Is baclofen indicated for intractable cough?

Is Baclofen Indicated for Intractable Cough?

Baclofen is not routinely indicated for intractable cough due to lack of high-quality evidence from double-blind placebo-controlled trials, though it may be considered as a later-line option in highly refractory cases after standard therapies have failed, particularly for gastroesophageal reflux-induced chronic cough. 1

Evidence Quality and Limitations

The evidence supporting baclofen for intractable cough is weak and consists primarily of:

• No double-blind placebo-controlled trials exist for baclofen in pathologic cough, despite animal studies and open-label human data showing potential benefit 1
• Case reports and small open-label studies showing suppression of ACE inhibitor-induced cough and chronic refractory cough 1, 2
• One systematic review identified baclofen among neuromodulators studied for chronic idiopathic cough, but noted significant methodologic limitations 1

Mechanism and Theoretical Rationale

Baclofen acts as a GABA-B receptor agonist with both central and spinal mechanisms:

• Spinal action on the efferent limb of the cough reflex, potentially reducing intense expiratory efforts during repetitive coughing 1
• Demonstrated antitussive activity in animal models and suppression of capsaicin-induced cough in humans 1
• May reduce cough hypersensitivity in gastroesophageal reflux-related cough 1, 3

Clinical Trial Data

Comparative Effectiveness

• A 2019 randomized trial (n=217 completers) compared gabapentin versus baclofen for suspected refractory GERD-induced chronic cough 3
• Similar efficacy: Success rates were comparable (gabapentin 57.3% vs baclofen 53.0%, p=0.550) 3
• Inferior tolerability: Baclofen caused significantly more somnolence (35.0% vs 20.5%, p=0.013) and dizziness (23.9% vs 11.1%, p=0.010) compared to gabapentin 3

Other Studies

• Small studies (n=12-16 patients) showed 53-56% response rates in refractory GERD-induced cough when added to proton pump inhibitors 4, 5
• Improvements in cough sensitivity to capsaicin and symptom scores observed 4, 3

Side Effect Profile

Baclofen has a challenging side effect profile that limits its clinical utility: 1

• Common adverse effects include somnolence, dizziness, and fatigue 4, 3
• May inhibit swallowing function through central mechanisms 6
• Abrupt discontinuation must be avoided due to potential withdrawal symptoms 6
• Requires dose adjustment in renal impairment 6

Guideline Recommendations and Expert Consensus

For Lung Cancer-Related Intractable Cough

• The 2017 CHEST guideline suggests baclofen may be considered using N-of-1 randomized controlled trials when surgery, chemotherapy, radiation, and standard therapies have failed 1
• This is an ungraded consensus-based statement reflecting the lack of definitive evidence 1

For Unexplained Chronic Cough

• The 2016 CHEST guideline on unexplained chronic cough does not include baclofen in formal recommendations 1
• Gabapentin received a formal recommendation (Grade 2C) over baclofen for unexplained chronic cough 1

For GERD-Related Symptoms

• The 2023 AGA clinical practice update notes baclofen is not routinely recommended as primary or adjunctive therapy for extraesophageal reflux symptoms due to its challenging side effect profile 1

Clinical Algorithm for Use

If considering baclofen for intractable cough, follow this approach:

1. Exclude and treat all identifiable causes of chronic cough first (asthma, GERD, postnasal drip, ACE inhibitors, etc.) 1

2. Try first-line neuromodulators first:

   • Gabapentin (up to 1800 mg/day) is preferred due to better tolerability and formal guideline support 1, 3
   • Consider speech pathology interventions for cough hypersensitivity 1

3. Consider baclofen only if:

   • Gabapentin has failed or is not tolerated 3
   • GERD-related refractory cough is suspected despite adequate acid suppression 4, 3
   • Patient can tolerate CNS side effects and has normal renal function 6

4. Dosing approach:

   • Start low (5-10 mg three times daily) and titrate to maximum 20 mg three times daily 1, 4
   • Assess response after 2 weeks, with maximum benefit potentially at 6-8 weeks 4
   • Monitor closely for somnolence, dizziness, and fatigue 4, 3

5. For lung cancer patients with intractable cough:

   • Consider N-of-1 trial design with randomization, blinding, and patient-important outcomes 1

Key Clinical Pitfalls

• Do not use baclofen as first-line therapy for any type of chronic cough given lack of robust evidence and inferior tolerability compared to gabapentin 1, 3
• Avoid in elderly patients or those with renal impairment without dose adjustment due to increased CNS effects 6
• Never stop abruptly after prolonged use due to withdrawal risk 6
• Do not expect universal response: Even in selected populations, only 50-60% of patients respond 4, 3