What is the efficacy of dextrometorphan (cough suppressant) compared to placebo for cough relief in adults?

Efficacy of Dextromethorphan for Cough Relief in Adults

Dextromethorphan has modest efficacy as a cough suppressant in adults with acute cough, with maximum cough reflex suppression occurring at 60 mg doses, though commonly available over-the-counter preparations typically contain subtherapeutic doses. 1, 2

Mechanism and Evidence of Efficacy

• Dextromethorphan is a non-sedating opiate that acts centrally to suppress the cough reflex 1, 2
• A dose-response relationship exists, with maximum cough reflex suppression occurring at 60 mg, which can provide prolonged relief 1, 2
• Dextromethorphan has been shown to suppress acute cough in a meta-analysis, though evidence from clinical studies is limited due to the variable and episodic nature of acute cough 1
• In objective laboratory studies using cough challenge methodologies, dextromethorphan demonstrates significant suppression of the cough reflex 3

Comparative Efficacy vs. Placebo

• When comparing objective measures like cough reflex sensitivity to citric acid, dextromethorphan (30 mg) significantly increases the threshold for cough compared to placebo 3
• However, in real-world clinical settings, subjective improvements in cough symptoms often show minimal differences between dextromethorphan and placebo, suggesting a strong placebo effect in cough treatment 3, 4
• A study of patients with acute upper respiratory tract infection found that a single 30 mg dose of dextromethorphan showed little difference from placebo in reducing cough frequency or subjective cough severity scores 4

Dosing Considerations

• Standard over-the-counter preparations typically contain subtherapeutic doses of dextromethorphan 1, 2
• Caution must be exercised when recommending higher doses (e.g., 60 mg) as many preparations combine dextromethorphan with other ingredients like paracetamol 1, 2
• Oral administration appears more effective than inhaled administration for cough suppression 5

Safety Profile

• Dextromethorphan has a favorable safety profile compared to other antitussives like codeine 6, 7
• Adverse reactions are infrequent and usually not severe, primarily consisting of neurological, cardiovascular, and gastrointestinal disturbances that are typically dose-related 6
• In a direct comparison with codeine (20 mg), dextromethorphan (20 mg) was similarly effective in reducing cough frequency but superior in reducing cough intensity 7
• Dextromethorphan lacks the significant adverse side effect profile of opiate antitussives like codeine or pholcodine 1, 7

Clinical Application and Alternatives

• For acute viral cough, which is usually self-limiting, simple remedies like honey and lemon may be as effective as pharmacological treatments 1, 2
• Other effective cough suppressants include:
  • Menthol by inhalation (provides acute but short-lived cough suppression) 1
  • Sedative antihistamines (particularly useful for nocturnal cough but cause drowsiness) 1
• Codeine or pholcodine are not recommended due to their adverse side effect profiles despite similar efficacy to dextromethorphan 1, 2

Common Pitfalls and Caveats

• The disconnect between objective laboratory measures of cough suppression and subjective patient-reported outcomes suggests limitations in how we evaluate antitussive efficacy 3, 4
• The strong placebo effect in cough treatment may account for much of the perceived benefit of over-the-counter cough medications 3
• Dextromethorphan should not be co-administered with monoamine oxidase inhibitors (MAOIs) due to safety concerns 6
• Women may experience different responses to cough medications due to increased sensitivity of the cough reflex compared to men 1