Antihistamines and Sedation: Methods and Measures.

A critical review of the clinical literature surveying subjective reports of sedation following administration of antihistamines (AH's) showed that some substances were perceived as more sedative than others. When a review was undertaken of standardised, objective and subjective, psychometric assessments of sedation used in experimental studies the results were broadly equivocal but no particular psychometric appeared to encapsulate the sedative activity of certain AH's. A series of controlled experiments, primarily in non-atopic volunteers, investigated various aspects of the methods and measures used to assess sedation following AH administration. These included studies investigating the impact of dose response relationship, time course of drug activity, route of administration, single versus repeated administration, sleep induction, possible interaction with other substances, and allergen induced histamine release. It was hoped that it would be possible to identify a particular protocol which would prove to be the most efficacious and valid way of evaluating sedation following AH's. However, there were three factors which mitigated against such parsimony, namely: the lack of sensitivity and reliability of the psychometrics, the inter-drug/dose regimen differences in the magnitude of the sedation produced, and, perhaps most importantly, the interindividual variation in sensitivity to the sedative effects of HI receptor antagonists