Q&A 396.2
Is memantine effective in the treatment of nystagmus?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
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Date prepared: 31st March 2014
Background
Nystagmus is a disorder of the eyes in which fast, uncontrollable movements of the eyeball occur[1]. Usually, vision is not affected, and the patient may not be aware of the movements. Some patients, particularly in cases of acquired nystagmus, can experience blurred vision and oscillopsia which can interfere with their quality of life[2],[3] Nystagmus may have a variety of causes including congenital, trauma, and multiple sclerosis (MS)[4]. A number of drug treatment strategies, including antiepileptics, botulinum toxin, alcohol, and tetrahydrocannabinol have been used for treatment of acquired nystagmus, although no cure exists4,[5]. Non-pharmacological treatment can include use of prisms and filters, or surgery4,5.
Memantine is an NMDA receptor antagonist licensed for the treatment of moderate to severe Alzheimer’s disease. Its use as a treatment for nystagmus is an unlicensed indication[6].
Answer
Proposed mechanism:
The aim of treatment for nystagmus is to reduce or abolish the movements of the eye, stabilising vision and reducing symptoms3. The glutaminergic action of memantine is thought to be responsible for its action in nystagmus[7], but the exact mechanism is currently unknown[8].
Types of nystagmus:
Acquired Nystagmus
Thurtell et al conducted a crossover trial of gabapentin vs memantine for treatment of acquired nystagmus. The trial was limited by its short duration (2 weeks for each drug, with a 2-3 week washout period in between) and its small size (n=10). The trial found a significant increase in visual acuity with both drugs, along with an average reduction in median eye speed of 27.8% with memantine, with a 32.8% reduction with gabapentin. The authors report that “the effects of the drugs were idiosyncratic and unrelated to the aetiology or waveform of nystagmus”3.
In a case report by Kumar et al, the treatment of a 46 year old male with acquired periodic alternating nystagmus with memantine was described. He had been receiving baclofen treatment with mild symptom improvement. After 4 months of memantine 20mg, nystagmus was clearly reduced, with subjective, patient reported improvements in oscillopsia and visual acuity of 80% compared to 20% with baclofen. The patient’s best corrected visual acuity scores (measured during the quiet phase of his nystagmus) went from 6/6 in both eyes to 6/6 in the right eye and 6/4 in the left8.
Multiple Sclerosis
Acquired fixational pendular nystagmus (APN) can be a particularly distressing symptom of multiple sclerosis (MS)5. Nystagmus caused by MS may be horizontal, vertical, or mixed[9].
Eleven patients were treated with memantine in a study looking at memantine, scopolamine, and mexiletine use in APN due to MS. Memantine was found to be effective in all 11 patients, with doses ranging between 15mg- 60mg. Whilst the trial duration was very short (7 days), the authors reported that six patients with APN had been followed for one to three years following the trial. They had been taking memantine during the follow up period, with at least one session of discontinuation of memantine. Discontinuation caused worsening of oscillopsia in all patients9.
A further 11 patients with a total of 20 affected eyes underwent an examiner blind cross-over trial comparing the effectiveness of memantine and gabapentin in APN due to MS. This study found a reduction of nystagmus of at least 50% with memantine treatment in 17 out of the 20 affected eyes, with complete cessation in eight eyes at a dose of 40mg and a further four eyes with a 60mg dose5.
Three patients in the study by Thurtell et al (described above) had acquired pendular nystagmus due to MS. It was found that 2 of these patients, neither memantine nor gabapentin had any effect on nystagmus frequency, but APN did improve with both drugs3.
A retrospective study reported on the use of memantine in four patients. These were patients in whom gabapentin treatment had failed. It was shown that in the three patients whose nystagmus was secondary to MS, visual acuity and nystagmus amplitude improved. However, one patient whose nystagmus was caused by spinocerebellar ataxia found no improvement in oscillopsia or nystagmus amplitude with use of memantine. The authors of this study concluded that memantine “is a strong candidate for treatment of nystagmus in MS”7.
Limitations of use of memantine in patients with MS include adverse reactions such as fatigue and dizziness, and memantine has been reported as exacerbating the symptoms of MS3.
Congenital Nystagmus:
There are few cases describing treatment of congenital nystagmus in the literature.
