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Use of Nonsedating Antihistamines in the Common Cold

Three Part Question

In patients [with a common cold] is [treatment with non-sedating antihistamines better than placebo] at [reducing of symptoms severity or duration]?

Clinical Scenario

An otherwise healthy 25 year old woman presents to the ER with 3 days of runny nose, sneezing, and nonproductive cough. She reports it feels like a common cold and usually she recovers without intervention. She has never received relief from over the counter cold medications. She is seeking care because she has a job interview in two days and wants to know if there is anything she can take to recover faster. You have heard that some providers use second generation antihistamines for upper respiratory infections, and wonder if there is any evidence behind the practice.

Search Strategy

Ovid MEDLINE(R) 1948 to March Week 4 2011. Embase via the NHS Evidence ‘Health Information Resources’ date of searching 04/04/11. The Cochrane Library April 2011.
[exp common-cold or exp respiratory-tract-infections/ or exp cough or exp nasal-obstruction or exp sneezing or exp rhinovirus] AND [exp cetirizine or exp loratadine or exp terfenadine or].

Cochrane:MeSH descriptor Common Cold explode all trees AND MeSH descriptor Histamine H1 Antagonists explode all trees 34 records 0 relevant. MeSH descriptor Common Cold explode all trees AND MeSH descriptor cetirizine explode all trees or MeSH descriptor Loratadine explode all trees or MeSH descriptor Terfenadine explode all trees or fexofenadine.ti.,ab. = 4 records 3 duplicates

Search Outcome

144 papers were identified on Medline and 12 on Embase, 4 were relevant to the clinical question. A Cochrane review was withdrawn in 2009 due to lack of update – but is still visible in archive online (1)

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Dicpinigaitis PV, Gayle YE.,
12 subjects with URTI and 12 healthy controls underwent capsaicin cough induction test before and after fexofenadine.Randomized controlled trial, although not for a clinical outcome.Amount of capsiacin to induce 5 coughsFexofenadine demonstrated no antitussive activityNot truly a clinical test, DOE instead of POE
Henauer and Glück,
91 adults with common cold symptoms randomized to terfenadine or placebo. Randomized, double blind, placebo control. Subjective rating of severity of nasal symptoms, mean nasal airflow, and rating on rhinoscopy. Terfenadine demonstrated a small improvement in symptoms and airflow.Original number of patients not enrolled, protocol broken during study, then re-designed around data.
Berkowitz and Tinkelman,
97 healthy adults with common cold symptoms randomized to terfenadine or placebo. Randomized, double blind, placebo controlled trial Subjective severity of symptoms and examination by physician.No significant difference between terfenadine and placebo; drug side effects were low in both groups Small sample size
Gaffey, Kaiser, Hayden,
250 healthy adults with common cold symptoms randomized to terfenadine or placebo.Randomized, double blind, placebo controlled trialSubjective report of severity of symptoms; adverse effectsNo significant differences between terfenadine and placebo. 16 subjects did not comply with study protocol


Given the prevalence of the common cold and the large number of patient encounters seeking relief, there is a relative scarcity of research. Histamine has been proposed in the pathogenesis of viral cold symptoms. Newer, non-sedating antihistamines have few adverse effects. No trials with loratadine or cetirizine were identified, although fexofenadine is thought to have an identical mechanism of action and terfenadine is a prodrug of fexofenadine. No studies confirmed the diagnosis virologically, but this is consistent with the clinical scenario where the ‘gold standard’ diagnosis in not indicated.

Clinical Bottom Line

There was no significant evidence found to support the practice of using second generation antihistamines for the common cold, but there were few negative studies either. Further patient oriented clinical research is required.


  1. De Sutter AIM, Lemiengre M, Campbell H. Antihistamines for the common cold (archive) accessed 18/04/11
  2. Dicpinigaitis PV, Gayle YE. Effect of the second-generation antihistamine, fexofenadine, on cough reflex sensitivity and pulmonary function. Br J Clin Pharmacol 2003;56:501-4.
  3. Henauer SA and Glück U. Efficacy of terfenadine in the treatment of common cold. A double-blind comparison with placebo. Eur J Clin Pharmacol 1988;34:35-40.
  4. Berkowitz RB and Tinkelman DG. Evaluation of oral terfenadine for treatment of the common cold. Ann Allergy 1991;67:593-7.
  5. Gaffey MJ, Kaiser DL, Hayden FG. Ineffectiveness of oral terfenadine in natural colds: evidence against histamine as a mediator or common cold symptoms. Pediatr Infect Dis J 1988;7:223-228