Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatigue is common in primary biliary cirrhosis (PBC). Altered central serotonergic neurotransmission may be involved in its pathogenesis. This multicenter, randomized, double-blind, placebo-controlled, crossover trial evaluated the efficacy of ondansetron, a selective 5-HT3 receptor subtype antagonist, for treating fatigue in PBC. A crossover design was chosen, allowing subjects to serve as their own controls-appropriate to evaluate fatigue, a subjective symptom. Sixty patients with clinically stable PBC, a Fatigue Severity Score (FSS) > 4, and no other identifiable cause for fatigue were enrolled. Subjects were randomized to receive ondansetron (4 mg) or placebo orally 3 times daily for 4 weeks (period 1). Subjects then crossed over, after a minimum 1-week washout period, for a further 4 weeks of ondansetron or placebo (period 2). Fatigue was measured at the beginning and end of each period by using the FSS and Fatigue Impact Scale (FIS). Six patients withdrew; the remaining 54 subjects had a mean baseline FSS of 5.55 (+/-0.1). Response to study medication in period 1 versus period 2 was not uniform; thus, it was necessary to analyze the trial periods separately. In period 1, there was no significant additional fatigue reduction on ondansetron over placebo. During period 2, FSS and FIS decreased significantly on ondansetron versus placebo (P = .001). However, period 2 results were invalidated because drug side effects unblinded subjects (constipation affected 63.0% of patients taking ondansetron, versus 13.3% on placebo). In conclusion, ondansetron administration did not confer clinically significant fatigue reduction when compared with placebo in our study population.
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PMID:A randomized, controlled crossover trial of ondansetron in patients with primary biliary cirrhosis and fatigue. 1591 60

Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagonist, specifically the 5-HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in patients with chronic liver disease. However, the results of a randomized controlled trial of ondansetron for fatigue in patients with primary biliary cirrhosis did not indicate that ondansetron was either effective or ineffective. The reasons for the uncertain outcome of the randomized controlled trial are not clear. One contributing factor may have been the use of subjective indices of fatigue as primary efficacy endpoints. There is a need to develop objective quantitative primary efficacy endpoints for use in trials of therapy for fatigue. Another contributing factor may relate to the conduct of a randomized controlled trial not invariably being the optimal approach to resolve a specific clinical issue, particularly when the application of statistical methods yields equivocal findings. When the results of a randomized controlled trial are indecisive, findings based on clinical judgement, medicine's most important asset, should be carefully evaluated.
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PMID:Personal view: a potential novel treatment for fatigue complicating chronic liver disease--how should its efficacy be evaluated? 1661 Dec 71