Older-generation antihistamines and cough due to upper airway cough syndrome (UACS): efficacy and mechanism.

Older-generation H1 antihistamines are recommended in empiric protocols for the treatment of cough due to upper airway cough syndrome (UACS). Data from double-blind placebo-controlled trials that support the use of older-generation antihistamines in UACS are limited to a single study of cough due to the common cold. However, several empiric trials strongly support efficacy of older-generation antihistamines in patients with chronic cough. Data from a variety of studies support the concept that newer-generation H1 antihistamines are not useful in the treatment of cough due to UACS. The mechanism of action of older-generation H1 antihistamines has been proposed to be anticholinergic activity, but the rank order potency of these drugs as muscarinic receptor antagonists is not consistent with this hypothesis. Actions of these drugs on histamine H1 and/or nonhistaminergic receptors in the central nervous system remain a possible explanation for their effects on cough due to UACS. The effects of older H1 antihistamines may also be molecule specific, rather than attributable to the entire class of compounds. Additional studies should be performed to document the activity of these drugs in double-blind placebo-controlled trials.