What is the recommended dose of chlorpromazine (CPZ) for treating intractable hiccups?

Chlorpromazine Dosing for Intractable Hiccups

For intractable hiccups, chlorpromazine should be administered at 25-50 mg orally three to four times daily, and if symptoms persist for 2-3 days, parenteral therapy is indicated. 1

FDA-Approved Dosing Regimen

The FDA label provides the only official dosing guidance for chlorpromazine in hiccups:

• Oral dosing: 25-50 mg three to four times daily (TID or QID) 1
• Duration before escalation: If symptoms persist for 2-3 days on oral therapy, switch to parenteral (intramuscular or intravenous) administration 1
• Maximum consideration: While not explicitly stated for hiccups, the FDA label notes that daily dosages up to 800 mg are not uncommon in other conditions, though therapeutic gain beyond 1,000 mg daily is limited 1

Clinical Evidence Supporting This Approach

Chlorpromazine remains the only FDA-approved medication specifically indicated for hiccup treatment 2, though the evidence base is limited:

• Recent case reports demonstrate successful resolution of persistent hiccups with chlorpromazine 25 mg every 8 hours, with complete symptom resolution after 4 doses in one COVID-19-associated case 3
• Another case showed improvement within 10 hours using chlorpromazine for COVID-19-related persistent hiccups 4

Important Safety Considerations and Monitoring

Chlorpromazine carries significant risks that must be monitored closely:

• Extrapyramidal symptoms: Dyskinesia can occur even at doses as low as 75 mg/day after 4 weeks of treatment 5
• Cardiovascular effects: Hypotension and QT interval prolongation are well-documented, particularly with repeated doses 6
• Sedation: Somnolence is common and may impair function 5
• Elderly patients: Require lower doses and closer observation due to increased susceptibility to hypotension and neuromuscular reactions 1

Alternative Agents When Chlorpromazine Fails or Is Not Tolerated

If chlorpromazine causes intolerable side effects or proves ineffective after 2-3 days:

• Baclofen and metoclopramide are the only agents studied in randomized controlled trials for hiccups 2
• Gabapentin has prospective evidence supporting its use 2
• Risperidone may be superior to haloperidol in some cases, with complete hiccup abolition within 6 hours in one report, possibly due to its serotonergic properties 7
• Haloperidol at 0.05-0.15 mg/kg IM/IV can be used, though it carries similar risks of dystonic reactions and QT prolongation 6

Common Pitfalls to Avoid

• Underdosing: Starting below 25 mg TID may be ineffective; use the FDA-recommended range from the outset 1
• Prolonged oral therapy without escalation: If no improvement after 2-3 days, switch to parenteral route rather than continuing ineffective oral dosing 1
• Ignoring adverse effects: Dyskinesia and hypotension can develop rapidly; monitor closely and discontinue if these occur 5
• Using in elderly without dose adjustment: Always start at lower end of dosing range and titrate gradually in older patients 1