In an inpatient with confirmed mild‑to‑moderate Alzheimer‑type dementia and no contraindications (e.g., severe bradycardia, conduction block, uncontrolled asthma/COPD, recent gastrointestinal bleeding, hepatic impairment, or hypersensitivity), should we start donepezil now instead of waiting for discharge?

Should Donepezil Be Started in the Inpatient Setting?

Yes, initiate donepezil 5 mg once daily now in the inpatient setting for confirmed mild-to-moderate Alzheimer's disease when reversible causes have been excluded and no contraindications exist. 1, 2

Rationale for Inpatient Initiation

Delaying symptomatic therapy until discharge is not necessary when the diagnosis is established and acute reversible contributors have been ruled out. The primary barriers to starting donepezil—excluding delirium, acute stroke, major depression, and other reversible causes—can be assessed during hospitalization. 1

Key Pre-Treatment Requirements Already Met

• Confirmed Alzheimer's diagnosis with mild-to-moderate severity (typically MMSE 10-26 or MoCA ≈16/30) 1, 3
• Exclusion of reversible causes: delirium from infection/metabolic disturbance, major depression, anticholinergic medication effects 1
• Absence of contraindications: no severe bradycardia, conduction block, uncontrolled asthma/COPD, recent GI bleeding, hepatic impairment, or hypersensitivity 2

Why Not Wait for Discharge?

Structural neuroimaging (CT/MRI) is recommended but not an absolute prerequisite for starting symptomatic therapy; its purpose is to detect treatable structural lesions (subdural hematoma, tumor, normal-pressure hydrocephalus), not to confirm Alzheimer's pathology. 1 If imaging has not been completed, order it promptly but do not delay donepezil initiation when reversible causes are clinically excluded. 1

Practical Implementation Algorithm

Step 1: Confirm Eligibility (Inpatient Assessment)

• Document cognitive impairment severity with validated tool (MMSE, MoCA, or ADAS-Cog) 1
• Screen for major depression (can mimic dementia) 1
• Review cardiac history for sick-sinus syndrome or significant bradycardia 1
• Assess active GI conditions (peptic ulcer, severe GERD) that cholinergic effects may worsen 1
• Check anticoagulation status; if present, expedite brain imaging before starting therapy 1

Step 2: Initiate Therapy Before Discharge

• Start donepezil 5 mg once daily in the evening, just prior to bedtime 2
• Administer with food to minimize gastrointestinal side effects (nausea, vomiting, diarrhea) 4, 1
• No laboratory monitoring required (donepezil is not hepatotoxic) 4, 1

Step 3: Counsel Patient and Caregiver

• Set realistic expectations: donepezil provides modest benefit—approximately 20-35% of patients achieve clinically meaningful improvement equivalent to delaying decline by one year, representing a 5-15% benefit over placebo 5, 3
• Explain that treatment stabilizes or slows decline rather than reversing dementia 1, 5
• Warn about transient GI symptoms (nausea, vomiting, diarrhea) that typically resolve within a few weeks 4, 3
• Mention possible initial increase in agitation that usually subsides after the first few weeks 1, 3

Step 4: Arrange Outpatient Follow-Up

• Titration visit at 4-6 weeks: increase to 10 mg daily if 5 mg is well tolerated; the higher dose provides greater cognitive and functional benefit but carries 2.5-3.2-fold higher risk of GI side effects 1, 2
• Full efficacy assessment at 6-12 months using physician global impression, caregiver reports of functional/behavioral changes, and comprehensive cognitive testing (brief tools like MMSE are relatively insensitive to drug effects) 4, 1

Safety Profile Supporting Inpatient Start

Donepezil has no serious adverse event risk beyond expected cholinergic effects. High-quality systematic reviews show no statistically significant difference between donepezil and placebo for serious adverse events. 1

• Common side effects: mild, transient GI symptoms (nausea, vomiting, diarrhea) that are dose-related and reduced by taking with food 5, 3
• No hepatotoxicity (unlike tacrine) 4, 5
• Withdrawal rates: 5-20% due to adverse events, comparable to placebo rates of 7-13% 1
• Cardiac effects: potential vagotonic effects on sinoatrial/atrioventricular nodes may manifest as bradycardia or heart block, but this is manageable with appropriate screening 2

Common Pitfalls to Avoid

• Do not delay initiation awaiting outpatient neurology consultation when diagnosis is established and contraindications are absent 1
• Do not wait for brain imaging if reversible structural causes have been clinically excluded; order imaging but proceed with therapy 1
• Do not start at 10 mg; always begin at 5 mg and titrate after 4-6 weeks 2
• Do not rely solely on MMSE for response assessment; use caregiver reports and functional measures 4, 1
• Do not discontinue prematurely; a full 6-12 month trial is required to assess benefit 4, 1

Expected Outcomes

Approximately 20-35% of patients will show a 7-point improvement on neuropsychologic tests (equivalent to one year's decline), while others may experience stabilization rather than continued worsening. 5, 3 Beneficial effects on cognition typically become apparent by week 3 of treatment. 6 Global function improvements (assessed by CIBIC-plus) are consistently maintained throughout 24-week study durations. 3