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Adverse central nervous system effects of older antihistamines in children
F E Simons1, T G Fraser, J D Reggin
1Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Insights
First-generation antihistamines like diphenhydramine and hydroxyzine effectively block histamine receptors but impair cognitive function and cause somnolence in children. These central nervous system (CNS) effects are significant, impacting children
Area of Science:
- Pediatric Pharmacology
- Neuroscience
- Allergy and Immunology
Background:
- First-generation antihistamines are widely used in children.
- Potential central nervous system (CNS) effects of these medications in young subjects are not well-documented.
- Hypothesis: Diphenhydramine and hydroxyzine adversely affect CNS function in children.
Purpose of the Study:
- To evaluate the effects of diphenhydramine and hydroxyzine on central and peripheral histamine H1-receptors in children.
- To objectively assess cognitive processing impairment.
- To subjectively assess somnolence.
Main Methods:
- Double-blind, single-dose, three-way crossover study with 15 allergic rhinitis subjects.
- Assessment of cognitive processing via P300 event-related potential latency.
- Assessment of somnolence using a visual analog scale.
- Evaluation of peripheral H1-blockade by histamine-induced wheal and flare suppression.
Main Results:
- Diphenhydramine and hydroxyzine significantly increased P300 latency at central (Cz) and frontal (Fz) electrodes.
- Hydroxyzine significantly increased somnolence; diphenhydramine showed a similar trend.
- Both antihistamines significantly reduced histamine-induced wheals and flares compared to baseline and placebo.
Conclusions:
- Diphenhydramine and hydroxyzine are effective H1-receptor antagonists in children.
- These antihistamines cause CNS dysfunction in children, indicated by increased P300 latency (cognitive function) and somnolence.
- Clinical use of these medications in children warrants consideration of their CNS side effects.
Abstract:
Although older, potentially sedating, "first-generation" antihistamines (H1-receptor antagonists) are commonly used in childhood, their central nervous system (CNS) effects have not been well-documented in young subjects. We hypothesized that diphenhydramine and hydroxyzine would affect CNS function adversely in this population. Our objective was to evaluate the effects of these medications on central and peripheral histamine H1-receptors in children. Fifteen subjects with allergic rhinitis were tested before and 2-2.5 h after administration of diphenhydramine, hydroxyzine, or placebo in a double-blind, single-dose, three-way crossover study. Impairment of cognitive processing was assessed objectively by the latency of the P300 event-related potential (P300). Somnolence was assessed subjectively by a visual analog scale. Peripheral H1-blockade was assessed by suppression of the histamine-induced wheals and flares. At the central (Cz) and frontal (Fz) electrodes, diphenhydramine and hydroxyzine increased the P300 latency significantly (P < 0.05) compared to baseline. Hydroxyzine increased somnolence, as recorded on the visual analog scale, significantly compared to baseline (P < 0.05), with a similar trend for diphenhydramine (P = 0.07). Both antihistamines reduced histamine-induced wheals and flares significantly compared to baseline and compared to placebo. In children, diphenhydramine and hydroxyzine are effective H1-receptor antagonists, but both these medications cause CNS dysfunction, as evidenced by increased P300 latency, a measure of cognitive function, and by increased subjective somnolence.