Efficacy of diphenhydramine against cough in humans: a review

Pharm World Sci. 2007 Dec;29(6):577-83. doi: 10.1007/s11096-007-9122-2. Epub 2007 May 8.


Aim: To determine the efficacy of diphenhydramine against cough due to respiratory infection or irritation in patients/subjects without comorbidities.

Method: Two reviewers independently identified English language studies, searching on: clinical trials, randomized, diphenhydramine (OR dimenhydrinate), antitussive agents, cough (combine using AND). Sources were: Medline (1966-2005), Embase (1980-2005), Cochrane and references from retrieved articles. Two other reviewers, blinded to study origin selected studies, inclusion criteria being: diphenhydramine monotherapy against placebo, double-blinded, randomized, clinical trial, intention-to-treat, dropout information. The blinded reviewers evaluated the selected studies on a quality scale.

Results: Eleven articles were identified, 7 were rejected (4 not placebo controlled, 2 had no diphenhydramine, 1 not blinded), leaving 4 articles, that were included in the evaluation and scored 20, 21, 25 and 26 out of a maximum of 32. In these selected studies, a total of 162 people were examined, 65 on diphenhydramine, 63 on placebo and 34 in a crossover setting. There was a total of 13 dropouts. The crossover studies demonstrated significant effect; 27-56% reduction in 20 healthy volunteers and 21-26% reduction in 13 patients (originally 14, one outlier left out), whereas the active versus placebo studies did not.

Conclusion: In spite of the 60 years that the substance has been on the market, only few studies have properly evaluated the effect of diphenhydramine against cough. Presumptions about efficacy of diphenhydramine against cough in humans are not univocally substantiated in literature.

Publication types

  • Review

MeSH terms

  • Cough / drug therapy*
  • Diphenhydramine / therapeutic use*
  • Humans


  • Diphenhydramine