Baclofen (Liofen) for Intractable Hiccups
Baclofen is a highly effective treatment for intractable hiccups and should be considered as a primary pharmacologic option, particularly when chlorpromazine is contraindicated or has failed. 1, 2
Evidence Supporting Baclofen Use
Baclofen has emerged as a safe and effective treatment for chronic hiccups, with substantial clinical evidence supporting its use:
A large case series of 37 patients with chronic hiccups (average duration 4.6 years) demonstrated that baclofen produced complete resolution in 18 patients and considerable improvement in 10 patients—a 76% success rate overall. 3
The American Geriatrics Society and other guideline bodies recognize baclofen as an established treatment option for intractable hiccups, though it is not FDA-approved for this indication (chlorpromazine remains the only FDA-approved agent). 1, 2
Baclofen works by acting as a GABA-B receptor agonist, likely interrupting the hiccup reflex arc at the central level. 4, 2
Practical Dosing Strategy
Start with 5 mg three times daily, particularly in elderly patients (≥65 years) who typically cannot tolerate doses greater than 30-40 mg per day. 1
Administer doses with meals to reduce gastrointestinal side effects. 1
Consider timing the largest dose before sleep to allow peak sedative effects to occur during rest. 1
In younger patients without contraindications, doses can be gradually titrated upward if needed, though most patients respond to lower doses. 3
Critical Safety Considerations and Contraindications
Baclofen must be avoided entirely in patients with obstructive sleep apnea, as it provokes upper airway collapse during sleep, worsens OSA, and can induce central apneas by depressing respiratory drive. 1
Additional high-risk populations requiring caution or avoidance:
Dementia patients should avoid baclofen due to cognitive and safety concerns. 1
Patients with compromised respiratory function (COPD, asthma) require careful monitoring. 1
Eliminate or minimize concomitant CNS depressants (opioids, benzodiazepines, alcohol) due to additive sedative effects. 1
Withdrawal Risk Management
Never discontinue baclofen abruptly—always taper gradually to avoid potentially life-threatening withdrawal syndrome characterized by seizures, hallucinations, and autonomic instability. 1
Treatment Algorithm Position
The treatment hierarchy for intractable hiccups based on current guidelines:
First-line: Chlorpromazine (25-50 mg orally three to four times daily, or 25-50 mg IM if oral fails after 2-3 days), but requires monitoring for dystonic reactions, orthostatic hypotension, and QTc prolongation. 5
Second-line alternatives when chlorpromazine fails or is contraindicated:
Third-line options:
Common Pitfalls to Avoid
Do not use baclofen in patients with renal impairment without dose adjustment, as it is renally cleared and accumulation can cause severe CNS toxicity. 1
Avoid combining multiple CNS depressants, as this dramatically increases sedation and respiratory depression risk. 1
Do not overlook underlying causes: Before initiating baclofen, evaluate for GERD, metabolic abnormalities, CNS lesions, and gastric distension, as treating the underlying cause may resolve hiccups. 5, 6
Chlorpromazine causes more side effects than baclofen or gabapentin during prolonged therapy, making baclofen preferable for long-term management despite chlorpromazine being FDA-approved. 1
Advantages of Baclofen Over Alternatives
Baclofen offers several advantages compared to chlorpromazine and other dopamine antagonists:
Lower risk of extrapyramidal symptoms and QTc prolongation compared to chlorpromazine, haloperidol, and metoclopramide. 5, 1
Better tolerability for long-term use, particularly important given that intractable hiccups often persist for months to years. 1, 3
Effective in both idiopathic cases and those with gastroesophageal disease, with no significant difference in response rates between these groups. 3