Increase Memantine Dose to 20mg Daily
The next step for a patient taking memantine 10mg for memory problems is to increase the dose to the target therapeutic dose of 20mg daily (10mg twice daily), as this is the FDA-approved effective dose demonstrated in controlled clinical trials. 1
Dosing Titration Protocol
The current patient is at 10mg daily, which is only halfway through the titration schedule. The FDA-approved dosing algorithm requires:
- Current dose: 10mg/day (5mg twice daily)
- Next step: Increase to 15mg/day (2.5mL and 5mL as separate doses) after at least one week at current dose 1
- Final target: 20mg/day (10mg twice daily or 5mL twice daily) - this is the dose proven effective in clinical trials 1
- Minimum interval between increases: One week 1
Evidence Supporting 20mg as Target Dose
The 20mg daily dose is critical because:
- High-certainty evidence from 14 studies in approximately 3,700 participants with moderate-to-severe Alzheimer's disease demonstrates consistent clinical benefit at 20mg daily across all domains: cognition (3.11 SIB points improvement), global function (0.21 CIBIC+ points), activities of daily living (1.09 ADL19 points), and behavior (1.84 NPI points) 2
- Meta-analyses show memantine 20mg versus placebo produces statistically significant improvements in cognition scores for moderate to severe Alzheimer's disease 3, 4
- The FDA label explicitly states "the dosage shown to be effective in controlled clinical trials is 20mg/day" 1
Clinical Considerations Before Dose Escalation
Assess the following before increasing:
- Renal function: If creatinine clearance is 5-29 mL/min (severe renal impairment), the target dose should be reduced to 5mg twice daily (10mg total daily) 1
- Hepatic function: Use caution in severe hepatic impairment 1
- Current tolerability: Common adverse effects include dizziness (6.1%), headache (5.5%), confusion, and constipation 1, 2
- Medication adherence: Poor adherence is a criterion for considering discontinuation rather than dose escalation 5
When NOT to Increase Dose
Consider discontinuation rather than dose escalation if:
- Clinically meaningful worsening over past 6 months without other contributing factors 5, 3, 4
- No clinically meaningful benefit observed at any time during treatment (no improvement, stabilization, or decreased rate of decline) 5, 3, 4
- Severe or end-stage dementia with dependence in most basic ADLs 5, 3, 4
- Development of intolerable side effects (confusion, dizziness, falls) 5
- Memantine prescribed for non-approved indications (frontotemporal dementia, mild cognitive impairment) 5, 4
Important Exception
If the patient has neuropsychiatric symptoms (psychosis, agitation, aggression) that have improved with memantine, continue treatment even if cognitive decline persists - do not discontinue or avoid dose escalation based solely on cognitive worsening 5, 4
Alternative Consideration: Combination Therapy
If the patient is not already on a cholinesterase inhibitor (donepezil, rivastigmine, or galantamine), combination therapy with memantine plus a cholinesterase inhibitor shows additional benefits on cognition, activities of daily living, global outcome, and behavior compared to either agent alone 4. This should be considered alongside dose optimization.