Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study

Abstract

Background and aims: There are no available effective therapies for fatigue associated with chronic hepatitis C (CHC). The serotonin antagonist ondansetron has been shown to be effective in the chronic fatigue syndrome. In this randomised, placebo controlled, double blind trial, we investigated the effect of orally administered ondansetron on fatigue in CHC. Methods: Thirty six patients with CHC were included if fatigue was their predominant symptom and they scored more than 4 on a visual analogue scale (0-10). During the study, fatigue and depression were measured on days 0, 15, 30, and 60 using a validated self report questionnaire (fatigue impact scale and Beck depression inventory). Patients were randomised to receive ondansetron tablets 4 mg twice daily or placebo for one month followed by an additional four weeks of observation. Results: Fatigue score was 85.4 (28.2) and 98.2 (26.9) in the ondansetron and placebo groups, respectively (NS). Ondansetron significantly reduced the fatigue score with more than 30% improvement on day 15 (57.1 (38.9); p,0.01), day 30 (54.5 (37.6); p,0.01), and day 60 (60.8 (37.3); p,0.01) whereas placebo did not. Overall, the reduction in fatigue was significantly higher with ondansetron compared with placebo (ANOVA for repeated measurements) for the whole follow up period (p = 0.03) or for the treatment period only (p = 0.04). Ondansetron also significantly reduced depression scores. Conclusions: The 5-hydroxytryptamine receptor type 3 antagonist ondansetron had a significant positive effect on fatigue in CHC. These observations support the concept that fatigue involves serotoninergic pathways and may encourage further evaluations of the efficacy of ondansetron on fatigue in chronic liver diseases.

Hepatitis C virus and neurological damage

“…Use of ondansetron which is a competitive antagonist of serotonin receptors has ameliorated fatigue in HCV infected patient. Also, the placebo controlled randomized study of thirty six HCV infected patients have shown an improved fatigue and depression scores with ondansetron [61] . These studies have shown an important role of serotoninergic pathway dysfunction that causes fatigue, reduced level of serum tryptophan, and a reduced synthesis of serotonin [62,63] .…”

Effect of Full-Dose Ondansetron on Tobacco Use among Male Alcohol- Dependent Outpatients - A Preliminary Study

“…Despite this, the reported side-effects between the placebo and ondansetron groups were not different. In addition, other studies on ondansetron efficacy in treating depressive and anxiety symptoms (concomitant to or even derived from other illnesses) have successfully tested doses between 8 and 24 mg daily, reporting a reduction in depressive symptoms [21,34], decrease of anxiety in subjects with Obsessive Compulsive Disorder [35], and even improvement on cognitive impairments among schizophrenics [36]. Also, 8 mg ondansetron (but not 4 mg) was shown to be useful for decreasing opiate withdrawal signs [37].…”

Ondansetron Augmentation of Serotonin Reuptake Inhibitors as a Treatment Strategy in Obsessive-Compulsive Disorder

“…4,5 It has been used as a treatment for tic disorders, 6 tardive dyskinesia, 7 and alcoholism. 8,9 It has also been successfully trialed in patients with tinnitus, 10 fatigue related to chronic hepatitis, 11 and opiaterelated pruritus, 12 but not benzodiazepine withdrawal. 13 Given that antipsychotic drugs can augment the benefits of SRIs in patients with OCD, might ondansetron carry similar benefits?…”