What are the most potent cough suppressants, including recommended doses, contraindications, and alternative options?

Most Potent Cough Suppressants

Opioids are the most potent cough suppressants available, with morphine sulfate (5-10 mg twice daily) demonstrating the strongest antitussive effect for intractable chronic cough, followed by hydrocodone and dihydrocodeine, while dextromethorphan 60 mg represents the most potent non-opioid option with a superior safety profile. 1, 2

Opioid Cough Suppressants (Most Potent)

Morphine Sulfate - Strongest Evidence

• Slow-release morphine sulfate 5-10 mg twice daily is the most effective antitussive for severe, treatment-resistant chronic cough, producing a 40% reduction in daily cough scores and 3.2-point improvement on validated cough questionnaires 2
• Reserved for the most severe chronic cough patients and those with terminal cancer who benefit from analgesic effects 3, 4
• Side effects include constipation and drowsiness, though tolerance develops with continued use 4, 2

Hydrocodone - Well-Studied Opioid

• Median effective dose of 10 mg/day (range 5-30 mg/day) achieved 70% reduction in cough frequency in patients with advanced cancer 1
• Administered as 5 mg twice daily with dose titration until 50% improvement in cough frequency 1
• Maximum daily dose of 120 mg, though most patients respond to lower doses 5

Dihydrocodeine

• Effective at 10 mg three times daily for 7 days in lung cancer patients 1
• Comparable antitussive efficacy to levodropropizine but with higher somnolence rate (22% vs 8%) 1
• Similar duration of cough suppression to non-opioid alternatives 1

Codeine - NOT Recommended Despite Being Opioid

• Codeine has no greater efficacy than dextromethorphan but significantly worse adverse effects including drowsiness, nausea, constipation, and physical dependence 5, 6
• Explicitly not recommended by multiple guidelines due to poor benefit-to-risk ratio 5, 6

Non-Opioid Cough Suppressants

Dextromethorphan - Most Potent Non-Opioid

• Maximum cough reflex suppression occurs at 60 mg single dose, which is higher than standard over-the-counter preparations (15-30 mg) 7, 5, 6
• Standard dosing: 10-15 mg three to four times daily, maximum 120 mg/day 5
• Bedtime dose of 15-30 mg helps suppress nocturnal cough 5
• Superior safety profile compared to all opioid alternatives with no risk of physical dependence 5, 6
• Critical pitfall: Standard OTC doses (30 mg or less) are subtherapeutic 7, 5

Peripherally Acting Antitussives

• Levodropropizine 75 mg three times daily shows comparable efficacy to dihydrocodeine with significantly less somnolence (8% vs 22%), but not available in United States 1
• Benzonatate is effective for opioid-resistant cough in lung cancer patients, offering different adverse effect profile 1, 5
• Moguisteine represents another peripherally acting option for refractory cases 5, 4

Ipratropium Bromide - Inhaled Option

• Only inhaled anticholinergic agent recommended for cough suppression in upper respiratory infections or chronic bronchitis 7
• Should be tried before central antitussives for postinfectious cough 7, 5, 6
• Level of evidence: fair; benefit: substantial; grade of recommendation: A 7

Dosing Algorithms by Clinical Scenario

For Severe/Intractable Chronic Cough

1. Start morphine sulfate 5 mg twice daily (slow-release formulation) 2
2. Assess response after 4 weeks 2
3. If inadequate response, escalate to 10 mg twice daily 2
4. Two-thirds of patients requiring dose escalation achieve similar improvement at 10 mg 2

For Moderate Chronic Cough or Lung Cancer

1. Start hydrocodone 5 mg twice daily 1
2. Titrate daily until 50% improvement in cough frequency 1
3. Median effective dose is 10 mg/day (range 5-30 mg/day) 1
4. If opioid-resistant, switch to benzonatate 1

For Acute Cough or When Avoiding Opioids

1. Dextromethorphan 60 mg for maximum suppression 7, 5
2. Alternative: 10-15 mg three to four times daily (every 6-8 hours) 5
3. Add 15-30 mg at bedtime for nocturnal cough 5
4. Caution: Check combination products for acetaminophen content to avoid hepatotoxicity at higher doses 5, 6

For Postinfectious Cough

1. Try ipratropium bromide first (inhaled) 7, 5, 6
2. If fails, add dextromethorphan 30-60 mg 7, 5
3. For severe paroxysms, consider prednisone 30-40 mg daily short course 7, 5

Critical Contraindications and Warnings

Opioid-Specific

• Risk of respiratory depression and hypoventilation - use graduated doses with caution 1
• Sedation, addiction potential, and constipation limit widespread utility 8, 9
• Reserved for severe cases where benefits outweigh risks 3, 4

Dextromethorphan-Specific

• Do not use when pneumonia assessment is needed 7
• Avoid in productive cough where secretion clearance is beneficial 7, 6
• Check for CYP2D6 drug interactions 6

General Contraindications

• Discontinue all antitussives if cough persists beyond 3 weeks - requires full diagnostic workup 7, 5
• Central cough suppressants have limited efficacy for URI-related cough 7, 6

Common Prescribing Pitfalls to Avoid

• Using subtherapeutic dextromethorphan doses (≤30 mg) when 60 mg provides optimal suppression 7, 5, 6
• Prescribing codeine-based products despite no efficacy advantage and worse side effects 7, 5, 6
• Continuing antitussive therapy beyond 3 weeks without diagnostic evaluation 7, 5
• Using central suppressants for productive cough 7, 6
• Overlooking acetaminophen content in dextromethorphan combination products 5, 6

Alternative and Adjunctive Options

First-Generation Antihistamines

• Suppress cough but cause drowsiness 7, 5
• Particularly useful for nocturnal cough due to sedative effects 7, 6
• Caution in elderly patients with dementia due to fall risk 6

Menthol Inhalation

• Provides acute but short-lived cough suppression 7, 5, 6
• Useful for quick temporary relief 7
• Can be prescribed as menthol crystals or proprietary capsules 5, 6

Corticosteroids

• High-dose corticosteroids may relieve cough from malignant airway involvement or treatment-induced pneumonitis 1
• Inhaled or nebulized steroids can be effective 1
• Prednisone 30-40 mg daily short course for severe postinfectious cough paroxysms 7, 5

Nebulized Lidocaine

• Last resort for refractory cases 5
• Limited evidence, primarily case reports 1