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
  • 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.
• Target doses: ranged from 900 mg/day up to 2,400 mg/day
  • Thurtell crossover trial used1,200 mg/day
  • Nerrant trial used **300 mg four times daily (1,200 mg/day)
  • EFNS review cites benefit at doses up to 2,400 mg/day
  • Averbuch-Heller trial used up to 900 mg/day
• 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
  • 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

• Titrate up over 1-3 weeks
  • Conventional approach is to start 5 mg/day and increase by 5 mg/week to 20 mg/day
  • Further escalation toward 40 (to 60) mg/day is done gradually and only as tolerated
  • Target doses studied
    • 40 mg/day in most trials (Thurtell, EFNS)
    • 10 mg four times daily (40 mg/day) in Nerrant
    • 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
• Renal dosing: reduce dose in severe renal impairment.
• Key adverse effects/monitoring
  • Lethargy and drowsiness are most common
  • Dizziness, confusion, and headache
  • Discontinuation was higher than gabapentin (~18.8%, including one serious adverse event).
  • In MS: may worsen MS symptoms and cognition in MS patients gabapentin is preferred first-line, and if memantine is used, select patients without significant cognitive impairment and titrate cautiously

• Efficacy endpoints
  • Near and distance visual acuity
  • Patient-reported oscillopsia
  • Reduction on eye-movement recording/EOG when available.
  • Trials targeted a ≥50% reduction in nystagmus amplitude/frequency
• Tolerability
  • Assess gait/ataxia, sedation, and cognition at each dose step;
  • Renal function guides dosing for both drugs.
• Approach
  • do an individual trial of one drug, then the other (and sometimes combination or dose reduction to minimize side effects)
  • Effects appear within the ~2-week windows used in trials, so each agent can be assessed over a few weeks

• 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.