Histamine H1 blocker hydroxyzine improves sleep in patients with cirrhosis and minimal hepatic encephalopathy: a randomized controlled pilot trial

Am J Gastroenterol. 2007 Apr;102(4):744-53. doi: 10.1111/j.1572-0241.2006.01028.x. Epub 2007 Jan 11.


Objectives: Sleep difficulty is common in minimal hepatic encephalopathy (HE) and the mechanisms are not fully elucidated. Dysregulated histamine neurotransmission is associated with an altered circadian rhythmicity that is partially restored following central histamine H1 receptor blockade in cirrhotic animals. We studied the effects of the histamine H1 blocker hydroxyzine in sleep alterations in patients with cirrhosis in a double-blind, randomized controlled fashion.

Methods: A total of 35 patients (age 56 yr [36-69], Pugh's score 9 [7-12], portosystemic shunt: N = 7) with minimal HE and long-standing sleep difficulties (8 months [4-48]) and free from benzodiazepines were randomized to hydroxyzine 25 mg at bedtime (N = 17) or placebo (N = 18) for a 10-day period. Measurements of sleep behavior using visual analog scale and wrist actigraphy, neuropsychological tests, and protein s100beta serum levels were performed at baseline and at day 10.

Results: Subjective improvement in sleep was observed in 40% of hydroxyzine-treated patients but in none receiving placebo (P < 0.04). Objectively, 65% of hydroxyzine-treated patients versus 25% of patients under placebo had a >or=30% increase in sleep efficiency as measured by wrist actigraphy (P < 0.04). Neuropsychological tests (Z scores) and protein s100beta levels remained statistically unchanged in both groups. One patient developed an acute episode of encephalopathy reversible upon cessation of hydroxyzine.

Conclusions: In contrast to placebo, hydroxyzine 25 mg at bedtime improved sleep behavior (subjectively and using wrist actigraphy) in patients with cirrhosis and minimal HE. The risk of precipitating overt HE warrants some caution when prescribing this drug.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Hepatic Encephalopathy / complications*
  • Histamine H1 Antagonists / therapeutic use*
  • Humans
  • Hydroxyzine / therapeutic use*
  • Liver Cirrhosis / complications*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Pilot Projects
  • Sleep Wake Disorders / drug therapy*
  • Sleep Wake Disorders / etiology
  • Statistics, Nonparametric
  • Treatment Outcome


  • Histamine H1 Antagonists
  • Hydroxyzine