The serotonin receptor antagonist ondansetron (Zofran) reduces depression and fatigue in patients with chronic hepatitis C, French researchers report in the August 5th issue of Gut.
The fatigue associated with hepatitis C is believed to be associated with central dysfunction and altered opioid- and serotonin-mediated neuromodulation, Dr. T. Piche and colleagues observe. Because ondansetron has been shown to relieve fatigue in patients with chronic fatigue syndrome, the team theorized it would have similar clinical benefit in hepatitis C.Dr Piche of Hopital Archet, Nice and colleagues randomly assigned 18 patients to ondansetron 4 mg twice daily for 4 weeks and 18 to placebo. Fatigue was documented via the Fatigue Impact Scale questionnaire and depression with the Beck Depression Inventory (BDI). Ondansetron was associated with a 32.2% reduction in fatigue scores on day 15 and 37.8% on day 30. Corresponding reductions with placebo were 13.6% and 20.4%. Ondansetron continued to be associated with improvement on day 60 (31.5% reduction versus 5.8% reduction in the placebo group). Ondansetron was associated with significantly more relief of fatigue compared with placebo throughout the study period (p = 0.03).Findings were similar for depression, with 37.3%, 35.2% and 41.9% reductions in BDI scores in the ondansetron group and 17.3%, 20.4% and 5.8% in the placebo group on days 15, 30 and 60 (p > 0.05).Although puzzled by the prolonged effect of ondansetron beyond the treatment period, Dr. Piche and associates suggest that this effect could be related to sustained neuronal mechanisms, such as hippocampal neurogenesis. “Considering the negative impact of fatigue on quality of life and reduced adherence to antiviral therapy in infected patients,” the authors conclude, “it is crucial to further confirm these data in large multicentre trials.” In a related editorial, Dr. N. M Barnes, of the University of Birmingham comments that “Given the strong association of fatigue as a symptom of depressed patients, it would be pertinent to investigate whether the ondansetron-induced reduction in the two symptoms are interrelated.” (Source: Gut 2005;54:1169-1173: Reuters Health: Oncolink: July 2005.)