BACKGROUND: There is concern about the effect of antihistamines in children on alertness and school performance. This study assessed the impact of first- and second-generation antihistamines on school performance.
POPULATION STUDIED: The investigators enrolled 63 children aged 8 to 10 years with antihistamine-treated allergic rhinitis but no current symptoms. Subjects underwent skin testing to prove they were allergic to allergens not currently in season. They had no known learning disabilities or illnesses that might have an impact on the study. In general, the subjects seem similar to patients family physicians see, although no information about the study group composition by weight, sex, ethnicity, specific allergy history, or other medical history was given.
STUDY DESIGN AND VALIDITY: This was a double-blind placebo-controlled study. Participants were randomized to 1 of 3 treatment groups: diphenhdramine (Benadryl, dye-free) 25 mg twice daily, loratadine (Claritin) 10 mg in the morning with placebo in the evening, or placebo twice daily. To simulate an everyday classroom experience, an existing laboratory school was used on 3 consecutive weekends. The medications were administered on study days 1, 2, and 8 at 7:45 AM and 1:45 PM. The subjects were given 1-hour lectures and 1-hour reading assignments on plant biology. After 90 to 120 minutes, they completed computerized testing to assess retention and reaction times. Covariate analysis was performed, with adjustments for sex, age, baseline reading ability, and weight, along with correction for multiple comparisons. The methodology of this study was strong. The major strengths were the randomized design, the use of patients with known allergies, and the realistic laboratory school setting with appropriate and innovative “blinded” testing. The major weaknesses of the study were the relatively small sample size, and—despite the commendable efforts of the investigators—the inherent artificiality of a weekend school that takes place only over a few weekends. Other minor limitations include the short duration of the study and the lack of assessment of baseline medical history. Interpretation was hampered by the lack of information regarding the results of randomization.
OUTCOME MEASURED: Outcomes measured by computer assessment were: (1) retention of material presented orally (average number of errors in 25 questions about teacher presentations); (2) retention of materials presented in a written format (average number of errors in 25 questions from the readings); (3) reaction time for answers (average for all correct computer test questions); and (4) child self report of somnolence.
RESULTS: At the end of the trial, there were no significant differences noted in the verbal instruction score, reading test score, reaction time, or somnolence scale among students in the 3 treatment groups. Female subjects tended to rate somnolence slightly higher than male subjects did; heavier subjects rated somnolence lower.
This well-designed study provides good evidence that antihistamines, at least over the short term, do not impair retention of oral and written information, reaction time, or level of wakefulness in a school setting in asymptomatic children aged 8 to 10 years. There is no significant clinical difference between response to diphenhydramine and loratadine. Clinicians can use this evidence in discussing the risks and benefits of antihistamines with parents and to support their use in the treatment of allergic rhinitis in children. Further research is needed to address the impact of antihistamines in symptomatic children, in patients who need medications for longer periods of time, and on other kinds of learning.