title: Individual differences in central nervous system response to antihistamines (H1-receptor antagonists).
abstract: OBJECTIVE
  We hypothesized that the objectively documented central nervous system response to antihistamines (H1-receptor antagonists) could not be predicted reliably by an individual's subjective perception of somnolence after ingestion of these medications.
  
  
  METHODS
  In a double-blind, placebo-controlled, single-dose, four-way crossover study, cetirizine 10 mg, hydroxyzine 50 mg, diphenhydramine 50 mg, or placebo were administered to 20 healthy subjects. Before and two to two and one-half hours after dosing, the latency of the P300 event-related potential (P300) at the central (Cz) and parietal (Pz) scalp electrodes, and the visual analogue scale for somnolence were recorded. Epicutaneous tests with histamine were performed, and serum H1-receptor antagonist concentrations were also measured.
  
  
  RESULTS
  Neither cetirizine nor placebo significantly increased the mean P300 latency or somnolence as recorded on the visual analogue scale compared with predose baseline (P > .05), although increases were seen in some subjects after each of these treatments. Hydroxyzine and diphenhydramine increased the mean P300 latency and somnolence significantly (P < .05) compared with baseline; increases were observed in most, but not all subjects. Hydroxyzine increased P300 latency and somnolence significantly compared with placebo and with cetirizine. Diphenhydramine increased somnolence significantly compared with placebo. Overall, correlation between the objective test, P300 latency, and the subjective assessment, somnolence as recorded on the visual analogue scale, was statistically significant but clinically unimportant. Identification of central nervous system adverse effects after one potentially sedating H1-receptor antagonist did not predict central nervous system adverse effects after the others.
  
  
  CONCLUSIONS
  Inter-individual objective and subjective central nervous system responses to H1-receptor antagonists are wide-ranging. The subjective responses can be misleading and do not necessarily predict the abnormalities that can be documented objectively after the same H1-receptor antagonist or a different H1-antagonist.
authors.affiliation: Health Sciences Clinical Research Centre, Faculty of Medicine, University of Manitoba, Canada.
authors.forename: F E
authors.initials: FE
authors.lastname: Simons
authors.forename: T G
authors.initials: TG
authors.lastname: Fraser
authors.forename: J D
authors.initials: JD
authors.lastname: Reggin
authors.forename: K J
authors.initials: KJ
authors.lastname: Simons
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005071:Evoked Potentials / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011930:Reaction Time / Q000187:drug effects
chemical_list: D006634:Histamine H1 Antagonists