Medication Adjustment for Non-Response to Donepezil
Add memantine to the existing donepezil regimen rather than switching or substituting medications. 1, 2, 3
Rationale for Adding Memantine
Combination therapy with donepezil plus memantine is the evidence-based approach for patients who continue to decline on cholinesterase inhibitor monotherapy, as explicitly recommended by consensus guidelines 2
The FDA label for memantine demonstrates statistically significant improvement in cognition and function when added to donepezil in patients with moderate to severe Alzheimer's disease who had been on stable donepezil therapy for at least 6 months 3
At 24 weeks, combination therapy showed a mean difference of 1.6 units on the ADCS-ADL scale and 3.3 units on the SIB cognitive scale compared to donepezil monotherapy 3
Why Not Switch Medications
Switching from donepezil to rivastigmine (Option D) is not supported by evidence - while patients who don't respond to one cholinesterase inhibitor may respond to another, the clinical scenario describes only 3 months of treatment, which is insufficient to assess true treatment failure 1, 2
An assessment period of 6-12 months is necessary to properly evaluate treatment benefit before considering discontinuation or switching 1, 2
At only 3 months, this patient has not had adequate time to demonstrate response, making a switch premature 1
Why Not Switch to Memantine Alone
Switching donepezil to memantine monotherapy (Option C) would eliminate the cholinergic enhancement that may still be providing benefit, even if not clinically apparent at 3 months 1
The evidence strongly supports combination therapy rather than memantine monotherapy for patients already on cholinesterase inhibitors 2, 3
Why Not Add Sertraline
Adding sertraline (Option A) addresses depression or behavioral symptoms, not the core cognitive decline in Alzheimer's disease 1
Psychotropic agents should only be considered when behavioral disturbances persist despite cholinesterase inhibitor therapy and nonpharmacologic interventions 1
There is no indication in this clinical scenario that behavioral problems or mood disorders are the primary concern
Practical Implementation
Start memantine at 5 mg once daily and increase by 5 mg weekly in divided doses to reach the target dose of 20 mg/day (10 mg twice daily) 2, 3
Continue donepezil at its current dose while adding memantine 3
Reassess after 6-12 months of combination therapy to determine if there is stabilization or slower deterioration, which would constitute treatment success 1, 2
Important Caveats
The cortical atrophy on MRI is consistent with Alzheimer's disease but does not change the treatment approach 1
Three months is too short to declare treatment failure - most patients require 6-12 months to demonstrate benefit, using physician global assessment, caregiver reports, and neuropsychological testing 1, 2
Realistic expectations should emphasize that treatment aims to slow decline rather than reverse it 2
Answer: B. Add memantine