The Psychopharmacology of Antihistamines: Indices of Behavioral Toxicity*

Although second-generation antihistamines generally penetrate the blood-brain barrier to a lesser degree than the powerfully impairing firstgeneration antihistamines, many have been found to produce dose-related impairment of central nervous system (CNS) function. In contrast, fexofenadine has been determined to be truly nonimpairing, even at supraclinical doses. Crossover studies using placeboand positivecontrolled objective tests of impairment showed that choice reaction time, sensorimotor coordination, information processing, car driving skills, and electrophysiologic measures were unaffected in patients taking fexofenadine. In addition, recent positron-emission tomography studies have provided further evidence that fexofenadine does not penetrate the blood-brain barrier. Therefore, in terms of CNS function, fexofenadine can be differentiated from the other currently available antihistamines. (Advanced Studies in Medicine. 2002;2(24):867-871) A ny central nervous system (CNS) side effects caused by pharmacologic therapy can have important safety and quality-of-life implications. Histamine has been widely reported to play an important role in maintaining CNS arousal and alertness. Therefore, antihistamines that cross the blood-brain barrier and antagonize histamine-1 (H1)-receptors in the brain can produce impairment of cognitive functions, including attention, memory, sensorimotor coordination, information processing, and psychomotor performance. These are related to the informationprocessing demands of all human day-to-day activities and functions, and therefore, administration of agents that cross the blood-brain barrier and impair CNS functions may lead to serious issues of patient safety as well as affect the quality of life of patients. For example, CNS impairment will not only impair the ability to drive and operate machinery, but will affect activities such as classroom learning, causing patients to feel tired, sleepy, and unable to concentrate. Evidence from epidemiologic studies has begun to determine a relationship between an increased incidence of automobile accidents and the administration of antihistaminergic agents; 3% of patients involved in fatal road traffic accidents (RTA) were found to have previously taken an antihistamine. Furthermore, 72% of patients who have used an antihistamine and subsequently been involved in a fatal RTA have been determined to be culpable, compared with 86% of those who had consumed alcohol. It has also been suggested that, cerebral H1blockade is associated with falls in the elderly.