What is the treatment approach for patients with chronic hiccups?

Treatment of Chronic Hiccups

For patients with chronic hiccups (lasting >48 hours), initiate empiric treatment with a proton pump inhibitor (PPI) as first-line therapy, since gastroesophageal reflux disease (GERD) is the most common identifiable cause, and if symptoms persist after 2-3 weeks, add chlorpromazine 25-50 mg three to four times daily as the FDA-approved pharmacologic agent with the strongest evidence base. 1, 2

Initial Assessment and Diagnostic Approach

• Determine hiccup duration: Persistent hiccups last >48 hours, while intractable hiccups persist >2 months 3
• Identify medication triggers: Review for anti-parkinsonism drugs, anesthetic agents, steroids, and chemotherapy agents that can cause hiccups 3
• Assess for serious underlying pathology: Look specifically for myocardial infarction, stroke, brain tumors, renal failure, abdominal malignancies, and recent surgical procedures 4
• Obtain focused gastrointestinal history: Ask about heartburn, regurgitation, dysphagia, and epigastric pain, as gastric/duodenal ulcers, gastritis, and esophageal reflux are commonly observed 4

Treatment Algorithm

Step 1: Empiric GERD Treatment (First-Line)

• Start PPI therapy immediately as GERD is the most common identifiable cause of chronic hiccups 2
• Add dietary modifications: Eliminate foods with >45 g fat per day, coffee, tea, soda, chocolate, mints, citrus products (including tomatoes), and alcohol 5
• Implement lifestyle changes: Advise no smoking and limiting vigorous exercise that increases intra-abdominal pressure 5
• Assess response within 1-3 months before proceeding to next step 5

Step 2: Add Pharmacologic Therapy if PPI Fails

• Chlorpromazine 25-50 mg three to four times daily is the FDA-approved treatment for intractable hiccups and the most widely employed agent 1, 6, 4

  • For severe cases, may increase gradually to 200 mg daily or higher if needed 1
  • Monitor for hypotension and neuromuscular reactions, especially in elderly patients 1
  • If symptoms persist for 2-3 days on oral therapy, consider parenteral administration 1

• Alternative pharmacologic options if chlorpromazine is contraindicated or ineffective:

  • Baclofen has emerged as a safe and often effective treatment 4
  • Gabapentin may be considered 3
  • Metoclopramide (prokinetic agent) can be added to PPI therapy 6, 4

Step 3: Intensify GERD Treatment if Partial Response

• Add prokinetic therapy (metoclopramide) to PPI if not already prescribed 5
• Consider switching from H2-antagonist to PPI if patient was on H2-blocker, as proton pump inhibition may be effective when H2-antagonism has failed 5
• Mitigate comorbid conditions: Address obstructive sleep apnea and discontinue medications that worsen reflux (nitrates, progesterone, calcium channel blockers) whenever possible 5

Step 4: Comprehensive Diagnostic Evaluation for Refractory Cases

• Upper gastrointestinal investigations: Perform endoscopy, 24-hour pH monitoring, and esophageal manometry systematically, as these should be included in diagnostic evaluation for all chronic hiccup patients 4
• Imaging studies based on clinical suspicion:
  • Chest CT scan if respiratory symptoms present 4
  • Brain CT scan if neurologic signs present 4
  • Abdominal ultrasound if abdominal pathology suspected 4

Step 5: Advanced Interventions for Intractable Cases

• Consider antireflux surgery if:

  • 24-hour esophageal pH monitoring before treatment was positive 5
  • Patient fits clinical profile suggesting GERD as likely cause 5
  • Cough has not improved after minimum 3 months of intensive medical therapy 5
  • Serial pH monitoring shows medical therapy has failed to control reflux 5
  • Patient reports unsatisfactory quality of life 5

• Non-pharmacologic interventions: Nerve blockade (phrenic nerve), pacing, acupuncture, and hypnosis have been used in severe cases 3, 6

Common Pitfalls to Avoid

• Do not assume GERD is ruled out if empiric PPI therapy fails: The therapy may not have been intensive enough, requiring addition of prokinetic agents and stricter dietary modifications 5
• Do not overlook central nervous system causes: Stroke, space-occupying lesions, and brain injury can cause hiccups through disruption of the central midbrain modulation 3
• Do not delay chlorpromazine in severely symptomatic patients: This is the only FDA-approved medication specifically for intractable hiccups and should be started early if hiccups are causing depression, weight loss, or sleep deprivation 1, 4
• Do not forget to check for peripheral nerve irritation: Lesions along the phrenic, vagal, and sympathetic pathways (tumors, herpes infection, myocardial ischemia) can trigger the hiccup reflex arc 3