Can the dose of amantadine (bid: twice a day) for a patient with tremors, currently at 100 mg bid, be increased?

Can Amantadine 100 mg BID Be Increased for Tremors?

No, amantadine should not be increased beyond 100 mg twice daily (200 mg/day total) for tremor management in most patients, and this dose may actually be ineffective for essential tremor specifically. 1, 2

Critical Context: Amantadine and Tremor Type

The effectiveness and safety of dose escalation depends critically on the underlying tremor etiology:

For Essential Tremor (Non-Parkinsonian)

• Amantadine at 100 mg BID has been proven ineffective for essential tremor in controlled trials, with 37.5% of patients actually experiencing worsening postural tremor as an adverse effect. 2
• Increasing the dose would likely increase adverse effects without therapeutic benefit. 2

For Parkinsonian Tremor

• The FDA-approved maximum dose is 400 mg daily in divided doses for Parkinson's disease, though this requires close physician supervision. 1
• The standard therapeutic dose is 100 mg twice daily (200 mg/day total). 1
• Patients not responding optimally at 200 mg/day may benefit from increases up to 300-400 mg daily in divided doses, but only under close medical supervision. 1

Age-Related Dose Restrictions

Patients ≥65 Years Old

• The daily dose should NOT exceed 100 mg total (not 100 mg BID) for elderly patients, regardless of renal function, because renal clearance declines with age. 3, 4
• This is a firm recommendation from the Advisory Committee on Immunization Practices (ACIP), not merely a suggestion. 4
• Elderly women are particularly susceptible to side effects due to smaller average body size. 3
• If your patient is ≥65 years old and currently on 100 mg BID (200 mg/day), the dose should be REDUCED to 100 mg daily, not increased. 3, 4

Patients <65 Years Old

• For younger adults with Parkinson's disease who are not responding to 200 mg/day, the dose may be cautiously increased to 300 mg daily (e.g., 100 mg TID) or even 400 mg daily in divided doses. 1
• This escalation requires close physician supervision due to increased CNS side effects. 1

Renal Function Considerations

Before any dose adjustment, assess creatinine clearance: 1

• CrCl 30-50 mL/min: Maximum 200 mg on day 1, then 100 mg daily thereafter
• CrCl 15-29 mL/min: 200 mg on day 1, then 100 mg every other day
• CrCl <15 mL/min: 200 mg every 7 days
• Hemodialysis: 200 mg every 7 days

Safety Monitoring for Dose Escalation

If proceeding with dose increase (only in appropriate patients <65 years with Parkinson's disease): 5, 1, 6

Monitor closely for CNS toxicity:

• Nervousness, anxiety, insomnia, difficulty concentrating, lightheadedness 5
• Visual hallucinations, delirium, marked behavioral changes, agitation 5
• Myoclonus and asterixis (can occur even at standard doses) 6
• Increased seizure activity in patients with seizure history 3, 5

Alternative Strategy: Dose Cycling

Rather than increasing the dose, consider: 1

• Temporary discontinuation for several weeks followed by reinitiation may restore therapeutic benefit in patients experiencing loss of effectiveness. 1
• This approach avoids the risks associated with higher doses. 1

Common Pitfalls to Avoid

• Assuming "normal" lab values mean elderly patients can tolerate higher doses - age-related pharmacokinetic changes occur regardless of laboratory results. 4
• Increasing amantadine for essential tremor - this is ineffective and may worsen tremor. 2
• Not considering concomitant CNS-active medications - careful observation is required when amantadine is combined with other CNS drugs, especially stimulants. 3
• Failing to assess renal function before dose adjustment - even mild renal impairment requires dose reduction. 3, 1