Pruritus and fatigue associated with liver disease: is there a role for ondansetron?

Background: Complications of liver disease include pruritus and fatigue. Increased central opioidergic tone, which is modulated by serotoninergic pathways, contributes to the former; increased central serotoninergic tone may contribute to the latter. Objective: To examine non-clinical and clinical data relevant to the hypothesis that ondansetron, a 5-HT₃ receptor subtype antagonist, ameliorates pruritus and fatigue in liver disease. Methods: Non-clinical findings supporting the hypothesis are discussed and all trials of ondansetron for pruritus or fatigue in liver disease are reviewed. Conclusion: That ondansetron ameliorates pruritus in liver disease is strongly supported by subjective observations, but is not confirmed by objective findings in two controlled trials. Anecdotal observations also suggest that ondansetron ameliorates fatigue in liver disease, but in only one of two randomized controlled trials, that used subjective end points, is a similar conclusion possible.