McLean et al undertook a randomized, double masked trial assessing the effects of memantine or gabapentin in 48 cases of congenital nystagmus. The study found that congenital idiopathic nystagmus (CIN) appeared to respond well to pharmacological treatment, but only small improvements occurred in patients with secondary nystagmus (SN). Visual acuity in patients with CIN improved by 22.2%(+/- 8.5%) and 5.8% (+/- 1.8%) in patients with SN. No significant difference was found between the effectiveness of memantine and gabapentin, but both were significant when compared to placebo in CIN. Whilst no significant improvements were found in SN, patients subjectively reported an improvement and many chose to continue with treatment after the study period had ended[10].
Summary
Nystagmus has a varied range of causes, some of which are rare and poorly understood. This has made it difficult to pinpoint effective treatments for the potentially distressing symptoms of nystagmus5,7,8,9.
Memantine is a treatment option for the treatment of nystagmus, particularly where gabapentin is ineffective. It may be particularly effective in cases of nystagmus caused by MS, but more research needs to be done in this area, and the potential of memantine to exacerbate MS needs to be borne in mind3,7.
Whilst a robust evidence base is lacking, memantine may be an effective option in some patients. The apparently idiosyncratic nature of the drug’s effects suggests that it may work in patients in whom other therapies have failed3.
Limitations
Evidence for treatments of nystagmus is limited due to the varied and potentially rare nature of the disease state. All trials for memantine are of relatively short duration and are small.
Quality Assurance
Prepared by
Hayley Johnson, Regional Drug & Therapeutics Centre
Date Prepared
31st March 2014
Checked by
Nancy Kane, Regional Drug & Therapeutics Centre
Date of check
31st March 2014
Search strategy
Embase
*MEMANTINE/ AND *NYSTAGMUS/
Medline
*MEMANTINE/ AND [*NYSTAGMUS, CONGENITAL/ OR *NYSTAGMUS, OPTOKINETIC/ OR *NYSTAGMUS, PATHOLOGIC/ OR *NYSTAGMUS, PHYSIOLOGIC/]
DrugDex
Summary of Product Characteristics
In-house databases
References
2
Available through NICE Evidence Search at www.evidence.nhs.uk
[1] National Library of Health: Eye Movement Disorders Health Topic Page: Medline Plus Accessed via http://www.nlm.nih.gov/medlineplus/eyemovementdisorders.html on 31/03/2014
[2] What is nystagmus? American Academy of Opthalmology: Accessed via http://www.geteyesmart.org/eyesmart/diseases/index.cfm on 31/03/2014
[3] Thurtell MJ, Joshi AC, Leone AC, et al. Cross-over trial of gabapentin and memantine as treatment for acquired nystagmus. Annals of Neurology 2010; 67(5): 676-680.
[4] Scott O. Nystagmus: Patient.co.uk PatientPlus Information. Accessed via http://www.patient.co.uk/doctor/Nystagmus.htm on 31/03/2014
[5] Starck M, Albrecht H, Pollmann W et al. Acquired pendular nystagmus in multiple sclerosis: an examiner-blind cross-over treatment study of memantine and gabapentin. J Neurol 2010; 257: 322-327.
[6] Summary of Product Characteristics last updated on the eMC: 24/05/2012 Ebixa 5mg/pump actuation oral solution, 20mg and 10 mg Tablets and Treatment Initiation Pack Lundbeck. Accessed via http://www.medicines.org.uk/EMC/medicine/10175/SPC/Ebixa+5mg+pump+actuation+oral+solution%2c+20mg+and+10+mg+Tablets+and+Treatment+Initiation+Pack/ on 31/03/2014
[7] Shery T, Proudlock FA, Sarvananthan N et al. The effects of gabapentin and memantine in acquired and congenital nystagmus: a retrospective study. Br J Opthalmol 2006; 90: 839-843.
[8] Kumar A, Thomas S, McLean R et al. Treatment of Acquired Periodic Alternating Nystagmus with memantine: a case report. Clinical Neuropharmacology 2009; 32(2): 109-110.
[9] Starck M, Albrecht H, Pollman W et al. Drug therapy for acquired pendular nystagmus in multiple sclerosis. J Neurol 1997; 244: 9-16
[10] McLean R, Proudlock F, Thomas S et al. Congenital nystagmus: randomised, controlled, double-masked trial of memantine/gabapentin. Ann Neurol 2007; 61:130-138.