What is the recommended dosage and treatment regimen for memantine (Memantine) in patients with moderate to severe Alzheimer's disease?

Memantine Dosage and Treatment Regimen for Moderate to Severe Alzheimer's Disease

The recommended dosing regimen for memantine in moderate to severe Alzheimer's disease is to start at 5 mg once daily and increase by 5 mg increments weekly to a target maintenance dose of 20 mg/day (administered as 10 mg twice daily). 1

Initial Dosing and Titration Schedule

• Start with 5 mg (2.5 mL oral solution) once daily 1
• Increase dose in 5 mg increments with a minimum interval of one week between increases 1
• Week 1: 5 mg (2.5 mL) once daily 1
• Week 2: 10 mg/day (2.5 mL twice daily) 1
• Week 3: 15 mg/day (2.5 mL and 5 mL as separate doses) 1
• Week 4 and beyond: 20 mg/day (5 mL twice daily) - this is the effective maintenance dose established in clinical trials 1

Administration Guidelines

• Memantine can be taken with or without food 1
• If a dose is missed, the patient should not double up; the next dose should be taken as scheduled 1
• If treatment is interrupted for several days, dosing should be resumed at lower doses and retitrated as described above 1
• For oral solution: use the provided dosing syringe, do not mix with other liquids 1

Special Populations

• Renal impairment: For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the recommended target dose is reduced to 5 mg twice daily (10 mg/day total) 1
• Hepatic impairment: Administer with caution to patients with severe hepatic impairment 1

Efficacy and Duration of Treatment

• Memantine improves cognition and global function in moderate to severe Alzheimer's disease, with consistent evidence from multiple trials 2, 3
• Memantine is well tolerated both as monotherapy and in conjunction with cholinesterase inhibitors such as donepezil 2, 4
• Combination therapy with memantine plus donepezil shows significant benefits on measures of cognition, activities of daily living, global outcome, and behavior compared to donepezil alone 3, 4
• Clinical trials have demonstrated efficacy for up to 28 weeks, but long-term benefit beyond this period is less well established 2

Monitoring and Discontinuation Considerations

• Consider discontinuation if:

  • Clinically meaningful worsening of dementia over 6 months without other contributing factors 3
  • No clinically meaningful benefit observed during treatment 3
  • Patient progresses to severe or end-stage dementia with dependence in most basic activities of daily living 3

• When discontinuing memantine, a gradual approach is recommended, reducing dose by 50% every 4 weeks until reaching the initial starting dose 3

Common Adverse Effects

• Most common adverse events include dizziness, headache, confusion, and constipation 1
• Other reported adverse events include nausea, diarrhea, and agitation 3, 1
• Withdrawal rates due to adverse events range from 7.4% with memantine compared to 12.4% with placebo 4
• Memantine may actually reduce agitation compared to placebo in some studies 2, 3

Clinical Considerations

• Conditions that raise urine pH may decrease urinary elimination of memantine, potentially increasing plasma levels 1
• For patients with neuropsychiatric symptoms (psychosis, agitation, aggression), continue memantine if there has been a clinically meaningful reduction in these symptoms 3