Treatment of Persistent Hiccups
For persistent hiccups, initiate treatment with baclofen or gabapentin as first-line pharmacological therapy, while simultaneously addressing any underlying conditions such as GERD with proton pump inhibitors. 1, 2
Initial Assessment and Underlying Cause Management
When evaluating a patient with persistent hiccups (lasting >48 hours), the priority is identifying and treating reversible underlying conditions:
If GERD is suspected as the underlying cause, start a proton pump inhibitor (PPI) such as omeprazole 20 mg once daily taken before meals as first-line therapy. 1, 3 The American Gastroenterological Association recommends this approach for hiccups potentially related to gastroesophageal reflux. 1
For inadequate response to standard PPI dosing, escalate to twice-daily dosing (before breakfast and dinner) to optimize acid suppression. 4, 1 This is particularly important for extraesophageal manifestations of GERD. 1
Add lifestyle modifications including elevation of the head of bed by 6-8 inches and avoiding lying down for 2-3 hours after meals. 5, 1 These measures reduce esophageal acid exposure and may help control hiccup triggers. 5
Pharmacological Treatment Algorithm
First-Line Agents
Baclofen and gabapentin should be considered as first-line pharmacological therapy for persistent and intractable hiccups based on the best available evidence. 2
Baclofen is the drug of choice for centrally-mediated hiccups, acting as a GABA-B agonist on the hiccup reflex arc. 2, 6 It is supported by small randomized, placebo-controlled trials and is less likely to cause side effects during long-term therapy compared to neuroleptic agents. 2
Gabapentin is an effective alternative agent acting on the hiccup reflex arc, with observational data supporting its efficacy. 2, 7 It has a favorable side effect profile for long-term use. 2
Second-Line Agents
If first-line therapy fails or is not tolerated:
Metoclopramide is recommended as first choice for peripherally-mediated hiccups, supported by small randomized, placebo-controlled trials. 2, 6 However, the American Gastroenterological Association advises against its use as monotherapy for GERD-related symptoms due to unfavorable risk-benefit profile, including tardive dyskinesia risk. 1
Chlorpromazine has observational data supporting efficacy and is widely employed for intractable hiccups. 2, 8, 7 However, it carries higher risk of side effects during long-term therapy compared to baclofen or gabapentin. 2
Adjunctive Therapy for GERD-Related Hiccups
If hiatal hernia is present or breakthrough symptoms occur:
Consider adding alginate antacids for breakthrough symptoms, particularly if hiatal hernia is documented. 1 These provide a physical barrier to reflux. 1
Baclofen may be effective for belch-predominant symptoms and mild regurgitation, though it is limited by CNS and GI side effects. 9, 1
Non-Pharmacological Approaches
Before or alongside pharmacological therapy:
Simple physical maneuvers such as breath holding, stimulating the uvula or pharynx, or disrupting diaphragmatic rhythm may terminate acute hiccup episodes. 8, 6 These are simple to use and often effective for self-limited hiccups. 8
For refractory cases, interventional procedures such as vagal or phrenic nerve block or stimulation should be considered in patients who do not respond to medications. 6
Treatment Duration and Response Assessment
Allow 2 weeks to several months to assess response to anti-reflux therapy, as the timeline for GERD-related symptom improvement is more variable than for other conditions. 4 Some patients respond to high-dose PPI therapy within 2 weeks, while others may take several months. 4
For extraesophageal manifestations like hiccups, implement twice-daily PPI dosing for a minimum of 8-12 weeks before concluding treatment failure. 1
Common Pitfalls and Caveats
Do not use metoclopramide as monotherapy for GERD-related hiccups due to the risk of tardive dyskinesia and unfavorable risk-benefit profile. 1 Reserve it for cases where peripheral mechanisms are clearly identified. 6
Avoid assuming all persistent hiccups are benign—they can indicate serious underlying pathology including stroke, space-occupying lesions, myocardial ischemia, or malignancy along the reflex arc. 7 Central causes require different pharmacological approaches than peripheral causes. 6
Do not discontinue PPI therapy prematurely in suspected GERD-related hiccups, as response may take several months and require addition of prokinetic therapy. 4
Recognize that no high-quality randomized controlled trials exist for hiccup treatment, so recommendations are based on limited efficacy and safety data from small studies and observational reports. 2