BACKGROUND: Currently available over-the-counter cough remedies historically have been criticized for lack of scientific evidence supporting their efficacy. Although the first-generation antihistamine diphenhydramine is classified as an antitussive by the United States Food and Drug Administration, to the authors' knowledge it has never been shown to inhibit cough reflex sensitivity in subjects with pathological cough.
OBJECTIVE: To evaluate the effect of diphenhydramine on cough reflex sensitivity.
SETTING: Montefiore Medical Center, an academic medical center in New York City.
METHODS: Twenty two subjects with acute viral upper respiratory tract infection (common cold) underwent cough reflex sensitivity measurement employing capsaicin challenge on 3 separate days, 2 h after ingesting single doses of 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 standard endpoint of cough challenge was used: concentration of capsaicin inducing ≥5 coughs (C5).
MAIN OUTCOME MEASURE: Effect on cough reflex sensitivity (C5).
RESULTS: A significant difference (p = 0.0024) was established among groups, with pairwise analysis revealing a significant increase in mean log C5 (0.4 ± 0.55 (SD); p < 0.01) for the diphenhydramine-containing medication versus placebo, but not for dextromethorphan versus placebo.
CONCLUSIONS: Our results provide the initial evidence of the ability of diphenhydramine to inhibit cough reflex sensitivity in subjects with acute pathological cough. Timing of cough reflex sensitivity measurement may not have allowed demonstration of maximal antitussive effect of dextromethorphan.
IMPORTANCE: Cough is one of the most common reasons why children visit a health care professional. OBJECTIVES: To compare the effect of a novel formulation of pasteurized agave nectar vs placebo and no treatment on nocturnal cough and the sleep difficulty associated with nonspecific acute cough in infants and toddlers. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial performed in 2 university-affiliated outpatient, general pediatric practices from January 28, 2013, through February 28, 2014, children 2 to 47 months old with nonspecific acute cough duration of 7 days or less were studied. Surveys were administered to parents on 2 consecutive days, the day of presentation (when no medication had been given the prior evening) and the next day (when agave nectar, placebo, or no treatment had been administered to their child before bedtime) according to a partially double-blind randomization scheme. INTERVENTIONS: A single dose of agave nectar, placebo, or no treatment administered 30 minutes before bedtime. MAIN OUTCOMES AND MEASURES: Cough frequency, cough severity, cough bothersomeness, congestion severity, rhinorrhea severity, and cough effect on child and parent sleep. RESULTS Significant differences in symptom improvement were detected between the study groups (P < .05 for all, except P = .06 for cough bothersomeness), with agave nectar and placebo proving to be superior to no treatment, but no significant differences for any outcome were found when comparing agave nectar against placebo. CONCLUSIONS AND RELEVANCE: In a comparison of agave nectar, placebo, and no treatment, a placebo effect was demonstrated, with no additional benefit offered by agave nectar. Health care professionals should consider the potential benefits and costs when recommending a treatment with only a placebo effect for infants and toddlers with nonspecific acute cough. Copyright 2014 American Medical Association. All rights reserved.
Currently available over-the-counter cough remedies historically have been criticized for lack of scientific evidence supporting their efficacy. Although the first-generation antihistamine diphenhydramine is classified as an antitussive by the United States Food and Drug Administration, to the authors' knowledge it has never been shown to inhibit cough reflex sensitivity in subjects with pathological cough.
OBJECTIVE:
To evaluate the effect of diphenhydramine on cough reflex sensitivity.
SETTING:
Montefiore Medical Center, an academic medical center in New York City.
METHODS:
Twenty two subjects with acute viral upper respiratory tract infection (common cold) underwent cough reflex sensitivity measurement employing capsaicin challenge on 3 separate days, 2 h after ingesting single doses of 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 standard endpoint of cough challenge was used: concentration of capsaicin inducing ≥5 coughs (C5).
MAIN OUTCOME MEASURE:
Effect on cough reflex sensitivity (C5).
RESULTS:
A significant difference (p = 0.0024) was established among groups, with pairwise analysis revealing a significant increase in mean log C5 (0.4 ± 0.55 (SD); p < 0.01) for the diphenhydramine-containing medication versus placebo, but not for dextromethorphan versus placebo.
CONCLUSIONS:
Our results provide the initial evidence of the ability of diphenhydramine to inhibit cough reflex sensitivity in subjects with acute pathological cough. Timing of cough reflex sensitivity measurement may not have allowed demonstration of maximal antitussive effect of dextromethorphan.
