Why Gabapentin is Used for Chronic Cough
Gabapentin is prescribed for unexplained chronic cough because it targets the underlying neurogenic mechanism of cough hypersensitivity—a condition where the cough reflex pathways become abnormally sensitized, similar to neuropathic pain syndromes. 1, 2
The Neurogenic Basis of Chronic Cough
Chronic refractory cough represents a form of cough hypersensitivity syndrome where sensory nerve dysfunction causes patients to cough in response to normally innocuous stimuli (low-level physical triggers like talking, laughing, or temperature changes). 3 This mechanism parallels central sensitization seen in neuropathic pain conditions, where peripheral and central augmentation of afferent pathways creates hypersensitivity. 3
Key features supporting the neuropathic diagnosis include:
- Sensory symptoms suggesting upper airway and laryngeal neural dysfunction 3
- Triggered cough from minimal stimuli that wouldn't normally provoke coughing 3
- Vocal fold motion asymmetry on laryngoscopy in 80% of patients, suggesting vagal neuropathy 4
Evidence for Gabapentin's Efficacy
The 2016 CHEST guidelines recommend gabapentin as a therapeutic trial for unexplained chronic cough based on a landmark randomized controlled trial. 1
The pivotal Ryan et al. study demonstrated:
- Significant improvement in cough-specific quality of life (Leicester Cough Questionnaire score difference of 1.80 points, p=0.004) 2
- Reduction in objective cough frequency 1
- Number needed to treat of only 3.58 2
- 64-66% therapeutic success rate in subsequent studies 4, 5
Clinical Application and Dosing
The CHEST Expert Panel recommends the following approach: 1
Dosing protocol:
- Start at 300 mg once daily 1
- Add additional doses each day as tolerated 1
- Titrate up to maximum tolerable dose of 1,800 mg daily in two divided doses 1
Critical requirements before prescribing:
- Discuss potential side effects and risk-benefit profile with patients 1
- Reassess the risk-benefit profile at 6 months before continuing 1
- Ensure the patient has undergone guideline-based assessment excluding treatable causes (asthma, GERD, post-nasal drip, eosinophilic bronchitis) 1
Side Effect Profile
Common adverse effects occur in approximately 31% of patients and include: 1
- Confusion, dizziness, dry mouth 1
- Fatigue and nausea 1
- Less commonly: blurred vision, headache, memory loss 1
Important consideration: Side effects can be managed through dose modification, and adverse event rates were not significantly different from placebo in the pivotal trial. 1 However, these effects may limit the maximum tolerable dose in some patients. 1
Predictors of Response
Patients most likely to respond to gabapentin: 4, 5
- Those with vocal fold motion asymmetry on videostroboscopy (94% response rate vs. 56% without) 4
- Hull Airway Reflux Questionnaire (HARQ) scores >21.50 (sensitivity 84.6%, specificity 63.6%) 5
- Specific symptoms including throat tickle/lump sensation, morning cough, and cough with eating 5
Position in Treatment Algorithm
Gabapentin should be considered: 1
- After objective testing for bronchial hyperresponsiveness and eosinophilic bronchitis has been negative 1
- Alongside or after multimodality speech pathology therapy 1
- Before considering opiates, which are reserved for refractory cases when all alternatives have failed 1
The American Thoracic Society identifies gabapentin as the first-line neuromodulator for unexplained chronic cough. 6 For interstitial lung disease-associated refractory cough, gabapentin is also recommended as a first-line option following the same protocols. 7
Common Pitfalls to Avoid
- Do not prescribe gabapentin without first completing a thorough evaluation to exclude treatable causes of chronic cough 1
- Do not use inhaled corticosteroids if testing for bronchial hyperresponsiveness and eosinophilia is negative 1
- Do not prescribe proton pump inhibitors empirically if GERD workup is negative 1
- Do not continue gabapentin indefinitely without reassessing at 6 months 1