What is the recommended dose of Donepezil (Aricept) for treating organic delirium?

Donepezil for Organic Delirium

Donepezil is not recommended for the treatment of organic delirium as there is insufficient evidence supporting its efficacy for this indication. Instead, antipsychotics remain the first-line pharmacological treatment for delirium when medication is necessary 1.

Current Evidence and Recommendations

• Antipsychotics, particularly haloperidol, are the first-line pharmacological treatment for delirium when medications are needed. The recommended starting dose for haloperidol is 0.5-1 mg PO or SC, with PRN dosing of 0.5-1 mg every hour as needed 1.
• For elderly or frail patients, lower doses of haloperidol (0.25-0.5 mg) should be used initially and titrated gradually 1.
• Second-generation antipsychotics like olanzapine (2.5-5 mg), quetiapine (25 mg), or risperidone (0.5 mg) may be alternatives with potentially fewer extrapyramidal side effects 1.
• Benzodiazepines should be reserved primarily for alcohol or benzodiazepine withdrawal delirium, or as crisis medication for severe agitation and distress 1.

Why Not Donepezil?

• There is limited research evidence for cholinesterase inhibitors like donepezil in the treatment of delirium 2.
• A Cochrane systematic review found no significant difference between donepezil and placebo in the duration of postoperative delirium 2.
• While cholinergic dysfunction has been proposed as a mechanism in delirium, clinical evidence does not support routine use of donepezil for this indication 3.
• Isolated case reports have suggested potential benefit in specific cases of delirium with basal forebrain lesions 4 or delirium complicating dementia 5, but these findings have not been validated in controlled trials.

Management Approach for Delirium

1. Non-pharmacological interventions should be first-line:

   • Identify and treat underlying causes 1
   • Optimize environmental factors (proper lighting, orientation cues) 1
   • Ensure adequate hydration 1

2. When pharmacological treatment is necessary:

   • Use antipsychotics at the lowest effective dose for the shortest duration possible 1
   • Haloperidol starting at 0.5-1 mg (0.25-0.5 mg in elderly) 1
   • Second-generation alternatives: olanzapine, quetiapine, or risperidone 1

3. Monitoring:

   • Regular assessment using standardized tools like CAM-ICU or ICDSC 1
   • Monitor for extrapyramidal symptoms, QTc prolongation, and other side effects 1

Important Caveats

• No medication is currently licensed worldwide specifically for delirium management 1.
• Antipsychotics and benzodiazepines can themselves cause increased agitation and delirium 1.
• Medications should be used for the shortest period possible and primarily when the patient has perceptual disturbances or poses a risk to themselves or others 1.
• Deprescribing medications that may contribute to delirium is an important strategy 1.

In conclusion, while donepezil is indicated for Alzheimer's disease at doses of 5-10 mg daily 1, it is not recommended for the treatment of organic delirium based on current evidence.