Pharmacologic Treatment of Oscillopsia from Nystagmus

• Recommendation depends on the type of nystagmus since drug efficacy differs substantially between nystagmus types.
• Evidence base is limited (small crossover RCTs and case series, mostly very low-certainty)
• Treatment is symptomatic—aimed at reducing slow-phase eye velocity to improve visual acuity and abolish illusory motion
• No agent reliably abolishes nystagmus, effect sizes are modest, and most data come from very small studies—so treatment is often individualized with trial-and-error
• Monitoring for ataxia, fatigue, and dizziness

Often from multiple sclerosis or oculopalatal tremor:

• Gabapentin (typically up to ~2400 mg/day; trial doses 300 mg four times daily)
• Memantine (up to 40–60 mg/day)
  • In a 47-patient placebo-controlled trial gabapetin and memantine were superior to placebo and improved visual acuity, and a double-masked crossover trial found both effective at reducing eye speed and improving acuity, with individual patients responding better to one or the other.[3][2]
  • Gabapentin is generally preferred first-line on tolerability grounds—memantine caused more discontinuations (18.8% vs 6.7%) and can exacerbate MS symptoms, whereas gabapentin was better tolerated.[4][2]
• Topiramate (e.g., 50 mg twice daily) has produced dramatic improvement in refractory APN in a case report when gabapentin/memantine were only partially effective.[5]
• Anticholinergics (trihexyphenidyl, transdermal scopolamine) are largely ineffective and not recommended; results have been inconsistent.[3][2]

• Titrate up over 1-3 weeks
• Assess efficacy by visual acuity, oscillopsia and eye movement recordings if available

- Target doses studied: ranged from 900 mg/day up to 2,400 mg/day. The Thurtell crossover trial used 1,200 mg/day; the Nerrant trial used 300 mg four times daily (1,200 mg/day); the EFNS review cites benefit at doses up to 2,400 mg/day; the earlier Averbuch-Heller trial used up to 900 mg/day.[3][1][4][5] - Titration: start low (e.g., 300 mg/day) and increase every few days as tolerated toward 1,200 mg/day divided TID–QID, going higher (up to ~2,400 mg/day) if partial response and well tolerated. In refractory cases doses as high as 1,800 mg three times daily have been used before adding another agent.[6] - Renal dosing: gabapentin is renally cleared and requires dose reduction in renal impairment (a critical safety point in older or MS patients with bladder/renal issues). - Key adverse effects/monitoring: unsteadiness/ataxia is the main dose-limiting effect—especially in patients with pre-existing cerebellar ataxia—along with somnolence, dizziness, and peripheral edema. Monitor gait and sedation at each titration step; overall it was the better-tolerated drug, with only ~6.7% discontinuing.[1][3]

• Titrate up over 1-3 weeks
• Assess efficacy by visual acuity, oscillopsia and eye movement recordings if available

- Target doses studied: 40 mg/day in most trials (Thurtell, EFNS); 10 mg four times daily (40 mg/day) in Nerrant; and 40–60 mg/day in the Starck MS study, where 60 mg added benefit in some patients. Note these exceed the standard Alzheimer maximum of 20 mg/day, so higher doses are off-label and titrated cautiously.[4][3][1][2] - Titration: conventional approach is to start 5 mg/day and increase by 5 mg/week to 20 mg/day; for nystagmus, further escalation toward 40 (–60) mg/day is done gradually and only as tolerated.[7][2] - Renal dosing: reduce dose in severe renal impairment. - Key adverse effects/monitoring: lethargy and drowsiness are most common; also dizziness, confusion, and headache. Discontinuation was higher than gabapentin (~18.8%, including one serious adverse event). Critically, memantine has been reported to worsen MS symptoms and cognition, so in MS patients gabapentin is preferred first-line, and if memantine is used, select patients without significant cognitive impairment and titrate cautiously.[1][3][7]

Monitoring parameters common to both

- Efficacy endpoints: near and distance visual acuity (LogMAR), patient-reported oscillopsia, and objective nystagmus reduction on eye-movement recording/EOG when available. Trials targeted a ≥50% reduction in nystagmus amplitude/frequency as a benchmark.[1][2] - Tolerability: assess gait/ataxia, sedation, and cognition at each dose step; renal function guides dosing for both drugs. - Approach: because response is idiosyncratic and unrelated to nystagmus etiology or waveform, an individual trial of one drug, then the other (and sometimes combination or dose reduction to minimize side effects), is standard. Effects appear within the ~2-week windows used in trials, so each agent can be assessed over a few weeks.[1][3]

