OTC Diphenhydramine for Cough: The Evidence Is in

Regulators and stakeholders frequently debate the utility and effectiveness of OTC cough preparations. In light of some research findings, or lack thereof, the FDA has made some changes to its related recommendations over the last few years.

The FDA classifies the first-generation antihistamine diphenhydramine as an antitussive, and most OTC cough preparations contain either diphenhydramine or dextromethorphan. Citing a lack of evidence that diphenhydramine suppresses cough, researchers from the Albert Einstein College of Medicine and Montefiore Medical Center conducted a study to determine the drug’s effectiveness.

They evaluated diphenhydramine’s effect on cough reflex sensitivity in 22 subjects with acute viral upper respiratory tract infection. The study design was double-blind and participants were randomized to receive multi-component syrups containing:

· Diphenhydramine 25 mg and phenylephrine 10 mg, which has no antitussive action but is often paired with diphenhydramine in OTC preparations,

· Dextromethorphan 30 mg, or

· Placebo syrup

The researchers challenged the participants with capsaicin on 3 separate days, 2 hours after they took single doses of the study drugs or placebo. Scheduling the challenge at the 2-hour point ensured that patients had peak blood concentrations of diphenhydramine.

The results, which were published in the online version of the International Journal of Clinical Pharmacy, indicated that diphenhydramine works, as patients were less likely to cough when challenged with capsaicin if they had taken the diphenhydramine-containing formulation, compared with the dextromethorphan or placebo.

The researchers noted that they administered both active agents at standard doses and at 2 hours after dosing. Since maximal inhibition of capsaicin cough sensitivity by dextromethorphan may take 6 hours to develop, this finding has a limitation.

Another limitation was that the researchers were unable to blind the 3 formulations completely. Participants knew they would receive 2 active medications and a placebo over the study period, but did not know which flavors were associated with various interventions.

Overall, the study supported diphenhydramine’s use as an OTC antitussive.