What is the preferred treatment between modafinil (Provigil) and amantadine for abulia?

Modafinil vs Amantadine for Abulia

Modafinil is preferred over amantadine for the treatment of abulia due to its more favorable efficacy profile and fewer central nervous system side effects. 1

Comparison of Medications

Modafinil

• Mechanism of Action: Acts as a neurostimulant with wake-promoting properties
• Efficacy: Demonstrated positive response in 83% of publications for post-stroke neurocognitive recovery 1
• Dosing:
  • Initial dose: 100 mg daily
  • Maintenance dose: 200 mg daily (range 100-350 mg/day)
  • Can be titrated based on response

Amantadine

• Mechanism of Action: NMDA receptor antagonist with dopaminergic effects
• Efficacy: Showed positive response in 70% of publications for post-stroke cognitive recovery 1
• Dosing:
  • Initial dose: 100 mg once or twice daily
  • Maintenance dose: 200 mg daily (range 100-300 mg/day)
  • Requires dose adjustment in elderly and those with renal impairment 2

Side Effect Profile Comparison

Modafinil Side Effects

• Dizziness (5% of patients)
• Dry eyes/mouth (5% of patients)
• Less CNS side effects compared to amantadine 1

Amantadine Side Effects

• Visual hallucinations (2% of patients) 1
• Higher incidence of CNS side effects including:
  • Nervousness, anxiety, insomnia, difficulty concentrating (13% of patients) 2
  • Confusion and seizures in elderly or those with renal disease 2
  • Requires dose reduction in elderly to ≤100 mg/day 2

Treatment Algorithm for Abulia

1. First-line treatment: Modafinil

   • Start at 100 mg daily
   • Titrate to 200 mg daily based on response
   • Monitor for dizziness and dry mouth

2. Alternative if modafinil fails or is contraindicated: Amantadine

   • Start at 100 mg daily
   • May increase to 100 mg twice daily if tolerated
   • Maximum dose 200 mg/day
   • Reduce dose to 100 mg/day in elderly or those with renal impairment

3. Monitoring parameters:

   • Improvement in initiation of activities
   • Participation in therapy
   • Functional independence measures

Special Considerations

Renal Impairment

• Modafinil: No specific dose adjustments required
• Amantadine: Significant dose reductions required 2
  • For creatinine clearance <50 mL/min: Reduce dose according to package insert
  • For creatinine clearance <10 mL/min: Significant dose reduction required

Elderly Patients

• Modafinil: No specific dose adjustments required based on age alone 2
• Amantadine: Daily dosage should not exceed 100 mg for both prophylaxis and treatment 2

Seizure Risk

• Modafinil: Seizure events reported but no increased risk established 2
• Amantadine: Increased incidence of seizures in patients with history of seizure disorders 2

Evidence Quality Assessment

The evidence supporting modafinil for abulia comes from systematic reviews examining neurostimulants in post-stroke care 1. While the research specifically on abulia is limited, modafinil shows a higher percentage of positive responses (83% vs 70% for amantadine) and fewer CNS side effects, making it the preferred choice despite both medications showing potential benefit.

The N-of-1 study on amantadine for amotivational syndrome after traumatic brain injury 3 showed some benefit, but the evidence for modafinil is more robust in terms of cognitive improvement with fewer side effects.