Although the first-generation antihistamine – diphenhydramine, is classified as an antitussive by the United States Food and Drug Administration, it has rarely been shown to inhibit cough reflex sensitivity in subjects with pathological cough.

A study published in the International Journal of Clinical Pharmacy evaluated the effect of diphenhydramine on cough reflex sensitivity.

Here, 22 subjects with acute viral upper respiratory tract infection (common cold) underwent cough reflex sensitivity measurement employing capsaicin challenge on three separate days, two hours after ingesting single doses of the study drug—to coincide with peak blood concentrations, administered in randomized, double-blind manner—a multicomponent syrup containing diphenhydramine (25 mg), phenylephrine (10 mg), in a natural cocoa formulation; dextromethorphan (30 mg) syrup; and, placebo syrup.

The results revealed a significant difference among groups, with pairwise analysis depicting marked increase in mean log concentration of capsaicin inducing ≥5 coughs, for the diphenhydramine-containing medication versus placebo, but not for dextromethorphan versus placebo.

Hence, the findings provided initial evidence of the ability of diphenhydramine to inhibit cough reflex sensitivity in subjects with acute pathological cough. However, timing of cough reflex sensitivity measurement may not have allowed demonstration of maximal antitussive effect of dextromethorphan.

Source: International Journal of Clinical Pharmacy. 2015 Jun;37(3):471-4. doi: 10.1007/s11096-015-0081-8.