Piche T et al. (2005) Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomized, double blind, placebo controlled study. Gut 54: 1169–1173

Researchers in France have found that a drug that nullifies the action of the neurotransmitter serotonin reduces fatigue in patients with chronic hepatitis C (CHC). Previous studies have hinted that central dysfunction has a role in the pathogenesis of fatigue, but few, if any, randomized, placebo-controlled trials have been conducted until now.

CHC patients experience a high prevalence of fatigue, characterized by a lessened capacity for work and a feeling of weariness and irritability. Hepatologists are therefore seeking to understand the multiple factors behind this phenomenon and to develop effective therapies to improve quality of life.

Piche et al. focused on ondansetron, a serotonin antagonist. They used a specially designed questionnaire that enabled them to quantify fatigue in a sample of 36 patients with CHC using a measure known as the Fatigue Impact Scale (FIS). They found that 4 weeks of twice-daily treatment with ondansetron (4 mg orally) not only reduced fatigue by 37.8%, but also had a positive effect on the incidence of depression.

Despite these positive results, the researchers raise concerns that the drug might not be cleared effectively by the liver in patients with CHC, since its effect was still evident 30 days after the treatment was stopped. Larger multicenter trials are necessary to assess further the efficacy and safety of this treatment.