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

Memantine (Namenda) Treatment for Moderate to Severe Alzheimer's Disease

The recommended treatment for moderate to severe Alzheimer's disease is memantine at a target dose of 20 mg/day, initiated at 5 mg once daily and increased by 5 mg increments weekly until reaching the maintenance dose of 10 mg twice daily. 1

Dosing and Administration

• Start with 5 mg (2.5 mL) once daily 1
• Increase dose in 5 mg increments with a minimum interval of one week between increases 1
• Follow this titration schedule:
  • Week 1: 5 mg (2.5 mL) once daily
  • Week 2: 10 mg/day (2.5 mL twice daily)
  • Week 3: 15 mg/day (2.5 mL and 5 mL as separate doses)
  • Week 4 and beyond: 20 mg/day (5 mL twice daily) 1
• Memantine can be taken with or without food 1
• For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the recommended dose is 5 mg twice daily 1
• Administer with caution to patients with severe hepatic impairment 1

Extended-Release Option

• Memantine extended-release (Namenda XR) is available as a 28 mg once-daily capsule formulation 2
• The extended-release formulation may improve adherence through a more convenient dosage regimen and lower pill burden 2
• Capsules may be opened and contents sprinkled on applesauce for patients with difficulty swallowing 2

Clinical Efficacy

• Memantine shows statistically significant improvements in cognition as measured by the Severe Impairment Battery (SIB) in moderate to severe Alzheimer's disease 3, 4
• Global assessment improvements are demonstrated on the CIBIC-plus scale 3, 4
• Benefits include improved quality of life and reduced agitation compared to placebo 3
• Memantine can be used as monotherapy or in combination with cholinesterase inhibitors 3, 5, 4
• Combination therapy with memantine plus a cholinesterase inhibitor has shown superior outcomes compared to cholinesterase inhibitor therapy alone 3, 5, 4, 6

Adverse Effects

• Common adverse events include dizziness, headache, confusion, and constipation 1
• Other reported adverse effects include nausea, diarrhea, and agitation 4
• Withdrawal rates due to adverse effects range from 9-12% in treatment groups (compared to 7-13% in placebo groups) 3, 4
• Conditions that raise urine pH may decrease urinary elimination of memantine, resulting in increased plasma levels 1

Treatment Duration and Discontinuation

• Consider discontinuation if:
  • Clinically meaningful worsening of dementia occurs over 6 months without other contributing factors 3, 5, 4
  • No clinical benefit is observed during treatment 3, 5, 4
  • Patient progresses to severe or end-stage dementia with dependence in most basic activities of daily living 3, 5, 4
• When discontinuing, use a gradual approach, reducing dose by 50% every 4 weeks until reaching the initial starting dose 3, 4
• For patients with neuropsychiatric symptoms (psychosis, agitation, aggression), continue memantine if there has been a clinically meaningful reduction in these symptoms, even with cognitive and functional decline 3, 4

Special Considerations

• Memantine is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation 1
• If a patient misses a single dose, they should not double up on the next dose but take it as scheduled 1
• If treatment is interrupted for several days, dosing may need to be resumed at lower doses and retitrated as described above 1