Central nervous system effects of H-1-receptor antagonists in the elderly

Background: The potential adverse central nervous system effects of H-1-rec eptor antagonists have not been optimally studied in the elderly. Objective: We hypothesized that newer H-1-receptor antagonists such as ceti rizine and loratadine would cause less central nervous System dysfunction t han the older H-1-receptor antagonists diphenhydramine and chlorpheniramine in this population, as they do in younger subjects. Methods: We performed a randomized, double-blind, single-dose, placebo-cont rolled, 5-way crossover study in 15 healthy elderly subjects (mean age 71 /- SD 5 years). On study days at least 1 week apart, they received cetirizi ne 10 mg, loratadine 10 mg, diphenhydramine 50 mg, chlorpheniramine 8 mg, o r placebo. Outcome measures, recorded before and 2 to 2.5 hours after dosin g were latency of the P300 event-related potential in which increased laten cy reflects a decreased rate of cognitive processing, visual analogue scale for subjective somnolence, and histamine skin tests for measurement of per ipheral H-1-blockade. Results: The changes in P300 following each treatment yielded variances tha t were not equal (P > .05), precluding usual statistical analysis of the me ans. These variances were ranked: chlorpheniramine > diphenhydramine > lora tadine > placebo > cetirizine, The rank of mean differences in the visual a nalogue scale increase from pre-dose baseline was: diphenhydramine > chlorp heniramine > cetirizine > loratadine > placebo. All H-1-receptor antagonist s suppressed the histamine-induced wheal and flare significantly compared t o baseline. Conclusion: In the elderly, the new H-1-receptor antagonists cetirizine and loratadine are less likely to cause adverse central nervous system effects than the old H-1-antagonists chlorpheniramine or diphenhydramine, but this requires confirmation using additional objective tests of central nervous system function.