Spahr L et al. (2007) Histamine H1 blocker hydroxyzine improves sleep in patients with cirrhosis and minimal hepatic encephalopathy: a randomized controlled pilot trial. Am J Gastroenterol 102: 744–753

Patients with cirrhosis and minimal hepatic encephalopathy often experience sleep difficulties, but treatment with benzodiazepines is frequently ineffective and can have serious side effects. Dysregulated histaminergic neurotransmission has been associated with sleepiness through alterations in sleep–wake cycles in these patients; interestingly, regulation of these cycles has been shown to be partially restored by histamine H1 blockers in animal models of cirrhosis. In a double-blind, randomized, controlled trial, therefore, Spahr et al. investigated the potential of the histamine H1 blocker hydroxyzine to improve sleep in patients with cirrhosis and minimal hepatic encephalopathy.

All 35 patients (mean age 56 years [range 36–69 years]) studied had biopsy-proven cirrhosis (mean Pugh's score 9 [range 7–12]) and long-standing sleep difficulties. Exclusion factors were depression, active alcohol consumption or benzodiazepine use. Patients were randomly assigned hydroxyzine 25 mg at bedtime (n = 17) or placebo (n = 18). Sleep quality was assessed at baseline and at 10 days. Forty percent of hydroxyzine-treated patients indicated improved sleep quality in subjective neuropsychological tests, compared with no patients in the placebo group. Actigraphy showed a fall in night-time activity, leading to increased sleep efficiency in 65% of hydroxyzine-treated patients, compared with only 25% of patients in the placebo group.

The authors conclude that hydroxyzine treatment improved sleep in patients with cirrhosis and minimal hepatic encephalopathy, but recommend caution as treatment with histamine H1 blockers carries a risk for the development of overt hepatic encephalopathy.