In a 72-year-old man with Lewy-body dementia on escitalopram, quetiapine, and donepezil who is isolated for an upper respiratory tract infection and now has persistent hiccups, what is the appropriate work‑up and treatment?

Hiccups in a 72-Year-Old with Lewy Body Dementia on Donepezil

Donepezil is the most likely culprit for this patient's hiccups and should be dose-reduced or discontinued immediately, as this medication is a well-documented cause of intractable hiccups in dementia patients. 1

Immediate Work-Up

Medication Review (Priority Assessment)

• Donepezil is directly implicated in causing intractable hiccups through its cholinergic mechanism, with documented cases showing hiccup resolution upon dose reduction or discontinuation 1
• The FDA label confirms cholinergic excess from donepezil overdosage includes salivation, sweating, and other parasympathetic symptoms that can manifest as hiccups 2
• Consider that donepezil may have limited benefit in advanced dementia and carries significant adverse effects including nausea, vomiting, diarrhea, and bradyarrhythmias 3

Rule Out Serious Causes

• Check for metabolic derangements: electrolyte abnormalities (particularly hyponatremia from escitalopram), uremia, hypocalcemia 4
• Assess for gastric distension or gastroesophageal irritation related to the URTI (swallowed air, post-nasal drip) 1
• Evaluate for central nervous system involvement: worsening of underlying Lewy body pathology, though less likely if hiccups are the only new symptom 1
• Basic labs: Complete metabolic panel, particularly focusing on sodium and renal function 4

Treatment Algorithm

Step 1: Medication Adjustment (First-Line)

• Reduce donepezil dose by 50% immediately (e.g., from 10mg to 5mg) or hold for 24-48 hours to assess response 1
• If hiccups resolve with dose reduction, consider whether continued donepezil is warranted given:
  • Lack of long-term benefit in advanced dementia 3
  • Patient's current symptom burden 3
  • The cholinesterase inhibitor may be safely tapered off, especially when there is perceived lack of benefit 3

Step 2: Symptomatic Management (If Hiccups Persist After Donepezil Adjustment)

• Avoid chlorpromazine despite its traditional use for hiccups, as it carries severe risks in this population:

  • Rapid-onset agranulocytosis (can occur within days) 4
  • Worsens cognitive function in dementia 3
  • High anticholinergic burden contraindicated in Lewy body dementia 3
  • FDA black box warning for increased mortality in dementia patients 3

• Consider safer alternatives:

  • Baclofen 5-10mg three times daily (GABA-B agonist, less sedating)
  • Metoclopramide 10mg three times daily (use cautiously given extrapyramidal side effect risk in Lewy body dementia)
  • Gabapentin 300mg three times daily (if renal function permits)

Step 3: Non-Pharmacological Interventions

• Vagal maneuvers: Valsalva, drinking cold water, breath-holding techniques 1
• Address URTI symptoms: Adequate hydration, treatment of post-nasal drip to reduce gastric irritation 1

Critical Medication Safety Considerations

Polypharmacy Review in This Patient

• Quetiapine carries significant risks in Lewy body dementia including cognitive worsening, falls, stroke, and death 3
• The combination of escitalopram, quetiapine, and donepezil increases anticholinergic burden and fall risk 3
• Consider deprescribing quetiapine if behavioral symptoms are controlled, as atypical antipsychotics should be avoided when possible in dementia 3

Specific to Lewy Body Dementia

• Donepezil has level-1 evidence for cognitive symptoms and hallucinations in DLB, but benefits must be weighed against adverse effects 5, 6
• If psychosis is the primary indication for quetiapine and it persists, consider pimavanserin as a safer alternative with better tolerability in DLB 7

Common Pitfalls to Avoid

• Do not reflexively prescribe chlorpromazine for hiccups in elderly dementia patients—the risks far outweigh benefits 4, 3
• Do not continue donepezil at full dose while adding additional medications for hiccups when the donepezil itself is likely causative 1
• Do not overlook the opportunity to deprescribe medications with questionable benefit in advanced dementia 3
• Remember that typical and atypical antipsychotics worsen outcomes in Lewy body dementia and should be minimized 3, 7