Night-time sedating H1 -antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial

Abstract

Background: Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1 -antihistamine in the morning and a sedating first-generation H1 -antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded?

Objectives: To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria (CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy).

Methods: In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2 oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence.

Results: Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2 oL scores (P < 0·001) without significant differences between the two. Compared with baseline, daytime somnolence was significantly reduced by levocetirizine monotherapy (P = 0·006) but not by levocetirizine plus hydroxyzine (P = 0·218). Direct comparison of the two treatment modalities in terms of daytime somnolence favoured levocetirizine monotherapy (P = 0·026).

Conclusions: The widespread belief that sleep is aided by the addition of a sedating first-generation H1 -antihistamine, usually hydroxyzine, at night is not supported. These results are in line with the urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1 -antihistamines only.

Figure 1

Study design. The study consisted of two separate double-blind phases. Phase one was an in-hospital assessment of the effectiveness and tolerability of levocetirizine and hydroxyzine at two doses. Phase two was a comparison of levocetirizine monotherapy vs. levocetirizine plus hydroxyzine at night. Complete data were collected at baseline and at the end of each study period. Broken lines indicate collection of urticaria activity scores during the assessment period.

Figure 2

Chronic Urticaria Quality of Life Questionnaire (CU-Q₂oL) scores at the start of the study (baseline) and after 5 days of treatment with levocetirizine 15 mg daily + hydroxyzine 50 mg at night (Levo + Hydroxy) or levocetirizine 20 mg daily alone (Levo Monotherapy). The maximum possible score for CU-Q₂o Lis 92. Horizontal bars indicate median values. Significance of differences between treatments was calculated by Wilcoxon’s nonparametric test for paired data. NS, not significant.

Figure 3

Urticaria Activity Scores at the start of the study (baseline) and after 5 days of treatment with levocetirizine 15 mg daily + hydroxyzine 50 mg at night (Levo + Hydroxy) or levocetirizine 20 mg daily alone (Levo Monotherapy). Horizontal bars indicate median values. Significant differences between treatments were calculated by Wilcoxon’s nonparametric test for paired data. NS, not significant.

Figure 4

Visual analogue scale (VAS) scores for (a) night-time sleep disturbance and (b) daytime sedation at the start of the study (baseline) and after 5 days of treatment with levocetirizine 15 mg daily + hydroxyzine 50 mg at night (Levo + Hydroxy) or levocetirizine daily 20 mg alone (Levo Monotherapy). Horizontal bars indicate median values. Significant differences between treatments were calculated by Wilcoxon’s nonparametric test for paired data. NS, not significant.