Is Thorazine (chlorpromazine) effective for treating hiccups?

Chlorpromazine for Hiccups

Chlorpromazine is the only FDA-approved medication for treating hiccups and should be considered the first-line pharmacologic agent for persistent or intractable hiccups, despite limited high-quality evidence and significant side effects that require careful monitoring. 1, 2

Evidence Base and Regulatory Status

• Chlorpromazine remains the sole drug with FDA approval specifically for hiccup treatment, giving it unique regulatory standing among all pharmacologic options 1
• The evidence supporting chlorpromazine consists primarily of anecdotal reports and clinical experience rather than controlled trials, reflecting the overall poor quality of hiccup treatment literature 3
• In clinical practice, chlorpromazine was used as first-choice treatment in 96% (23/24) of hospitalized patients with persistent hiccups in one case series, though 30% required second-line agents 4

Mechanism and Clinical Application

• Chlorpromazine functions as a central nervous system dopamine receptor antagonist, which is believed to suppress the hiccup reflex arc 5, 3
• As a "low-potency" typical antipsychotic, it produces more sedation but fewer extrapyramidal symptoms compared to high-potency agents like haloperidol 5
• The drug also has anticholinergic, antihistaminic, and alpha-adrenergic receptor activity, contributing to both therapeutic effects and side effects 5

Dosing Considerations

While specific dosing protocols for hiccups are not detailed in the guidelines reviewed, chlorpromazine for other indications typically requires:

• Careful titration based on patient response
• Lower doses in elderly patients due to increased sensitivity
• Monitoring for dose-related adverse effects 5

Critical Safety Concerns

Cardiovascular monitoring is mandatory when using chlorpromazine due to several serious risks:

• QTc prolongation with potential for torsades de pointes arrhythmia, requiring baseline and follow-up ECG monitoring 6, 5
• Hypotension occurs more frequently with chlorpromazine than other antipsychotics, particularly orthostatic hypotension 6, 5
• Avoid co-administration with other QT-prolonging medications (including common drugs like ondansetron, azithromycin, ciprofloxacin, and diphenhydramine) 6, 5

Neurological side effects include:

• Extrapyramidal symptoms (though less common than with high-potency antipsychotics) 6, 5
• Neuroleptic malignant syndrome (rare but potentially fatal) 6
• Paradoxical agitation, particularly in elderly patients 6

Other significant adverse effects:

• Respiratory depression when combined with other CNS depressants 6
• Anticholinergic effects (dry mouth, urinary retention, confusion) 6
• Sedation that may persist for hours to days 6

Alternative Pharmacologic Options

When chlorpromazine is contraindicated or ineffective, consider:

Baclofen and metoclopramide are the only agents studied in randomized controlled trials for hiccups 1

• These represent the strongest alternative evidence base, though still limited
• Baclofen is frequently used in clinical practice with favorable reported outcomes 2

Gabapentin has been studied prospectively and may be considered 1

Haloperidol (another dopamine antagonist) is commonly used for chronic hiccups, though paradoxically one case report describes perphenazine (a related antipsychotic) causing hiccups 7

Clinical Decision Algorithm

1. Assess underlying etiology: Most persistent hiccups (88% in one series) have identifiable organic causes, particularly digestive tract disorders and CNS diseases 4

   • Look specifically for advanced malignancies, especially GI tumors
   • Review medication list for hiccup-inducing drugs (corticosteroids and benzodiazepines most common) 4

2. Evaluate cardiac risk before initiating chlorpromazine:

   • Obtain baseline ECG to assess QTc interval 6, 5
   • Review all concurrent medications for QT-prolonging agents 6
   • Assess for electrolyte abnormalities (hypokalemia, hypomagnesemia) 6
   • Consider cardiology consultation if baseline QTc >450 ms or multiple risk factors present 5

3. Initiate chlorpromazine if cardiac risk acceptable:

   • Start with low doses and titrate based on response
   • Implement continuous monitoring for hospitalized patients 6
   • Reassess if QTc exceeds 500 ms 6

4. Switch to alternative agent if:

   • Chlorpromazine fails after adequate trial (occurred in 30% of cases) 4
   • Unacceptable side effects develop
   • Cardiac contraindications exist
   • Consider baclofen or metoclopramide as second-line options 1, 2

Prognostic Considerations

• Persistent hiccups requiring hospitalization often indicate serious underlying disease with poor prognosis 4
• In one series, 50% of patients died during follow-up, with 61% of deaths occurring within 3 months 4
• Average hospital stay for persistent hiccups was 13 days (range 3-90 days), indicating significant morbidity 4

Common Pitfalls to Avoid

• Do not assume hiccups are benign: Persistent cases warrant thorough evaluation for serious underlying pathology, particularly malignancy 4
• Do not overlook drug-induced hiccups: Review and discontinue potential causative medications (especially corticosteroids and benzodiazepines) before adding chlorpromazine 4
• Do not combine multiple QT-prolonging agents: This dramatically increases arrhythmia risk 6, 5
• Do not use promethazine for extrapyramidal symptoms if they develop: Despite being a phenothiazine, promethazine causes rather than treats EPS 8
• Do not neglect monitoring in elderly patients: They are at higher risk for hypotension, paradoxical agitation, and cardiac complications 6