INDIVIDUAL-DIFFERENCES IN CENTRAL-NERVOUS-SYSTEM RESPONSE TO ANTIHISTAMINES (H-1-RECEPTOR ANTAGONISTS)

Hypothesis: We hypothesized that the objectively documented central ne rvous system response to antihistamines (H-1-receptor antagonists) cou ld not be predicted reliably by an individual's subjective perception of somnolence after ingestion of these medications. Methods: In a doub le-blind, placebo-controlled, single-dose, four-way crossover study, c etirizine 10 mg, hydroxyzine 50 mg, diphenhydramine 50 mg, or placebo were administered to 20 healthy subjects, Before and two to two and on e-half hours after dosing, the latency of the P300 event-related poten tial (P300) at the central (Ct) and parietal (Pt) scalp electrodes, an d the visual analogue scale for somnolence were recorded. Epicutaneous tests with histamine were performed, and serum H-1-receptor antagonis t concentrations were also measured. Results: Neither cetirizine nor p lacebo 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 th ese treatments. Hydroxyzine and diphenhydramine increased the mean P30 0 latency and somnolence significantly (P<.05) compared with baseline; increases were observed in most, but not all subjects. Hydroxyzine in creased P300 latency and somnolence significantly compared with placeb o and with cetirizine. Diphenhydramine increased somnolence significan tly compared with placebo. Overall, correlation between the objective test, P300 latency, and the subjective assessment, somnolence as recor ded on the visual analogue scale, was statistically significant but cl inically unimportant. Identification of central nervous system adverse effects after one potentially sedating H-1-receptor antagonist did no t predict central nervous system adverse effects after the others, Con clusions: Inter-individual objective and subjective central nervous sy stem responses to H-1-receptor antagonists are wide-ranging. The subje ctive responses can be misleading and do not necessarily predict the a bnormalities that can be documented objectively after the same H-1-rec eptor antagonist or a different H-1-antagonist.