What are the recommended medications for an elderly patient with dementia?

Recommended Medications for Elderly Patients with Dementia

Cholinesterase inhibitors (donepezil, galantamine, or rivastigmine) should be prescribed as first-line treatment for patients with mild to moderate Alzheimer's disease, with donepezil offering the most straightforward dosing and best tolerability profile. 1, 2

First-Line Pharmacological Treatment

Cholinesterase Inhibitors

For mild to moderate Alzheimer's disease, initiate treatment with one of three cholinesterase inhibitors: 1

• Donepezil: Start at 5 mg once daily, may increase to 10 mg daily after 4-6 weeks 2. This produces a statistically significant improvement of approximately 2.7 points on the ADAS-Cog scale, though the clinical benefit is modest 1. Donepezil has the advantage of once-daily dosing and straightforward titration 3.

• Galantamine: Start at 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, may increase to 12 mg twice daily based on tolerability 2, 4. Maximum dose is 16-24 mg daily 5. Galantamine produces approximately 2 points improvement on ADAS-Cog 1.

• Rivastigmine: Initiate at 1.5 mg twice daily, increase by 1.5 mg twice daily every 4 weeks as tolerated, with maximum dose of 6 mg twice daily 2. Food intake reduces adverse effects 6.

All three agents show comparable efficacy, with improvements in cognition, global function, activities of daily living, and behavior, though effect sizes are small. 1, 3

Moderate to Severe Alzheimer's Disease

Memantine (alone or combined with a cholinesterase inhibitor) is recommended for moderate to severe disease: 2, 7

• Start at 5 mg once daily, increase weekly by 5 mg/day in divided doses to 20 mg/day (10 mg twice daily) 7
• Combination therapy with memantine plus donepezil provides cumulative, additive benefits over monotherapy 2, 7
• At 24 weeks, combination therapy showed 3.3 points improvement on SIB and 1.6 units on ADCS-ADL compared to donepezil alone 7

Adjunctive Therapy

Vitamin E (1,000 IU orally twice daily) should be considered to attempt slowing AD progression, as it has a more favorable risk-benefit ratio than other putative disease-modifying agents. 1

Management of Behavioral Symptoms

When environmental interventions fail, antipsychotics should be used to treat agitation or psychosis: 1

• Atypical agents (risperidone, olanzapine, quetiapine) are better tolerated than traditional agents like haloperidol 1
• Cholinesterase inhibitors may reduce behavioral disturbances and should not be discontinued during active psychotic symptoms, agitation, or aggression 1, 2

For depression in dementia, consider selective serotonin reuptake inhibitors, tricyclics, or monoamine oxidase-B inhibitors, with side-effect profiles guiding agent choice. 1

Comparative Effectiveness

Direct comparisons show no significant differences in efficacy between cholinesterase inhibitors, though donepezil appears better tolerated than rivastigmine: 1, 3

• Donepezil causes fewer adverse events than rivastigmine 3
• Network meta-analysis ranks donepezil 10 mg first for cognitive benefit, though it ranks third for adverse events 5
• Galantamine ranks second for both benefit and harm 5

Adverse Effects and Tolerability

Approximately 29% of patients discontinue cholinesterase inhibitors due to adverse events versus 18% on placebo: 3

• Common adverse effects include nausea, vomiting, diarrhea, dizziness, and abdominal pain 1, 6, 5
• Donepezil 5 mg shows little difference from placebo in adverse events (OR 1.22), while donepezil 10 mg shows slight excess (OR 1.95) 5
• Galantamine 16-24 mg is associated with slight excess adverse events (OR 1.57) 5
• Slow titration over more than three months reduces cholinergic adverse effects 6, 3

Medications to Avoid

Estrogen should not be prescribed to treat Alzheimer's disease. 1

Avoid medications with anticholinergic side effects that worsen cognitive symptoms. 2

When to Discontinue Treatment

Deprescribe cholinesterase inhibitors or memantine when: 1

• No clinically meaningful benefit observed at any time during treatment 1
• Severe or end-stage dementia with dependence in most basic ADLs 1
• Development of intolerable side effects (confusion, dizziness, falls) 1
• Poor medication adherence precludes safe use 1

Discontinue gradually: reduce dose by 50% every 4 weeks until reaching initial starting dose, then discontinue after 4 weeks. 1

Reinitiate treatment if clinically meaningful worsening of cognition, function, or neuropsychiatric symptoms occurs after cessation. 1

Critical Caveats

• These medications provide symptomatic treatment only and do not alter underlying disease progression; patients continue to decline despite treatment 1, 2
• The average cognitive improvement (2-3 points on ADAS-Cog) represents statistically significant but clinically marginal benefit 1
• Most trial data are limited to 6-month duration, restricting ability to detect long-term effects 1
• Evidence is strongest for mild to moderate Alzheimer's disease; limited data exist for severe dementia or other dementia types 1
• For vascular dementia, donepezil 10 mg and galantamine 16-24 mg probably improve cognition slightly, though clinical importance is uncertain 5