Codeine and cough: an ineffective gold standard

PURPOSE OF REVIEW: Cough is one of the most common reasons why patients visit physicians. The opioid codeine has been a mainstay in the treatment of cough for decades and this drug is widely regarded as the 'gold standard' cough suppressant. RECENT FINDINGS: Recent placebo-controlled studies have shown that codeine is no more effective than placebo in suppressing cough caused by either upper respiratory disorders or chronic obstructive pulmonary disease. These recent reports are not consistent with several older placebo-controlled studies that demonstrated the efficacy of codeine. The reasons for this difference are not fully understood. SUMMARY: We propose that these differences, as well as results from animal models, can be explained by the existence of a complex hierarchical control system that regulates the expression of coughing. This system, known as a holarchy, is composed of regulatory elements known as 'holons' that interact with one another to regulate cough. Based on work in animal models, codeine is proposed to act on an intermediate order holon that may not be critical for coughing under some situations in humans. Testing of this hypothesis and further elucidation of the control system for cough will represent an important direction for future research in this area.