What is the strongest antitussive (cough suppressant) medication?

Strongest Antitussive Medication

Morphine is the strongest antitussive available, reserved for refractory cough unresponsive to other opioid derivatives, though for most clinical situations, hydrocodone or dihydrocodeine represent the most effective first-line opioid options. 1

Hierarchy of Antitussive Strength

Most Potent Agents (Opioids)

Morphine stands as the ultimate cough suppressant when other measures fail:

• Reserved for cough not suppressed by other opioid derivatives or centrally acting agents like dextromethorphan 1
• Starting dose: 5 mg single-dose trial; if effective, use 5-10 mg slow-release morphine twice daily 1
• For patients already on morphine for other symptoms, increasing the dose by 20% may help suppress cough 1

Hydrocodone and Dihydrocodeine are the most widely used and effective opioids for routine cough suppression:

• Hydrocodone: 5 mg twice daily, with median effective dose of 10 mg/day achieving 70% reduction in cough frequency 1
• Dihydrocodeine: 10 mg three times daily 1
• These agents are preferred over codeine due to superior efficacy-to-side-effect ratio 1

Other potent opioids include:

• Pholcodine: 10 mL four times daily (where available) 1
• Methadone linctus: 2 mg single dose 1
• Diamorphine: 5-10 mg subcutaneously over 24 hours 1
• Hydromorphone (case reports support efficacy) 1

Why Codeine Is NOT the Strongest Despite Being Most Studied

Codeine is explicitly less preferred despite extensive research:

• Greater side effect profile (drowsiness, nausea, constipation, physical dependence) compared to other opioids 1, 2, 3
• No greater efficacy than dextromethorphan 2, 3, 4
• Objective studies show codeine is no more effective than placebo in COPD patients 5 and acute upper respiratory infections 6
• Standard dose: 30-60 mg four times daily 1

Non-Opioid Central Agents

Dextromethorphan is the strongest non-opioid option:

• Maximum cough reflex suppression occurs at 60 mg (not the typical over-the-counter 15-30 mg doses) 2, 3
• Superior safety profile compared to opioids 2, 3, 4
• Dose range: 10-15 mg three to four times daily, up to maximum 120 mg/day 1
• Standard OTC dosing is often subtherapeutic 2, 3

Peripheral Acting Agents

Levodropropizine shows comparable efficacy to dihydrocodeine:

• 75 mg three times daily 1
• Lower somnolence rate (8%) compared to dihydrocodeine (22%) 1
• Not available in the United States 1

Other peripheral agents:

• Moguisteine: 100-200 mg three times daily 1
• Benzonatate: 100-200 mg four times daily 1

Last-Resort Options for Intractable Cough

Nebulized local anesthetics for cough refractory to all other approaches:

• Nebulized lidocaine: 5 mL of 0.2% three times daily 1
• Nebulized bupivacaine: 5 mL of 0.25% three times daily 1
• Critical caveat: Assess aspiration risk before use, as local anesthetics increase aspiration risk in frail patients 1
• Avoid food and drink for at least 1 hour after administration 1

Clinical Algorithm for Selecting Strongest Appropriate Agent

1. For severe, refractory cough requiring maximum suppression:

   • Start with hydrocodone 5 mg twice daily or dihydrocodeine 10 mg three times daily 1
   • Titrate hydrocodone up to 30 mg/day if needed 1

2. If inadequate response to first-line opioids:

   • Escalate to morphine 5 mg trial dose; if effective, use 5-10 mg slow-release twice daily 1
   • Consider alternative opioids like pholcodine or methadone 1

3. For patients where opioids are contraindicated or refused:

   • Use dextromethorphan 60 mg for maximum effect 2, 3
   • Consider levodropropizine 75 mg three times daily if available 1

4. For absolutely intractable cough despite maximal opioid therapy:

   • Trial nebulized lidocaine 5 mL of 0.2% three times daily after confirming low aspiration risk 1

Important Caveats

Availability varies by country - choice may be dictated by local formulary rather than pharmacologic superiority 1

Patient's prior opioid exposure dictates initial starting dose - opioid-naive patients require lower doses 1

Avoid codeine as first-line despite its historical status as the "gold standard" - it has inferior benefit-to-risk ratio 1, 2, 3

Do not use antitussives for productive cough where secretion clearance is beneficial 2, 3