ParameterGabapentinMemantineReferencesStarting dose300 mg/day5 mg/day[1], [2], [7]Titration↑ every few days as tolerated↑ 5 mg/week[2], [7]Target dose (APN)1,200 mg/day (up to 2,400) divided TID–QID40 mg/day (up to 60)[1], [2], [3], [4]Main adverse effectsAtaxia/unsteadiness, somnolence, edemaLethargy/drowsiness, dizziness, confusion[1], [3]Discontinuation rate (Nerrant)~6.7%~18.8%[1]Renal impairmentDose reduceDose reduce (severe)—MS-specific cautionPreferred first-lineMay worsen MS symptoms/cognition[3], [7]

• Aminopyridines
  • 4-aminopyridine (potassium channel blocker)
  • 3,4-diaminopyridine
  • Reduce slow-phase velocity and oscillopsia (two RCTs support use), with 4-AP possibly more potent;
  • the main side effect is transient perioral/distal paresthesia.[1][6]

• Memantine- jerk nystagmus responds less well to medication than others

• Baclofen (up to ~30 mg/day)

1. Interventions for Eye Movement Disorders Due to Acquired Brain Injury. Rowe FJ, Hanna K, Evans JR, et al. The Cochrane Database of Systematic Reviews. 2018;3:CD011290. doi:10.1002/14651858.CD011290.pub2.
2. Crossover trial of gabapentin and memantine as treatment for acquired nystagmus. Thurtell MJ, Joshi AC, Leone AC, et al. Annals of Neurology. 2010;67(5):676-80. doi:10.1002/ana.21991.
3. Nystagmus and oscillopsia. Straube A, Bronstein A, Straumann D, European Federation of Neurologic Societies. European Journal of Neurology. 2012;19(1):6-14. doi:10.1111/j.1468-1331.2011.03503.x.
4. Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes. Nerrant E, Abouaf L, Pollet-Villard F, et al. Journal of Neuro-Ophthalmology : The Official Journal of the North American Neuro-Ophthalmology Society. 2020;40(2):198-206. doi:10.1097/WNO.0000000000000807.
5. Teaching Video NeuroImage: Dramatic Response to Topiramate in Acquired Pendular Nystagmus From Multiple Sclerosis. Murphy OC, Calabresi PA, Gold DR. Neurology. 2023;100(1):47-48. doi:10.1212/WNL.0000000000201452.
6. Pharmacotherapy of Vestibular and Cerebellar Disorders and Downbeat Nystagmus: Translational and Back-Translational Research. Strupp M, Zwergal A, Feil K, Bremova T, Brandt T. Annals of the New York Academy of Sciences. 2015;1343:27-36. doi:10.1111/nyas.12774.
7. Pharmacotherapy of Vestibular Disorders and Nystagmus. Strupp M, Kremmyda O, Brandt T. Seminars in Neurology. 2013;33(3):286-96. doi:10.1055/s-0033-1354594.
8. Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes. Nerrant E, Abouaf L, Pollet-Villard F, et al. Journal of Neuro-Ophthalmology : The Official Journal of the North American Neuro-Ophthalmology Society. 2020;40(2):198-206. doi:10.1097/WNO.0000000000000807.
9. Acquired Pendular Nystagmus in Multiple Sclerosis: An Examiner-Blind Cross-Over Treatment Study of Memantine and Gabapentin. Starck M, Albrecht H, Pöllmann W, Dieterich M, Straube A. Journal of Neurology. 2010;257(3):322 7. doi:10.1007/s00415-009-5309-x.
10. Crossover trial of gabapentin and memantine as treatment for acquired nystagmus. Thurtell MJ, Joshi AC, Leone AC, et al. Annals of Neurology. 2010;67(5):676-80. doi:10.1002/ana.21991.
11. Nystagmus and oscillopsia. Straube A, Bronstein A, Straumann D, European Federation of Neurologic Societies. European Journal of Neurology. 2012;19(1):6-14. doi:10.1111/j.1468-1331.2011.03503.x.
12. A Double-Blind Controlled Study of Gabapentin and Baclofen as Treatment for Acquired Nystagmus. Averbuch-Heller L, Tusa RJ, Fuhry L, et al. Annals of Neurology. 1997;41(6):818-25. doi:10.1002/ana.410410620.
13. Teaching Video NeuroImage: Dramatic Response to Topiramate in Acquired Pendular Nystagmus From Multiple Sclerosis. Murphy OC, Calabresi PA, Gold DR. Neurology. 2023;100(1):47-48. doi:10.1212/WNL.0000000000201452.
14. Pharmacological Management of Symptoms in Multiple Sclerosis: Current Approaches and Future Directions. Thompson AJ, Toosy AT, Ciccarelli O. The Lancet. Neurology. 2010;9(12):1182-1199. doi:10.1016/S1474-4422(10)70249-0.