD, thereby preventing migraine attacks before they start [1.4.2].

Evidence from Clinical Studies

Multiple studies have investigated memantine's effectiveness for migraine prophylaxis, with generally positive results:

A 2015 randomized, double-blind, placebo-controlled trial found that patients taking 10 mg/day of memantine had a significantly greater reduction in monthly migraine attacks compared to placebo (a mean change of 3.4 attacks vs. 1.0) [1.2.2].
Another randomized controlled study published in 2019 showed that over 24 weeks, memantine (10 mg/day) reduced migraine frequency to 2.57 attacks per month from a baseline of 10.79, compared to a reduction to 5.07 attacks in the placebo group. The 50% responder rate was 85.7% for memantine versus 51.7% for placebo [1.2.5].
An open-label study on patients with refractory migraines demonstrated that memantine reduced the frequency of migraines by nearly 58% (from 9.6 to 4.1 per month) [1.2.1].
More recent research, including a 2025 study on adolescents and a 2024 network meta-analysis, continues to support its potential efficacy and safety, suggesting it can significantly decrease headache days and is well-tolerated [1.2.3, 1.2.6].

Dosing and Side Effects

In clinical studies for migraine, memantine is typically started at a low dose of 5 mg per day and gradually titrated up to a target dose of 10 mg or 20 mg per day [1.2.2, 1.4.1]. This slow titration helps minimize potential side effects [1.6.2].

The side effect profile of memantine is generally considered mild and well-tolerated, especially when compared to other oral migraine preventives [1.2.1, 1.3.6]. The most commonly reported side effects include:

Dizziness [1.6.1, 1.6.3]
Headache [1.6.1]
Confusion [1.6.1]
Constipation [1.6.2]
Drowsiness or fatigue [1.2.2, 1.2.3]

In various placebo-controlled trials, the incidence of these side effects in the memantine group was often similar to that of the placebo group [1.2.5].

Comparison with Other Migraine Preventives

To understand memantine's place in treatment, it's useful to compare it to an established option like topiramate.


Feature	Memantine (Off-Label)	Topiramate (FDA-Approved)
Mechanism	NMDA receptor antagonist; modulates glutamate activity [1.4.2].	Multiple mechanisms, including blocking sodium channels and enhancing GABA activity [1.8.1].
Common Side Effects	Dizziness, confusion, headache, constipation [1.6.3].	Tingling, memory loss, weight loss, 'brain fog' [1.8.1].
Pregnancy Category	Category B (No proven risk in human studies) [1.8.1].	Category D (Positive evidence of risk) [1.8.1].
Titration	Typically requires a short titration period [1.2.2].	Often requires a longer, slower titration to manage side effects.
Efficacy	Studies show significant reduction in migraine days vs. placebo [1.2.2, 1.2.5]. A meta-analysis found it had high response rates compared to other drugs [1.2.6].	Established efficacy for migraine prevention.
Insurance Coverage	Often not covered for migraine as it's off-label [1.8.4].	Generally covered for its approved indication of migraine prevention.

Conclusion: A Promising but Off-Label Tool

So, is memantine used for migraines? The answer is yes, as an off-label preventive option with a strong scientific basis and encouraging clinical evidence. Its unique mechanism of action targeting the glutamate system, favorable side effect profile, and good tolerability make it an attractive alternative, particularly for patients who have not found success with or cannot tolerate standard therapies [1.3.4, 1.2.2]. While larger, long-term studies are still needed to firmly establish its place in migraine treatment guidelines, memantine represents a valuable and promising tool in the expanding arsenal against this debilitating neurological disorder. Patients interested in this option should discuss it with their neurologist to determine if it is an appropriate choice for their specific situation.

For further reading, a comprehensive review on the role of memantine in adult migraine can be found in the National Library of Medicine: Role of memantine in adult migraine: a systematic review and network meta-analysis [1.2.6]

Frequently Asked Questions

No, memantine is not FDA-approved for the treatment or prevention of migraines. Its use for this purpose is considered off-label, based on its mechanism and emerging clinical evidence [1.3.1, 1.3.2].

Memantine works by blocking NMDA-type glutamate receptors. This action helps to prevent excessive neuronal excitation in the brain, a process known as excitotoxicity, which is believed to be a key factor in triggering migraine attacks [1.4.2, 1.4.4].

In clinical studies, the effective dose of memantine for migraine prevention is typically 10 mg to 20 mg per day. Treatment usually starts at a lower dose and is increased gradually [1.2.2, 1.4.1].

The most common side effects are generally mild and include dizziness, headache, confusion, and constipation. Many studies report its side effect profile as very tolerable [1.6.1, 1.3.6].

Several randomized controlled trials have shown that memantine can significantly reduce the frequency and severity of migraine attacks compared to a placebo. One study noted an 85.7% responder rate (at least 50% reduction in frequency) in the memantine group [1.2.2, 1.2.5].

Yes, memantine has been studied and used in patients with both episodic and chronic migraine, often showing effectiveness in reducing headache frequency even in refractory cases where other treatments have failed [1.2.3, 1.3.4].

Memantine often has a more favorable side effect profile, with less risk of cognitive issues like 'brain fog' associated with topiramate. It also has a better pregnancy safety rating (Category B vs. Category D for topiramate) [1.8.1, 1.2.2].