Is amantadine (Amantadine) used to treat ataxia in Multiple System Atrophy (MSA)?

Amantadine for Ataxia in Multiple System Atrophy

Amantadine can be used to treat ataxia in MSA patients, with evidence showing approximately 60% of MSA patients respond to this therapy, though the effect is typically modest and temporary. 1, 2

Evidence for Amantadine Use in MSA-Related Ataxia

Clinical Efficacy Data

The strongest evidence comes from a 2012 open-label study demonstrating that intravenous amantadine (400 mg/day for 5 days) significantly reduced ataxia severity in MSA-C patients, with mean International Cooperative Ataxia Rating Scale scores improving from 42.5 to 37.3 (p < 0.001). 2 Key findings include:

• All 20 patients reported subjective improvement on patient global impression scales 2
• In responders (approximately 35% of treated patients), the beneficial effect lasted more than 1 month in 4 out of 7 cases 2
• No side effects were observed with intravenous administration 2

Supporting Evidence from Related Conditions

Amantadine has demonstrated efficacy for cerebellar ataxia in other neurodegenerative conditions:

• In olivopontocerebellar atrophy (OPCA), which shares pathophysiological features with MSA-C, amantadine 200 mg/day produced striking improvements in both reaction time and movement time (7 out of 8 measures improved) 3
• A 1997 retrospective analysis found 61.5% of MSA patients improved with amantadine 100 mg twice daily, though adverse effects occurred in 23.1% of cases 4

Practical Treatment Approach

Dosing Strategy

Start with oral amantadine 100 mg twice daily (200 mg/day total), as this is the most commonly studied dose with acceptable tolerability. 1, 4

• For patients who respond but need additional benefit, consider intravenous amantadine 400 mg/day for 5 days as a trial, recognizing this requires hospitalization or infusion center access 2
• The mechanism of benefit is unclear but likely relates to NMDA antagonist properties rather than dopaminergic effects 4

Important Caveats

Amantadine is significantly less effective for ataxia than for parkinsonian features in MSA, and response is unpredictable. 1 Critical considerations include:

• Unlike levodopa (which benefits 40-60% of MSA-P patients), amantadine shows variable and generally modest effects 1
• CNS side effects occur in approximately 13% of patients at standard dosing (200 mg/day), including nervousness, anxiety, insomnia, and lightheadedness 5
• Older patients and those with seizure disorders or psychiatric conditions are at higher risk for serious CNS toxicity and may require dose reduction 5
• Anticholinergic effects can cause urinary retention and should not be used in untreated angle-closure glaucoma 5

Monitoring and Duration

Assess response after 2-4 weeks of treatment using objective ataxia scales (such as ICARS) and patient-reported outcomes. 2

• If no benefit is observed by 3 months, discontinuation is reasonable 3
• Most side effects are mild and resolve within the first week or upon discontinuation 5
• The duration of benefit is variable; some patients maintain improvement for only weeks while others may benefit for months 2

Clinical Context

Amantadine remains a reasonable symptomatic treatment option for MSA-related ataxia given the lack of disease-modifying therapies and the generally favorable safety profile. 1, 2 However, expectations should be tempered:

• The treatment is purely symptomatic and does not alter disease progression 1
• Response rates are lower than for parkinsonian features in MSA 1
• The mechanism of action in cerebellar ataxia remains unclear 2