What are the best medications for treating intractable hiccups?

Best Medications for Intractable Hiccups

Chlorpromazine is the only FDA-approved medication for intractable hiccups and should be the first-line pharmacologic treatment, dosed at 25-50 mg orally three to four times daily, or 25-50 mg intramuscularly if oral therapy fails after 2-3 days. 1, 2

First-Line Treatment: Chlorpromazine

• Chlorpromazine remains the gold standard as it is the sole FDA-approved agent specifically indicated for intractable hiccups 1, 2, 3
• Oral dosing: Start with 25-50 mg three to four times daily 1
• Parenteral route: If symptoms persist for 2-3 days on oral therapy, administer 25-50 mg intramuscularly 2
• For refractory cases: Use slow IV infusion with patient flat in bed: 25-50 mg in 500-1000 mL saline, monitoring blood pressure closely 2
• Mechanism: Acts as a dopamine receptor antagonist, likely interrupting the hiccup reflex arc at the medullary level 4, 3

Important Caveats with Chlorpromazine

• Monitor for dystonic reactions, orthostatic hypotension, and QTc prolongation 4
• Chlorpromazine may not be optimal in rehabilitation or elderly patients due to sedation, hypotension, and extrapyramidal side effects 5
• Avoid in patients with multiple QT-prolonging medications or cardiac risk factors 4

Second-Line Alternatives When Chlorpromazine Fails or Is Contraindicated

Gabapentin (Preferred Alternative)

• Gabapentin has demonstrated effectiveness in case series and may be better tolerated than chlorpromazine, particularly in rehabilitation settings 5
• Dosing: Titrate up to 1800 mg/day in divided doses 3, 5
• Advantages: Fewer extrapyramidal side effects compared to antipsychotics 5
• Caution: Can cause somnolence at higher doses 6

Baclofen

• Baclofen is supported by randomized controlled trial evidence for persistent hiccups 3, 7
• Dosing: Start low and titrate up to 50 mg/day in divided doses 3
• Mechanism: GABA-B agonist that may suppress the hiccup reflex arc 7
• Caution: Can cause severe somnolence and hypotension; requires gradual titration 6

Metoclopramide

• Metoclopramide has randomized controlled trial evidence and dual benefit as both prokinetic and dopamine antagonist 3, 7
• Dosing: 10-20 mg orally or IV every 4-6 hours 4
• Particularly useful when gastroparesis or gastric outlet obstruction contributes to hiccups 4
• Monitor for dystonic reactions; have diphenhydramine available 4

Haloperidol

• Haloperidol is an alternative dopamine antagonist used in palliative care settings 4
• Dosing: 0.5-2 mg orally or IV every 4-6 hours 4
• Advantages: Less sedating than chlorpromazine in some patients 3
• Caution: Still carries risk of extrapyramidal symptoms and QTc prolongation 4, 6

Algorithm for Treatment Selection

1. Start with chlorpromazine 25-50 mg PO TID-QID unless contraindications exist (elderly, cardiac risk factors, rehabilitation patients) 1, 2

2. If chlorpromazine fails after 2-3 days orally, switch to IM route (25-50 mg) 2

3. If chlorpromazine is not tolerated or contraindicated:

   • For rehabilitation/elderly patients: Try gabapentin (titrate to 1800 mg/day) 5
   • For patients with gastroparesis: Try metoclopramide (10-20 mg QID) 4, 3
   • For palliative care patients: Try haloperidol (0.5-2 mg q4-6h) or baclofen (up to 50 mg/day) 4, 3

4. For truly refractory cases after single-agent failure:

   • Consider combination therapy with agents from different classes 3
   • Consider tetrabenazine in post-stroke hiccups unresponsive to typical antipsychotics 6
   • Consider nebulized lidocaine as last resort (5 mL of 0.2% TID), though assess aspiration risk first 4

Critical Monitoring Points

• All antipsychotic agents require cardiac monitoring for QTc prolongation, especially with concurrent medications that prolong QT interval 4
• Watch for extrapyramidal symptoms with all dopamine antagonists; treat with diphenhydramine 25-50 mg if dystonia occurs 4
• Assess for underlying causes requiring specific treatment: GERD, CNS lesions (especially brainstem/medullary), metabolic abnormalities, gastric distension 4, 7
• In post-stroke patients with intractable hiccups, consider that supratentorial lesions may disrupt dopaminergic modulation of medullary hiccup centers 6