What medication adjustment is recommended for a patient with Alzheimer's disease (AD) who shows no improvement on donepezil (Aricept) after 6 months, with magnetic resonance imaging (MRI) evidence of cortical atrophy?

Add Memantine to Donepezil

For a patient with Alzheimer's disease showing no improvement after 6 months on donepezil, add memantine to the existing donepezil regimen rather than switching medications. 1, 2

Rationale for Adding Memantine

The evidence strongly supports combination therapy in this clinical scenario:

• Memantine demonstrates statistically significant benefits in moderate to severe Alzheimer's disease, particularly on the Severe Impairment Battery (SIB) and CIBIC-plus scales, with improvements in cognition, global assessment, and quality of life 3

• Combination therapy (donepezil plus memantine) produces superior outcomes compared to cholinesterase inhibitor monotherapy alone, with significant improvements in cognition (mean difference -5.01 on ADAS-Cog), global assessment (mean difference -2.88), daily activities (mean difference 13.06), and neuropsychiatric symptoms (mean difference -6.84) 4

• FDA-approved evidence demonstrates that adding memantine to stable donepezil therapy (in patients on donepezil for at least 6 months) resulted in statistically significant improvements: mean difference of 1.6 units on ADCS-ADL and 3.3 units on SIB at 24 weeks 2

Why Not Switch Medications

Switching from donepezil to rivastigmine (Option D) lacks strong evidence for this specific scenario:

• The 2017 consensus guidelines suggest rivastigmine may offer additive benefit specifically in rapid cognitive decliners (patients declining >3 MMSE points in 6 months), particularly those with vascular risk factors 3

• Your patient has been stable (no improvement but presumably not rapid decline) for 6 months, which does not meet rapid decliner criteria 3

• Switching to memantine monotherapy (Option C) would eliminate the established cholinesterase inhibitor therapy, which continues to provide benefit even in moderate-to-severe disease 5

Implementation Strategy

Initiate memantine while continuing donepezil:

• Start memantine at 5 mg once daily 2
• Increase weekly by 5 mg/day in divided doses to target dose of 20 mg/day (10 mg twice daily) 2
• Maintain donepezil at current therapeutic dose 1, 2

Expected Outcomes

Combination therapy is both rational and safe, with withdrawal rates due to adverse effects of 9-12% (comparable to 7-13% with placebo) 3:

• Primary adverse effects include nausea, dizziness, diarrhea, and agitation 3
• The combination is well-tolerated according to American Geriatrics Society guidelines 1
• Benefits include reduced caregiver burden and improved resource utilization 3

Why Not Sertraline

Adding sertraline (Option A) is not indicated unless the patient has comorbid depression, which is not mentioned in this clinical scenario 3

Monitoring and Reassessment

Evaluate response at 6 months:

• Consider discontinuation if clinically meaningful worsening occurs over 6 months without other contributing factors 1
• Continue memantine if there is clinically meaningful reduction in neuropsychiatric symptoms (psychosis, agitation, aggression), even with cognitive and functional decline 1
• If discontinuing, reduce dose by 50% every 4 weeks until reaching initial starting dose 1

The correct answer is B: Add memantine to the existing donepezil regimen.