What is the recommended dosage of Memantine (Memantine Hydrochloride) for moderate to severe Alzheimer's disease?

Memantine Dosing for Moderate to Severe Alzheimer's Disease

The recommended dosing regimen for memantine in moderate to severe Alzheimer's disease is to start with 5 mg once daily, then increase by 5 mg increments weekly to a target maintenance dose of 20 mg/day (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 to:
  • Week 2: 10 mg/day (5 mg twice daily) 1
  • Week 3: 15 mg/day (5 mg and 10 mg as separate doses) 1
  • Week 4: 20 mg/day (10 mg twice daily) - maintenance dose 1
• Minimum recommended interval between dose increases is one week 1
• Memantine can be taken with or without food 1

Special Populations

• For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the recommended target dose is 5 mg twice daily (10 mg/day) 1
• For patients with severe hepatic impairment, memantine should be administered with caution 1

Administration Considerations

• If a patient misses a single dose, they should not double up on the next dose 1
• If treatment is interrupted for several days, dosing may need to be resumed at lower doses and retitrated as described above 1
• Memantine oral solution should not be mixed with any other liquid 1

Extended-Release Formulation

• Memantine extended-release is available as a 28 mg once-daily capsule formulation 2
• The extended-release formulation may offer advantages including:
  • More convenient once-daily dosing 2
  • Lower pill burden that may improve adherence 2
  • Option to open capsules and sprinkle contents on applesauce for patients with difficulty swallowing 2

Clinical Efficacy

• Memantine has demonstrated statistically significant improvement in cognition scores for moderate to severe Alzheimer's disease as measured by the Severe Impairment Battery (SIB) 3, 4
• Studies show significant changes on the CIBIC-plus scale (global assessment) for patients with moderate to severe Alzheimer's disease 3, 5
• Limited evidence shows improvement in quality of life, caregiver burden, and resource utilization 3
• Combination therapy with cholinesterase inhibitors has shown additional benefits, with patients receiving memantine plus donepezil showing significant benefits on measures of cognition, activities of daily living, global outcome, and behavior compared to donepezil alone 4, 6

Adverse Effects

• Common adverse events include dizziness, headache, confusion, and constipation 1
• Withdrawal rates due to adverse effects range from 9-12% in treatment groups (compared to 7-13% in placebo groups) 3

Duration of Treatment and Discontinuation

• Consider discontinuation if there has been clinically meaningful worsening of dementia over the past 6 months without other medical conditions or environmental factors contributing to the decline 7
• Consider discontinuation if no clinically meaningful benefit observed at any time during treatment 7
• Consider discontinuation if the individual has severe or end-stage dementia (dependence in most basic activities of daily living, inability to respond to environment, or limited life expectancy) 7
• When discontinuing memantine, a gradual approach is recommended, reducing dose by 50% every 4 weeks until reaching the initial starting dose 7

Important Clinical Considerations

• Memantine is specifically indicated for moderate to severe dementia of the Alzheimer's type 1
• Conditions that raise urine pH may decrease the urinary elimination of memantine, resulting in increased plasma levels 1
• For patients with neuropsychiatric symptoms (psychosis, agitation, aggression), continue memantine if there has been a clinically meaningful reduction in these symptoms, even if there is evidence of cognitive and functional decline 7, 3