Chlorpromazine for Intractable Hiccups
For intractable hiccups, chlorpromazine 25-50 mg orally three to four times daily is the FDA-approved first-line pharmacologic treatment, with escalation to parenteral administration (25-50 mg IM or slow IV infusion) if oral therapy fails after 2-3 days. 1, 2
FDA-Approved Dosing Regimen
Oral therapy:
- Start with 25-50 mg three to four times daily (every 6-8 hours) 1
- This is the only FDA-approved medication specifically indicated for hiccups 3, 4
- Continue for 2-3 days to assess response 1
Parenteral therapy (if oral fails):
- Intramuscular: 25-50 mg IM, can repeat as needed 2
- Intravenous: 25-50 mg diluted in 500-1000 mL saline as slow infusion 2
- Patient must remain flat in bed with close blood pressure monitoring during IV administration 2
- IV route is reserved specifically for severe/intractable hiccups 2
Critical Safety Monitoring
Cardiovascular precautions are mandatory:
- Monitor for QTc prolongation, orthostatic hypotension, and sinus tachycardia 5
- Keep patient supine for at least 30 minutes after parenteral administration 2
- Avoid combining with other QT-prolonging medications without cardiac monitoring 5
Neurological side effects require vigilance:
- Watch for extrapyramidal symptoms (dystonic reactions, akathisia, pseudo-parkinsonism) 5, 6
- Have diphenhydramine 25-50 mg available to treat acute dystonic reactions 7
- These occur more frequently with chlorpromazine than atypical antipsychotics 5
Special Population Considerations
Elderly and debilitated patients need dose reduction:
- Start at 12.5-25 mg (lowest effective dose) 5, 1
- Increased fall risk from orthostatic hypotension and sedation 5
- Higher sensitivity to anticholinergic and extrapyramidal effects 5
Alternative Agents When Chlorpromazine Fails or Is Contraindicated
Second-line options with evidence from randomized controlled trials:
- Metoclopramide 10-40 mg PO/IV every 4-6 hours 7, 3
- Baclofen (studied in RCTs for persistent hiccups) 3
- Gabapentin (particularly useful in rehabilitation settings where chlorpromazine sedation is problematic) 3, 4
Third-line options for refractory cases:
- Haloperidol 0.5-2 mg PO/IV every 4-6 hours 7
- Monitor for extrapyramidal symptoms with both metoclopramide and haloperidol 7
Common Pitfalls to Avoid
Do not inject undiluted chlorpromazine directly into a vein - this can cause severe hypotension and tissue damage 2. Always dilute to at least 1 mg/mL for IV administration 2.
Avoid subcutaneous injection - use deep IM injection into upper outer quadrant of buttock only 2.
Do not use chlorpromazine as first-line antiemetic - it is specifically indicated for intractable hiccups, not routine nausea/vomiting where 5-HT3 antagonists are preferred 8.
Recognize that chlorpromazine may not be optimal in rehabilitation patients where sedation interferes with therapy participation - consider gabapentin as alternative 4.
Clinical Context
While chlorpromazine remains the only FDA-approved agent for hiccups 1, 3, the evidence base is limited. A systematic review found that baclofen and metoclopramide are the only agents studied in randomized controlled trials for this indication 3. However, FDA approval and decades of clinical experience support chlorpromazine as the initial pharmacologic choice when non-pharmacologic maneuvers fail 1, 9.
The mechanism involves dopamine receptor blockade in the brain's hiccup center 8, 9. Success rates vary, and some patients require alternative agents 4. Treatment selection should account for the patient's functional status, cardiovascular risk factors, and whether sedation will impair rehabilitation or daily activities 4.