Antihistamines: models to assess sedative properties, assessment of sedation, safety and other side‐effects

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Abstract
Behavioural changes are produced by any drug that enters the central nervous system. These psychoactive effects include changes in alertness, concentration, attention, memory, cognition, psychomotor accuracy, skilled performance and affect. Changes in psychological performance may affect the safety of both the individuals taking the drug and of those people coming into contact with them. The aims of psychopharmacological performance tests are to describe the nature, extent and severity of these changes and identify drugs without deleterious effects upon performance. Use of traditional antihistamines 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. Firstly, an objectively determined one based on the results of psychometric tests from controlled trials and secondly, the subjects response to the administration of a drug. Although the second generation of antihistamines have a much more favourable therapeutic index, use of these agents has also been reported to cause varying degrees of sedation. As antihistamines are largely used by ambulant patients, a complete evaluation of sedation should be performed through standardized objective tests, shown to be sensitive to the central effects of antihistamines as well as reliable ratings of subjective experiences. An extensive review of the literature has identified a number of tests which appear to be sensitive to the central effects of antihistamines. These include tests of psychomotor performance, sensori‐motor co‐ordination speed, information processing, sensory skills as well as physiological measures and subjective rating scales. Using this battery of cognitive and psychomotor tests, it is evident that only a very limited number of antihistamines can claim to be virtually free of both objective and subjective sedative effects, although the second generation of antihistamines are generally less impairing than the original ones; when prescribed at their recommended doses.

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