What are the first-line and second-line medication treatments for hiccups in an adult patient with no significant medical history?

Medications for Hiccups

For an adult with no significant medical history experiencing hiccups, chlorpromazine 25-50 mg orally three to four times daily is the first-line pharmacologic treatment, as it remains the only FDA-approved medication for intractable hiccups. 1

First-Line Pharmacologic Treatment

Chlorpromazine should be initiated at 25-50 mg orally three to four times daily for persistent hiccups. 2, 1 This dopamine receptor antagonist likely interrupts the hiccup reflex arc at the medullary level. 2 If oral therapy fails after 2-3 days, escalate to 25-50 mg intramuscularly. 1, 3

Critical Monitoring with Chlorpromazine

• Monitor for orthostatic hypotension, particularly in the first 30 minutes after administration—patients should remain supine for at least 30 minutes following parenteral dosing. 2, 3
• Obtain baseline and follow-up ECGs to monitor for QTc prolongation, especially if the patient is on concurrent QT-prolonging medications. 2
• Watch for extrapyramidal symptoms (acute dystonia, drug-induced parkinsonism, akathisia) and have diphenhydramine 25-50 mg immediately available for treatment. 2, 4
• Elderly patients require lower starting doses due to increased susceptibility to hypotension and neuromuscular reactions. 1

Second-Line Pharmacologic Options

When chlorpromazine is contraindicated, ineffective, or poorly tolerated, consider these alternatives in the following order:

Metoclopramide (Preferred Second-Line)

Metoclopramide 10-20 mg orally or IV every 4-6 hours is particularly effective when gastroparesis or gastroesophageal reflux contributes to hiccups. 2, 5 This agent provides dual benefit as both a prokinetic and dopamine antagonist. 2

• Restrict use to ≤5 days optimally, with an absolute maximum of 12 weeks, to minimize risk of tardive dyskinesia. 5
• Maximum daily dose should not exceed 30 mg/day to reduce extrapyramidal risk. 5
• Contraindications include seizure disorders, GI bleeding, GI obstruction, and pheochromocytoma. 5
• Have diphenhydramine immediately available when initiating therapy. 5

Baclofen (Alternative Second-Line)

Baclofen 5-10 mg three times daily represents an effective alternative with a favorable safety profile. 4, 6 This GABA-B agonist has emerged as a safe option supported by randomized controlled trial evidence. 6, 7

Haloperidol (Palliative Care Setting)

Haloperidol 0.5-2 mg orally or IV every 4-6 hours can be used as an alternative dopamine antagonist, particularly in palliative care settings. 2, 4 Monitor for extrapyramidal symptoms and QTc prolongation. 2

Adjunctive Therapies

For GERD-Related Hiccups

Add proton pump inhibitors or H2-receptor antagonists when gastroesophageal reflux is suspected as the underlying trigger. 4, 8 GERD represents the most common identifiable cause of persistent hiccups. 8

For Anxiety-Related Hiccups

Consider benzodiazepines such as lorazepam 0.5-2 mg every 4-6 hours when anxiety contributes to the hiccup pattern. 4

Critical Treatment Principles

• Use scheduled around-the-clock dosing rather than PRN dosing for persistent hiccups to maintain therapeutic drug levels. 4
• Avoid concurrent use of multiple dopamine antagonists (chlorpromazine + metoclopramide + haloperidol) to prevent excessive dopamine blockade. 2
• Assess for underlying metabolic abnormalities (electrolyte disturbances) before initiating pharmacologic therapy, as correction may resolve hiccups. 2

Common Pitfalls to Avoid

• Do not continue metoclopramide as monotherapy beyond 5 days without reassessing the underlying cause and considering alternative agents. 5
• Do not ignore early extrapyramidal symptoms (restlessness, muscle stiffness, involuntary movements), as tardive dyskinesia can become irreversible. 5
• Do not underestimate sedation risk with chlorpromazine, especially in elderly patients who may require dose reduction. 4
• Do not overlook drug-induced hiccups—review the medication list and consider discontinuing potential offending agents. 4

Treatment Algorithm

1. Start with chlorpromazine 25-50 mg PO TID-QID 1
2. If ineffective after 2-3 days, switch to IM chlorpromazine 25-50 mg 1, 3
3. If chlorpromazine is contraindicated or fails, use metoclopramide 10-20 mg PO/IV Q4-6H (maximum 5 days) 2, 5
4. If both fail or are contraindicated, use baclofen 5-10 mg TID 4, 6
5. Consider adding PPI therapy regardless of chosen agent if GERD is suspected 4, 8
6. Have diphenhydramine and benztropine available for extrapyramidal symptom management 2, 4