Long-Term Evaluation of the Impact of the H1-Receptor Antagonist Cetirizine on the Behavioral, Cognitive, and Psychomotor Development of Very Young Children with Atopic Dermatitis

Abstract

The impact of the prolonged use of cetirizine at high dose (0.25 mg/kg twice a day over 18 mo) on behavior and cognitive ability was examined in a double-blind, randomized, placebocontrolled trial (ETAC-Early Treatment of the Atopic Child) designed to establish whether it was possible to prevent young children (1-2 y old at study entry) with atopic dermatitis from developing asthma. Well-validated and standardized measures of behavior (Behavior Screening Questionnaire) and cognition (McCarthy Scales of Children's Abilities) were used. In addition, the ages of attainment of psychomotor milestones were established. These measures were taken between an average of 32 and 53 mo of age, both during the study treatment with cetirizine or placebo and after the study treatment had been discontinued. The Behavior Screening Questionnaire was completed at least once on approximately 300 children in each group and on approximately 200 children on five occasions. The McCarthy Scales of Children's Abilities were administered to approximately 100 in each group at three different times. There were no significant differences between the cetirizine and placebo groups on either of the behavior and cognition measures or in psychomotor milestones during or after the study treatment. These findings suggest that there are no adverse effects on behavior or learning processes associated with the prolonged use of cetirizine in young children with atopic dermatitis. There is evidence that the use of some antihistamines has an effect on behavior and that this is shown most markedly as sedation (1-3). These side effects may have implications for the long-term development of the child. Little is known about the development of histamine receptors with age, and, given that all antihistamines can gain access to the brain (4), it is important to establish whether antihistamines have a deleterious effect on histamine receptor sites and on the cognitive and behavioral systems regulated by histamine (5). There has been no study on the impact of the long-term administration of antihistamines on children's behavioral development. The present study aimed to fill this gap.A number of findings that have suggested that firstgeneration antihistamines can interfere with learning. Sedating (diphenhydramine) and nonsedating (loratadine) antihistamines and a placebo have been used with children suffering from seasonal allergic rhinitis (6). It was found that those on placebo and diphenhydramine learned significantly less well than healthy controls. The nonsedating antihistamine only partially counteracted this effect. A subsequent study of young adults with seasonal allergic rhinitis showed that this learning deficit could be avoided by the use of a combination compound of acrivastine and pseudoephedrine (7). The indications from these previous studies made it essential to determine whether

Central Nervous System Side Effects of First- and Second-Generation Antihistamines in School Children With Perennial Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Comparative Study

“…In the Early Treatment of the Atopic Child study, subjects were given either cetirizine 0.25 mg/kg twice daily or placebo over 18 months. 33 No significant differences were noted between the treatment and placebo groups in behavioral measures, cognitive measures (McCarthy Scales of Children's Abilities), or age of attainment of psychomotor milestones during or after the study treatment. However, these are gross measures of CNS function and may not detect subtle effects of sedation.…”

Effects of sedative and nonsedative antihistamines on prefrontal activity during verbal fluency task in young children: a near-infrared spectroscopy (NIRS) study

“…For example, it has been reported that sedative effects were not observed in school-aged children after administration of terfenadine (Simons et al 1996), fexofenadine (Simons et al 2003), and levocetirizine (Simons and Simons 2005). Moreover, Stevenson et al (2002) found that there were no adverse effects on behavioral or learning processes associated with prolonged use of cetirizine in young children even though this drug causes mild sedative effects in that population (Ng et al 2004). These observations are consistent with our findings that epinastine did not diminish behavioral performance and prefrontal NIRS response in the verbal fluency task.…”

Clinical and Pharmacological Peculiarities of Cetirizine Use for the Therapy of Allergic Diseases in Children

“…Out of the 2 nd generation antihistamines, drowsiness was most frequently reported in the cetirizine group [16]. A randomized double-blind placebo-controlled study of 600 children with atopic dermatitis at the age of 12-24 months demonstrated that the intake of 0.25 mg/kg of cetirizine BID over a period of 18 months did not affect behavior and cognitive function both during the study and in the follow-up period [17]. A large multicenter study conducted by the Early Treatment of the Atopic Child (ETAC) estimated the safety of long-term intake of cetirizine drops (10 mg/ml) by children aged 12-24 months over an 18-month long treatment and 18-month-long follow-up period.…”