Sedation and antihistamines: a review of inter-drug differences using proportional impairment ratios.
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 and subjective tests, shown to be sensitive to the central effects of AHs.An extensive review of the literature identified 76 studies of H(1) receptor antagonists in healthy volunteers, in which assessment of sedation was the primary objective. Results from studies published in peer-reviewed journals which employed a placebo condition as well as a positive internal control using a crossover design were analysed to determine the extent to which a particular antihistamine produced impairments on a battery of psychometric tests. The impairment index for each antihistamine was calculated and subsequently compared with the impairment index obtained for all other AHs.The calculation of this proportional impairment ratio enabled the sedative potential of an individual antihistamine to be identified relative to all other AHs and thus allowed the ranking of AHs with respect to their ability to cause impairments of cognitive and psychomotor function.Findings from this review clearly demonstrate that there are distinct classes of AHs with respect to their ability to impair cognitive function and psychomotor performance. Copyright 2000 John Wiley & Sons, Ltd.
Shamsi
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HPRU Medical Research Centre, University of Surrey, Egerton Road, Guildford GU2 5XP, Surrey, UK.
Hindmarch
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