Baclofen for Intractable Hiccups
Baclofen is an effective treatment for intractable hiccups and should be considered as first-line pharmacological therapy, with typical dosing of 5-10 mg three times daily, titrated up to 20 mg three times daily as needed. 1, 2
Evidence Supporting Baclofen Use
Baclofen is one of only two medications studied in randomized controlled trials for intractable hiccups, demonstrating consistent efficacy:
- A double-blind, randomized, placebo-controlled crossover study showed statistically significant improvement in hiccup severity (p = 0.03) and hiccup-free periods (p = 0.003) with baclofen treatment. 3
- A systematic review of 341 patients across 15 studies identified baclofen and metoclopramide as the only agents supported by small randomized, placebo-controlled trials, with baclofen recommended as first-line therapy alongside gabapentin due to better long-term safety profiles compared to neuroleptic agents. 2
- Multiple case reports demonstrate successful resolution of intractable hiccups with baclofen monotherapy, including a patient with 5-year duration hiccups responding to a single oral dose. 4
Mechanism of Action
Baclofen functions as a GABA-B receptor agonist that reduces the mechanical aspects of hiccup by activating inhibitory neurotransmitters, which blocks the hiccup stimulus at the reflex arc level within the spinal cord. 5, 3
Practical Dosing Approach
- 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. 6
- Gradually titrate upward to 10-20 mg three times daily based on response and tolerability. 1
- Administer doses with meals to reduce gastrointestinal side effects, and consider timing the largest dose before sleep to allow peak sedative effects to occur during rest. 7
Critical Safety Considerations
Avoid baclofen 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. 8, 9
Additional high-risk populations requiring caution:
- Dementia patients should avoid baclofen due to cognitive and safety concerns. 6, 9
- Patients with compromised respiratory function (COPD, asthma) require careful monitoring. 9
- Eliminate or minimize concomitant CNS depressants (opioids, benzodiazepines, alcohol) due to additive sedative effects. 6, 7
Withdrawal Risk Management
Never discontinue baclofen abruptly—always taper gradually to avoid potentially life-threatening withdrawal syndrome. 7
Withdrawal symptoms include:
- Visual and auditory hallucinations, anxiety, agitation, delirium 7
- Fever, tremors, tachycardia, seizures 7
- In severe cases: rhabdomyolysis, multiorgan failure, and death 7
Alternative and Combination Therapy
If baclofen monotherapy fails:
- Gabapentin represents an alternative first-line option with similar efficacy and favorable safety profile. 1, 2
- Metoclopramide has randomized trial support but carries risk of extrapyramidal side effects with long-term use. 1, 2
- Chlorpromazine is FDA-approved for hiccups but causes more side effects than baclofen or gabapentin during prolonged therapy. 8, 1, 2
- Combination therapy with baclofen plus low-dose olanzapine has shown success in treatment-refractory cases. 5
When Baclofen Is Not Appropriate
The 2017 CHEST guidelines mention baclofen only as an experimental approach for opioid-resistant cough in lung cancer patients, noting it should be considered in N-of-1 trials when standard treatments fail—this context differs from hiccup management. 8
For intractable hiccups specifically, baclofen remains the best-studied and most appropriate first-line pharmacological option, provided respiratory contraindications are absent. 1, 2, 3