By Marcello Cherchi, MD PhD
For patients
Memantine is a pill that is mostly used in Alzheimer’s disease. It is sometimes used in certain diseases that cause dizziness or problems with eye movements.
For clinicians
Overview
Memantine is an uncompetitive antagonist at glutamatergic NMDA receptors, inhibiting influx of calcium ions, and may protect against excitotoxicity. It was originally developed for treatment of moderate to severe Alzheimer’s disease, but has also found several off-label uses. In otoneurology it is sometimes used in the management of certain forms of nystagmus.
Introduction
Memantine received FDA approval in the United States for the treatment of Alzheimer’s disease, though it has also been studied (in off-label usage) in autism and bipolar disorder.
Pharmacology
Memantine is an uncompetitive antagonist at glutamatergic NMDA receptors, inhibiting influx of calcium ions. Since glutamate is an excitatory neurotransmitter, and since memantine inhibits glutamatergic NMDA receptors, it is thought to protect neurons against “excitotoxicity,” or excessive stimulation.
Adverse effects
Although some studies describe memantine as well-tolerated (Assarzadegan and Sistanizad 2017), our own experience has been that most patients discontinue the drug due to side effects, often before completing an adequate trial. Reported adverse effects include hypertension, hypotension, weight gain, dyspepsia, nausea/vomiting, constipation or diarrhea, urinary incontinence and a variety of behavioral abnormalities (aggression, confusion, hallucinations).
Cautions and contraindications
Memantine may be relatively contraindicated in patients with cardiovascular disease, hepatic or renal impairment, or seizures.
Relevance in otoneurology
The role of memantine in otoneurology is limited. Several small studies found memantine to be effective in treating:
- Congenital nystagmus (McLean et al. 2007; Shery et al. 2006).
- Periodic alternating nystagmus (Kumar et al. 2009).
- Acquired nystagmus in common variable immunodeficiency with cutaneous sarcoid (Kumar et al. 2009).
- Acquired pendular nystagmus in multiple sclerosis (Starck et al. 2010) or oculopalatal tremor (Nerrant et al. 2020).
- Various forms of acquired nystagmus in multiple sclerosis, stroke and trauma (Thurtell et al. 2010).
- There is also a modest literature regarding memantine in the prophylactic treatment of migraine (Assarzadegan and Sistanizad 2017; Bigal et al. 2008; Charles et al. 2007; Hoffmann and Charles 2018; Huang et al. 2014; Krymchantowski and Jevoux 2009; Mistry et al. 2021; Moreno-Ajona et al. 2021; Noruzzadeh et al. 2016; Rau and Dodick 2019; Shanmugam et al. 2019; Spengos et al. 2008; Xu et al. 2021).
- There is also a report of memantine’s use in superior oblique myokymia (Jain et al. 2008).
References
Assarzadegan F, Sistanizad M (2017) Tolerability and Efficacy of Memantine as Add on Therapy in Patients with Migraine. Iran J Pharm Res 16: 791-797.
Bigal M, Rapoport A, Sheftell F, Tepper D, Tepper S (2008) Memantine in the preventive treatment of refractory migraine. Headache 48: 1337-42. doi: 10.1111/j.1526-4610.2008.01083.x
Charles A, Flippen C, Romero Reyes M, Brennan KC (2007) Memantine for prevention of migraine: a retrospective study of 60 cases. J Headache Pain 8: 248-50.
Hoffmann J, Charles A (2018) Glutamate and Its Receptors as Therapeutic Targets for Migraine. Neurotherapeutics 15: 361-370. doi: 10.1007/s13311-018-0616-5
Huang L, Bocek M, Jordan JK, Sheehan AH (2014) Memantine for the prevention of primary headache disorders. Ann Pharmacother 48: 1507-11. doi: 10.1177/1060028014548872
Jain S, Farooq SJ, Gottlob I (2008) Resolution of superior oblique myokymia with memantine. J AAPOS 12: 87-8. doi: 10.1016/j.jaapos.2007.07.007
Krymchantowski A, Jevoux C (2009) Memantine in the preventive treatment for migraine and refractory migraine. Headache 49: 481-2.
Kumar A, Thomas S, McLean R, Proudlock FA, Roberts E, Boggild M, Gottlob I (2009) Treatment of acquired periodic alternating nystagmus with memantine: a case report. Clin Neuropharmacol 32: 109-10. doi: 10.1097/WNF.0b013e3181873697
McLean R, Proudlock F, Thomas S, Degg C, Gottlob I (2007) Congenital nystagmus: randomized, controlled, double-masked trial of memantine/gabapentin. Ann Neurol 61: 130-8. doi: 10.1002/ana.21065
Mistry VM, Morizio PL, Pepin MJ, Bryan WE, Brown JN (2021) Role of memantine in the prophylactic treatment of episodic migraine: A systematic review. Headache 61: 1207-1213. doi: 10.1111/head.14186
Moreno-Ajona D, Villar-Martinez MD, Goadsby PJ (2021) Targets for migraine treatment: beyond calcitonin gene-related peptide. Curr Opin Neurol 34: 363-372. doi: 10.1097/WCO.0000000000000935
Nerrant E, Abouaf L, Pollet-Villard F, Vie AL, Vukusic S, Berthiller J, Colombet B, Vighetto A, Tilikete C (2020) Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes. J Neuroophthalmol 40: 198-206. doi: 10.1097/WNO.0000000000000807
Noruzzadeh R, Modabbernia A, Aghamollaii V, Ghaffarpour M, Harirchian MH, Salahi S, Nikbakht N, Noruzi N, Tafakhori A (2016) Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study. Headache 56: 95-103. doi: 10.1111/head.12732
Rau JC, Dodick DW (2019) Other Preventive Anti-Migraine Treatments: ACE Inhibitors, ARBs, Calcium Channel Blockers, Serotonin Antagonists, and NMDA Receptor Antagonists. Curr Treat Options Neurol 21: 17. doi: 10.1007/s11940-019-0559-0
Shanmugam S, Karunaikadal K, Varadarajan S, Krishnan M (2019) Memantine Ameliorates Migraine Headache. Ann Indian Acad Neurol 22: 286-290. doi: 10.4103/aian.AIAN_294_18
Shery T, Proudlock FA, Sarvananthan N, McLean RJ, Gottlob I (2006) The effects of gabapentin and memantine in acquired and congenital nystagmus: a retrospective study. Br J Ophthalmol 90: 839-43. doi: 10.1136/bjo.2005.086322
Spengos K, Theleritis C, Paparrigopoulos T (2008) Memantine and NMDA antagonism for chronic migraine: a potentially novel therapeutic approach? Headache 48: 284-6.
Starck M, Albrecht H, Pollmann W, Dieterich M, Straube A (2010) Acquired pendular nystagmus in multiple sclerosis: an examiner-blind cross-over treatment study of memantine and gabapentin. J Neurol 257: 322-7. doi: 10.1007/s00415-009-5309-x
Thurtell MJ, Joshi AC, Leone AC, Tomsak RL, Kosmorsky GS, Stahl JS, Leigh RJ (2010) Crossover trial of gabapentin and memantine as treatment for acquired nystagmus. Ann Neurol 67: 676-80. doi: 10.1002/ana.21991
Xu Z, Chen L, Jin S, Chen X, Yang B (2021) The Efficacy of Memantine for the Treatment of Migraine: A Meta-Analysis of Randomized Controlled Studies. Clin Neuropharmacol 44: 94-98. doi: 10.1097/WNF.0000000000000425
