What medication changes are recommended for a patient with dementia requiring a medication adjustment?

Medication Changes for Dementia Patients

For patients with dementia requiring medication adjustment, prioritize non-pharmacological interventions first, then initiate cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for mild-to-moderate Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, or vascular dementia, starting at the lowest dose and titrating slowly. 1

Initial Assessment Before Medication Changes

Before adjusting any dementia medications, document the following:

• Current cognitive status using validated scales (MMSE for screening with >80% sensitivity/specificity, or MoCA for better detection of mild cognitive impairment and mild Alzheimer's disease) 1
• Functional abilities in activities of daily living to establish baseline 1
• Neuropsychiatric symptoms including agitation, psychosis, depression, or behavioral disturbances 1, 2
• Dementia subtype (Alzheimer's disease, vascular dementia, Lewy body dementia, Parkinson's disease dementia, frontotemporal dementia) as this determines appropriate medication selection 1
• Current medication list to identify potential drug interactions, anticholinergic burden, and medications that may worsen cognition 3, 4

Initiating Cognitive Enhancers

For Alzheimer's Disease, Vascular Dementia, Parkinson's Disease Dementia, or Dementia with Lewy Bodies:

Mild-to-Moderate Dementia:

• First-line: Donepezil starting at 5 mg daily, increasing to 10 mg daily after 4-6 weeks 1
• Alternatives: Rivastigmine or galantamine with similar efficacy profiles 1
• These medications show statistically significant but modest cognitive benefits (average ADAS-cog improvement not reaching the 4-point clinically meaningful threshold, though subsets of patients do achieve meaningful improvement) 1

Moderate-to-Severe Dementia:

• Add memantine (starting 5 mg daily, titrating to 10 mg twice daily) to cholinesterase inhibitor therapy 1
• Combination therapy (memantine plus donepezil) is recommended for moderate-to-severe Alzheimer's disease 1

Parkinson's Disease Dementia Specifically:

• Rivastigmine is FDA-approved and preferred for symptomatic treatment 5

For Frontotemporal Dementia or Other Non-Alzheimer Dementias:

• Do not initiate cholinesterase inhibitors or memantine as they are not indicated and should be discontinued if already prescribed 1

Managing Behavioral and Psychological Symptoms

Non-Pharmacological Interventions (First-Line):

These must be attempted before antipsychotics:

• Environmental modifications: structured activities, supervision, environmental safety measures 1, 2
• Caregiver education and support regarding reassurance techniques and behavioral management 1, 2
• Identify and treat underlying causes: pain, delirium, infections, constipation, medication side effects 2

Pharmacological Management of Agitation/Psychosis:

When non-pharmacological interventions fail and symptoms are severe, dangerous, or cause significant distress:

• For agitated dementia WITH delusions: Antipsychotic monotherapy is first-line 2, 6

  • Risperidone 0.5-2.0 mg/day (first-line) 6
  • Quetiapine 50-150 mg/day (high second-line) 6
  • Olanzapine 5.0-7.5 mg/day (high second-line) 6

• For agitated dementia WITHOUT delusions: Antipsychotic alone is high second-line (60% of experts rated first-line), but consider cholinesterase inhibitor optimization first 2, 6

Critical Safety Considerations:

• Conduct risk-benefit discussion documenting increased mortality risk, stroke risk, falls, and cognitive decline before initiating antipsychotics 2
• Start at lowest possible dose and titrate slowly 2
• Monitor response quantitatively after 4 weeks 2
• Discontinue if no response after 4 weeks at adequate dose 2
• Attempt discontinuation within 3-6 months even if effective, as symptoms may stabilize 2

Drug-Specific Considerations for Antipsychotics:

Avoid or use extreme caution:

• Quetiapine: Increased exposure with CYP3A4 inhibitors (reduce dose to 1/6 with ketoconazole); avoid alcohol and centrally-acting drugs 3
• Risperidone: Adjust dose with CYP2D6 inhibitors (fluoxetine, paroxetine increase exposure 1.4-1.8x); do not exceed 8 mg/day with these combinations 4
• Clozapine and olanzapine: Avoid in patients with diabetes, dyslipidemia, or obesity 6
• Quetiapine is first-line for Parkinson's disease patients due to lower extrapyramidal side effects 6

Depression Management:

For agitated non-psychotic major depression:

• Antidepressant monotherapy is first-line (77% expert consensus) 6
• SSRI selection: Prefer sertraline or citalopram over fluoxetine/paroxetine due to fewer drug interactions and less anticholinergic effects 1, 4
• Avoid adding antipsychotics unless psychotic features present 6

For psychotic depression:

• Antidepressant PLUS antipsychotic is first-line (98% expert consensus) 6
• ECT is also first-line (71% expert consensus) 6

Deprescribing Considerations

When to Consider Discontinuing Cognitive Enhancers:

Discontinue cholinesterase inhibitors or memantine if: 1

• Clinically meaningful worsening over past 6 months despite treatment (in absence of delirium or acute illness)
• No observed benefit at any time during treatment (no improvement, stabilization, or decreased decline rate)
• Severe or end-stage dementia with dependence in most basic ADLs or limited life expectancy
• Intolerable side effects (severe nausea, vomiting, weight loss for ChEIs; confusion, dizziness, falls for memantine)
• Poor medication adherence precluding safe use
• Wrong indication: Prescribed for frontotemporal dementia or other non-indicated conditions

Exception: Do NOT discontinue cholinesterase inhibitors if:

• Active psychotic symptoms, agitation, or aggression are present and unstable (unless symptoms worsened after ChEI initiation) 1
• Meaningful reduction in neuropsychiatric symptoms occurred with the cognitive enhancer, even if cognitive/functional decline continues 1

Deprescribing Protocol:

• Reduce dose by 50% every 4 weeks until reaching initial starting dose 1
• After 4 weeks at starting dose, discontinue completely 1
• Reinitiate treatment if clinically meaningful worsening of cognition, function, neuropsychiatric symptoms, or global assessment occurs after cessation 1

Monitoring After Medication Changes

Reassess at 4 weeks:

• Cognitive function using same validated scale as baseline 1, 2
• Functional abilities in ADLs 1
• Neuropsychiatric symptoms with quantitative measures 2
• Side effects particularly gastrointestinal (ChEIs), dizziness/confusion (memantine), or extrapyramidal symptoms (antipsychotics) 1, 3, 4

Ongoing monitoring:

• Periodic reassessment every 3-6 months to determine lowest effective maintenance dose 1, 6
• Annual comprehensive medication review to identify polypharmacy issues and deprescribing opportunities 7, 8