Ondansetron and pruritus in chronic liver disease: a controlled study

Increased central opioidergic neurotransmission, mediated by endogenous opioid peptide agonists, contributes to the pruritus of cholestasis. There are interrelationships between the opioid and serotonin neurotransmitter systems. The serotonin 5-HT3 receptor subtype antagonist, ondansetron, has been reported to ameliorate centrally-mediated pruritus induced by exogenously administered opiates. This study was designed to determine whether long-term oral administration of ondansetron is efficacious in ameliorating pruritus complicating chronic liver disease.

Seventeen patients with severe pruritus complicating established chronic liver disease were randomized to receive, double-blind, ondansetron (8 mg) or a placebo orally; each was administered thrice daily for a 4-week period. Endpoints were subjective scores of pruritus and objective 24-hour measurements of scratching activity. Analysable data were generated in 13 of the patients.

Ondansetron therapy was associated with ameliorations of pruritus that appeared to be clinically significant in 5 patients (38%); in these 5 patients the mean decrease in a subjective score of pruritus was 27% of the scale of the score. However, these apparent ameliorations were not associated with robust decreases in scratching activity. For the whole group of 13 patients mean scratching activity during ondansetron therapy was not significantly less than that during treatment with placebo (p = 0.19). The total time that patients were not scratching was similar during treatment with ondansetron and placebo (p = 0.57).

The findings suggest that serotoninergic neurotransmission, in neurons bearing receptors of the 5-HT3 subtype, plays no more than a minor role in the mediation of pruritus complicating chronic liver disease. The lack of an association between the results of applying subjective scores of pruritus and scratching activity emphasizes the need to include an objective quantitative efficacy endpoint in the design of trials of new therapies for pruritus.