What is the recommended dosing regimen for amantadine in the treatment of traumatic brain injury?

Amantadine Dosing for Traumatic Brain Injury

For adults with traumatic brain injury, amantadine should be administered at 100 mg twice daily (200 mg total daily dose) to improve cognitive function and reduce irritability. 1

Adult Dosing Protocol

• Standard adult dose: 100 mg twice daily (morning and noon)
• Duration: Treatment for at least 28 days has shown significant benefits 1
• Timing: Can be initiated within the first week after TBI for optimal cognitive improvement 2

Special Population Considerations

Renal Impairment

• For patients with creatinine clearance ≤50 mL/min/1.73m², consult the drug package insert for adjusted dosing 3
• Significant dose reduction is required for severe renal impairment

Elderly Patients (≥65 years)

• Consider starting at 100 mg daily (rather than twice daily) 3
• Monitor closely for side effects and adjust as needed

Pediatric Dosing

• Children 10-12 years: 100 mg twice daily 3
• Children 1-9 years: 5 mg/kg/day up to 150 mg in two divided doses 3
• Children <1 year: Not adequately evaluated, use not recommended 3
• Weight-based adjustment: Children ≥10 years who weigh <40 kg should receive 5 mg/kg/day regardless of age 3, 4

Evidence for TBI-Specific Benefits

Research demonstrates that amantadine provides significant benefits for TBI patients:

• Improves cognitive function with a mean difference of 0.50 (95% CI, 0.33-0.66) compared to controls 2
• Reduces irritability in 80.56% of patients (vs. 44.44% with placebo) 1
• Improves scores on standardized assessments including Mini-Mental Status, Disability Rating Scale, Glasgow Outcome Scale, and FIM Cognitive scores 5
• Shows greatest efficacy when started within the first week after injury 2

Administration Pearls

• Administer in the morning and at noon to minimize sleep disturbances
• May be taken with or without food
• Maintain consistent dosing times to maintain steady blood levels
• For patients with difficulty swallowing, liquid formulations are available

Monitoring

• Assess cognitive function and irritability/aggression at baseline and periodically
• Monitor for adverse effects including insomnia, dizziness, and hallucinations
• No significant difference in adverse event occurrence compared to placebo has been reported 2

Common Pitfalls to Avoid

1. Incorrect weight-based calculations: Always convert pounds to kilograms when calculating pediatric doses 4
2. Evening dosing: Avoid late afternoon or evening dosing which may increase insomnia risk
3. Failure to adjust for renal impairment: Always check creatinine clearance before initiating therapy
4. Inadequate duration: Continue treatment for at least 28 days to achieve optimal benefits 1
5. Suboptimal dosing: The 20 mg/kg dose has shown superior efficacy in animal models compared to both lower (10 mg/kg) and higher (40 mg/kg) doses, suggesting an optimal therapeutic window 6

The evidence strongly supports amantadine as an effective treatment for improving cognitive function and reducing irritability following traumatic brain injury when dosed appropriately.