title: Sedation and performance impairment of diphenhydramine and second-generation antihistamines: a meta-analysis.
abstract: BACKGROUND
  Antihistamines are among the most frequently used medications in the United States. Despite dramatically higher cost, second-generation antihistamines are replacing diphenhydramine because of the perception that they are not constrained by its sedating effects.
  
  
  OBJECTIVE
  We sought to examine, through meta-analytic procedures, the collective evidence regarding the sedating and performance-impairing effects of diphenhydramine relative to placebo and second-generation antihistamines.
  
  
  METHODS
  A search that began with the MEDLINE database was limited to those studies that included patients with atopic disease and control subjects, were blinded and randomized clinical trials, objectively examined alertness and psychomotor performance, reported means and variances, and were written in English. Information was systematically abstracted from the resulting 18 articles, and effect size was calculated.
  
  
  RESULTS
  Diphenhydramine impaired performance relative to placebo control and second-generation antihistamines, including acrivastine, astemizole, cetirizine, fexofenadine, loratadine, and terfenadine. However, results were quite varied, the average sedating effect of diphenhydramine was modest, and in some instances results of tests of performance in the diphenhydramine group showed less sedation than in the control or second-generation antihistamine groups. A significant (P <.05) average effect size indicated a mild sedating effect caused by second-generation antihistamines in comparison with placebo.
  
  
  CONCLUSIONS
  The absence of a consistent finding of diphenhydramine-induced sedation is surprising given that most studies have been designed to increase the probability of this outcome, including administering a 50-mg dose. On the basis of this meta-analysis of performance-impairment trials, a clear and consistent distinction between sedating and nonsedating antihistamines does not exist.
authors.affiliation: National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Bender
authors.forename: Shaun
authors.initials: S
authors.lastname: Berning
authors.forename: Rosalind
authors.initials: R
authors.lastname: Dudden
authors.forename: Henry
authors.initials: H
authors.lastname: Milgrom
authors.forename: Zung Vu
authors.initials: ZV
authors.lastname: Tran
mesh_terms: D004155:Diphenhydramine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic
chemical_list: D006634:Histamine H1 Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating; D006993:Hypnotics and Sedatives; D004155:Diphenhydramine