What is the evidence that codeine (opioid cough suppressant) is effective for treating chronic cough?

Codeine Has Limited Efficacy for Chronic Cough with Potential Risks

Codeine is not recommended for chronic cough due to limited evidence of efficacy and significant side effect concerns. 1

Evidence on Codeine for Chronic Cough

• Codeine and other central cough suppressants have only shown intermediate benefit for short-term symptomatic relief of coughing in chronic bronchitis, but not for general chronic cough (Grade of recommendation B) 1
• Opiate antitussives, including codeine, have a significant adverse side effect profile and are not recommended for general chronic cough management 1
• Recent research shows that while codeine may be more effective than levodropropizine in reducing cough severity (based on VAS, CSS, and LCQ scores), it comes with more frequent adverse events including drowsiness, constipation, and headaches 2

Efficacy Considerations

• A systematic review found that opioids (including codeine) demonstrated some efficacy for chronic cough in adults with effect sizes of 0.55 for cough severity and 0.57 for cough frequency compared to placebo, but the overall strength of evidence was limited by inconsistency and imprecision 3
• Despite being prescribed in real-world practice (sometimes for >8 weeks), there is limited robust clinical evidence on codeine's long-term efficacy for chronic cough 4
• In a real-world analysis, only 40.1% of patients prescribed codeine reported improvement in their chronic cough, while 21.2% reported no improvement, and side effects were noted in 7.8% of patients 4

Safety Concerns

• Codeine has known risks including respiratory drive suppression, potential for addiction, and variable metabolic responses that can lead to unpredictable effects 5
• Treatment-related adverse events are more frequent with codeine than with peripheral cough suppressants like levodropropizine 2
• For children, codeine is contraindicated for those under 12 years of age due to safety concerns, and there is no evidence to support its use for chronic cough in pediatric populations 5

Alternative Approaches

• Peripheral cough suppressants such as levodropropizine and moguisteine are recommended for short-term symptomatic relief of coughing in chronic bronchitis with substantial benefit (Grade of recommendation A) 1
• Ipratropium bromide is the only inhaled anticholinergic agent recommended for cough suppression in patients with cough due to chronic bronchitis (Grade of recommendation A) 1
• For patients with severe airflow obstruction or frequent exacerbations of chronic bronchitis, inhaled corticosteroid therapy should be considered as it has been shown to reduce exacerbation rates and cough 6

Clinical Algorithm for Chronic Cough Management

1. First, address underlying causes of chronic cough (when identifiable) 7
2. For symptomatic relief in chronic bronchitis:
   • Start with ipratropium bromide as first-line therapy 1
   • Consider peripheral cough suppressants (levodropropizine, moguisteine) for short-term relief 1
   • Use codeine only as a short-term option when other treatments fail, with careful monitoring for side effects 2, 4
3. For patients with severe airflow limitation or frequent exacerbations:
   • Consider inhaled corticosteroids or combination therapy with long-acting β-agonist plus inhaled corticosteroid 6

Common Pitfalls

• Prescribing codeine for extended periods without reassessing the underlying cause of persistent cough 4
• Failure to monitor for side effects when using codeine, which can include drowsiness, constipation, and respiratory depression 2
• Overlooking more effective and safer alternatives for specific cough etiologies 1