What medications are used to treat hiccups?

Medications for Hiccups

For intractable hiccups, chlorpromazine 25-50 mg orally three to four times daily remains the only FDA-approved treatment, though baclofen (5-10 mg three times daily) and gabapentin are increasingly preferred alternatives due to better tolerability, particularly in rehabilitation and elderly populations. 1, 2

First-Line Pharmacologic Options

Chlorpromazine (FDA-Approved)

• Chlorpromazine is the only FDA-approved medication specifically indicated for intractable hiccups, with a recommended dose of 25-50 mg orally three to four times daily. 1
• If symptoms persist for 2-3 days on oral therapy, parenteral administration may be indicated. 1
• Major limitation: significant sedation and risk of extrapyramidal symptoms (EPS), particularly problematic in rehabilitation settings where patient participation is critical. 3, 2
• Monitor closely for hypotension and neuromuscular reactions, especially in elderly patients who are more susceptible to these adverse effects. 1
• QT prolongation is a significant concern that requires monitoring. 2

Baclofen (Preferred Alternative)

• Baclofen 5-10 mg three times daily is recommended as an effective alternative with superior tolerability compared to chlorpromazine. 2
• Baclofen and metoclopramide are the only agents studied in randomized controlled trials for hiccup treatment. 4
• Works through GABA-B receptor agonism, modulating the hiccup reflex arc at the central level. 4, 5

Gabapentin (Emerging Preferred Option)

• Gabapentin has demonstrated effectiveness in multiple case series, particularly in stroke rehabilitation patients where sedation from chlorpromazine would impair participation. 3, 6
• Dosing ranges from 100 mg three times daily to 400 mg twice daily, with therapeutic response typically seen within 2 days to 5.5 weeks. 6
• Gabapentin offers favorable tolerability at modest doses, though worsened confusion has been reported in one case. 6
• Particularly useful when chlorpromazine fails or is contraindicated. 3

Second-Line Options

Metoclopramide

• Metoclopramide 10-20 mg orally or IV every 4-6 hours is effective for persistent hiccups. 2, 7
• One of only two agents (along with baclofen) studied in randomized controlled trials. 4
• Monitor for dystonic reactions; diphenhydramine can be used for treatment, or benztropine in patients allergic to diphenhydramine. 7, 8

Haloperidol

• Haloperidol 0.5-2 mg orally or IV every 4-6 hours can be used as an alternative antipsychotic with antiemetic and anti-hiccup properties. 2, 7
• Lower doses minimize risk of extrapyramidal symptoms while maintaining efficacy. 2

Adjunctive Medications

Benzodiazepines

• Lorazepam 0.5-2 mg every 4-6 hours (oral, sublingual, or IV) may be helpful, especially when anxiety is a contributing factor. 2, 7
• Works through GABA-A receptor agonism, providing rapid onset with no active metabolites. 8
• Monitor for CNS depression, respiratory depression, and paradoxical aggression in older adults. 8

Treatment Algorithm

1. Initial approach: Start with baclofen 5-10 mg three times daily OR gabapentin 100 mg three times daily, particularly in rehabilitation patients or elderly where sedation is problematic. 2, 6

2. If baclofen/gabapentin unavailable or ineffective: Use chlorpromazine 25-50 mg three to four times daily, with close monitoring for sedation and EPS. 1, 2

3. For breakthrough or refractory cases: Add metoclopramide 10-20 mg every 4-6 hours OR haloperidol 0.5-2 mg every 4-6 hours. 2, 7

4. If anxiety component present: Add lorazepam 0.5-2 mg every 4-6 hours to primary regimen. 2

5. If EPS develop: Administer diphenhydramine or benztropine for dystonic reactions. 7, 8

Critical Pitfalls to Avoid

• Overlooking drug-induced hiccups: Some medications cause hiccups and require discontinuation of the offending agent rather than adding more medications. 2
• Underestimating sedation in rehabilitation patients: Chlorpromazine's sedating effects can significantly impair participation in physical therapy and delay recovery. 3
• Not monitoring for EPS with dopamine antagonists: Both chlorpromazine and metoclopramide carry significant risk of extrapyramidal symptoms requiring prophylaxis or treatment. 2, 8
• Avoiding prochlorperazine in liver disease: Increased risk of extrapyramidal symptoms in hepatic impairment. 2
• Failing to adjust doses in elderly patients: Lower doses are generally sufficient and reduce adverse effect risk. 1

Special Populations

Elderly patients: Use lower initial doses of all agents, increase dosage more gradually, and observe closely for hypotension and neuromuscular reactions. 1

Rehabilitation patients: Strongly favor gabapentin or baclofen over chlorpromazine to avoid sedation that impairs therapy participation. 3, 6

Patients with liver disease: Avoid prochlorperazine; use alternative agents with caution and dose adjustment. 2