What is the strongest antitussive (cough suppressant)?

Strongest Antitussive

Morphine is the strongest antitussive available, achieving maximum cough suppression but reserved for refractory cases, while hydrocodone and dihydrocodeine represent the most effective first-line opioid options for routine severe cough suppression. 1

Hierarchy of Antitussive Potency

Most Potent: Morphine

• Morphine provides the greatest degree of cough suppression among all available antitussives but should be reserved exclusively for refractory cough unresponsive to other opioid derivatives 1
• Start with a 5 mg single-dose trial; if effective, use 5-10 mg slow-release morphine twice daily 1
• Slow-release morphine preparations have demonstrated efficacy in controlling intractable cough with acceptable tolerance to constipation and drowsiness 2
• This agent is particularly appropriate for terminal cancer patients who benefit from both antitussive and analgesic effects 3

First-Line Strong Opioids: Hydrocodone and Dihydrocodeine

• Hydrocodone and dihydrocodeine are the most widely used and effective opioids for routine cough suppression requiring maximum effect 1
• Hydrocodone: dose at 5 mg twice daily, titrating up to 30 mg/day if needed 1
• Dihydrocodeine: dose at 10 mg three times daily 1
• These agents demonstrate 40-60% suppression of cough counts in chronic bronchitis/COPD 4
• Levodropropizine shows comparable efficacy to dihydrocodeine for lung cancer-associated cough with significantly less somnolence 5

Strongest Non-Opioid: Dextromethorphan

• Dextromethorphan is the strongest non-opioid option, with maximum cough reflex suppression occurring at 60 mg 1
• Dose range: 10-15 mg three to four times daily, up to maximum 120 mg/day 1
• FDA-approved as a cough suppressant 6
• Achieves 40-60% cough suppression in chronic bronchitis/COPD, similar to codeine 4
• However, efficacy in upper respiratory infection-related cough is limited (<20% suppression), requiring larger patient populations to demonstrate significant effect 4

Clinical Algorithm for Selecting the Strongest Appropriate Agent

Step 1: Initial Selection for Severe Cough

• For severe, refractory cough requiring maximum suppression, start with hydrocodone 5 mg twice daily or dihydrocodeine 10 mg three times daily 1
• Adjust initial dose downward in opioid-naive patients 1
• Titrate hydrocodone up to 30 mg/day if inadequate response 1

Step 2: Escalation for Inadequate Response

• If first-line opioids fail, escalate to morphine 5 mg trial dose 1
• If the trial demonstrates efficacy, transition to 5-10 mg slow-release morphine twice daily 1

Step 3: Non-Opioid Alternative

• For patients where opioids are contraindicated or refused, use dextromethorphan 60 mg for maximum effect 1
• Alternative: levodropropizine 75 mg three times daily if available (not approved in the United States) 5, 1
• Levodropropizine achieves approximately 75% cough suppression in chronic or acute bronchitis with superior safety profile compared to opioids 4, 5

Critical Caveats

Codeine Should Be Avoided

• Codeine has an inferior benefit-to-risk ratio and should be avoided as first-line therapy despite its historical "gold standard" status 1
• While codeine demonstrates 40-60% suppression in chronic bronchitis 4, it is a prodrug requiring CYP2D6 bioactivation to morphine, creating unpredictable efficacy 7
• Codeine shows inconsistent efficacy in upper respiratory infection-related cough 4

Geographic Availability Limitations

• Medication availability varies significantly by country, and choice may be dictated by local formulary rather than pharmacologic superiority 1
• Levodropropizine and moguisteine are not approved in the United States 4, 5

Disease-Specific Efficacy Variations

• The central cough mechanism differs between disease states, creating differential drug responses 4
• Opioids demonstrate strong efficacy in chronic bronchitis/COPD but inconsistent results in upper respiratory infections 4
• This neural remodeling (plasticity) alters sensitivity of the central cough mechanism to pharmacologic agents 4