Abstract
The use of antihistamines (AHs) has until recently been associated with a number of undesirable side effects, the most troublesome of which is sedation. There are two aspects to sedation. The first, an objectively determined measure based on the results of psychometric tests from controlled trials, and the second, the subject's response to the administration of a drug. Since AHs are largely used in ambulant patients, a complete evaluation of sedation should be performed through standardised objective tests, shown to be sensitive to the central effects of AHs and reliable ratings of subjective experiences. A critical review of the literature on the experimental studies with AHs revealed that the traditional AHs had a greater propensity to produce adverse central nervous system (CNS) effects, whereas the so called second generation AHs were generally less impairing when administered within their recommended 'dose window'. A similar review of the clinical literature surveying subjective reports of sedation following the administration of AHs showed that the traditional AHs were perceived as more sedative than the second generation AHs. On the basis of these findings, a series of controlled experiments in non-atopic volunteers investigated the effects of a number of second generation AHs on various aspects of cognitive functioning and psychomotor performance. It is concluded that the second generation AHs have a lesser effect with respect to objective indices of sedation when compared to their predecessors, and that fexofenadine, has a claim to be the first truly non-sedating antihistamine as there is no objective evidence of CNS effects. The identification of an antihistamine, devoid of adverse CNS activity regardless of the administered dose, highlights the need for the introduction of a 'third generation' of AHs.