Best Drug for Intractable Cough
For intractable dry cough, dextromethorphan is the preferred first-line treatment due to its superior efficacy and better side effect profile compared to codeine and other opioids, with maximum cough suppression occurring at 60 mg doses. 1
First-Line Treatment Approach
- Dextromethorphan at 60 mg provides maximum cough reflex suppression with prolonged effect, which is substantially higher than typical over-the-counter preparations (usually 10-30 mg). 1
- Simple adjunctive measures including honey and lemon mixtures, adequate hydration, and menthol inhalation can provide symptomatic relief and should be initiated alongside pharmacologic therapy. 1
- First-generation sedating antihistamines are particularly useful when nocturnal cough disrupts sleep. 1
Second-Line Treatment: Gabapentin
If dextromethorphan fails, gabapentin is the evidence-based second-line agent for refractory chronic cough. 1, 2
Gabapentin Dosing Protocol
- Start at 300 mg once daily and titrate upward to a maximum tolerable dose of 1,800 mg daily in two divided doses. 2
- A landmark randomized controlled trial demonstrated significant improvement in cough-specific quality of life (Leicester Cough Questionnaire score improvement of 1.80 points, p=0.004) with a number needed to treat of 3.58. 3
- Common adverse effects occur in approximately 31% of patients and include confusion, dizziness, dry mouth, fatigue, and nausea. 2
- Reassess efficacy at 6 months and do not continue indefinitely without reevaluation. 2
Comparative Evidence
- Gabapentin and baclofen have similar therapeutic efficacy (57.3% vs 53.0% success rates), but gabapentin causes significantly less somnolence (20.5% vs 35.0%) and dizziness (11.1% vs 23.9%) than baclofen, making it the preferred neuromodulator. 4
Third-Line Treatment: Multimodality Speech Pathology
- For patients who fail pharmacologic therapy, multimodality speech pathology therapy including cough suppression techniques, vocal hygiene, and psychoeducational counseling has demonstrated efficacy in decreasing objective cough frequency and improving quality of life. 5, 1
Refractory Cough: Opioid Therapy
When all alternative treatments have failed and cough severely impacts quality of life, low-dose opioids should be considered, particularly in palliative settings. 5, 1
Opioid Implementation
- Slow-release morphine 5 mg twice daily has shown significant improvement in quality of life (mean LCQ score increase of 3.2 points) in a positive randomized controlled trial. 5
- Alternative opioids include hydrocodone and dihydrocodeine, starting at low doses and titrating to effect. 1
- For lung cancer patients with opioid-resistant cough, peripherally acting antitussives like levodropropizine may be considered. 1
- Mandatory reassessment of benefits and risks at 1 week, then monthly before continuing opioid therapy. 5, 1
- Most common side effects are constipation and drowsiness, though generally well tolerated. 5
Important Caveat
The CHEST guidelines note that opiates narrowly failed the 80% voting threshold for unexplained cough recommendations, yet the expert panel consensus supports their use when cough substantially impacts quality of life and all alternatives have failed. 5
Special Considerations for GERD-Related Cough
- If gastroesophageal reflux disease contributes to cough, implement intensive treatment including antireflux diet, proton pump inhibitors, and prokinetic therapy before escalating to neuromodulators or opioids. 1
- In one study, patients whose GERD resolved showed clinically significant LCQ score improvement (from 14.3 to 17.9), while those with persistent GERD had unchanged scores. 5
Treatment Algorithm Summary
- Start with dextromethorphan 60 mg (higher than OTC doses)
- Add gabapentin 300 mg daily, titrate to 1,800 mg if dextromethorphan fails
- Consider multimodality speech pathology for persistent symptoms
- Reserve opioids (morphine 5 mg twice daily) for refractory cases with severe quality of life impairment, with mandatory monthly reassessment