Clinical cough VI: the need for new therapies for cough: disease-specific and symptom-related antitussives.

Cough is a common symptom that can be self-limiting or persistent. Ideally, treatment of the underlying cause(s) of cough with specific treatments should eliminate cough. This approach may not be successful if no cause can be established or if the treatment of the cause fails. Suppression of cough may be disease-specific or symptom-related. There has been a long tradition in acute cough usually due to upper respiratory tract infections to use symptom-related antitussives. In chronic cough, suppression of cough may be achieved by disease-specific therapies, but in many patients it may be necessary to use symptomatic antitussives. The efficacy of some over-the-counter symptomatic antitussives is often no better than that of a placebo. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, pholcodeine, and dextromethorphan. Early studies reported success in reducing cough in patients with chronic bronchitis or chronic obstructive pulmonary disease (COPD); however, a carefully conducted blinded controlled study showed no effect of codeine on cough of COPD. Success with these cough suppressants may be achieved at high doses that are associated with side effects. A slow-release preparation of morphine has been shown to have some degree of efficacy, but this should be reserved for the most severe chronic cough patient, and for patients with terminal cancer who may also benefit from its analgesic effects. There are case reports of the success of centrally acting drugs such as amitriptyline, paroxetine, gabapentin, and carbamezepine in chronic cough. New agents derived from basic research such as new opioids such as nociceptin or antagonists of transient receptor potential vanniloid-1 may turn out to have antitussive effects. Efficacy of symptomatic cough suppressants must be tested in double-blind randomized trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough need effective antitussives that could be used either on demand or on a long-term basis.