A study examines the efficiency and safety of an anti-nausea drug as a treatment for fatigue in primary biliary cirrhosis
Fatigue affects up to 85 percent of patients with primary biliary cirrhosis (PBC), interfering with their quality of life and limiting their activities. Although several drugs have previously been studied, none have proven effective and there is currently no known treatment for it.
In a study led by Jeremy J. Theal, M.D. of the University of Toronto and published in the June 2005 issue of Hepatology, researchers examined the effects of ondansetron (an anti-nausea drug commonly used to treat nausea during chemotherapy) on fatigue associated with PBC, an inflammation of the bile ducts in the liver that leads to cirrhosis. Fatigue is often associated with depression, which may be caused by abnormalities in serotonin transmission; ondansetron helps regulate serotonin levels, which suggests its potential as a treatment for fatigue and depression.
Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons, Inc. is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.
A total of 54 patients from three Canadian centers (Toronto, Montreal, and Calgary) were included in a randomized, double blind placebo-controlled crossover trial, in which they received the drug in one four week period and a placebo in the other. The crossover design was chosen because fatigue is a subjective symptom and taking both the drug and the placebo in two separate blinded periods allowed patients to serve as their own controls. In addition to a diagnosis of PBC, patients had to score at least a 4 on the Fatigue Survey Score survey (FSS), a scoring system used to evaluate fatigue in patients with PBC. Patients received either a placebo in period 1 and ondansetron in period 2 or vice versa, but did not know which group they were in.
Patients taking ondansetron in period 1 showed the same decrease in fatigue as those taking a placebo. In period 2, patients taking the drug showed a decrease in fatigue, while those taking the placebo did not. However, since constipation is a major side effect of ondansetron and patients were informed of possible side effects before the trial began, those suffering from constipation most likely realized they were taking the drug, which may have influenced how they perceived their fatigue. For this reason, the researchers judged the results of period 2 to be invalid and used only the results from period 1 to evaluate the effects of ondansetron. They conclude that "ondansetron did not have a fatigue-reduction benefit greater than the considerable placebo effect we observed." In addition, neither depression nor sleep quality changed significantly on ondansetron versus the placebo.
The researchers point out that fatigue is difficult to measure and evaluate as it is a symptom that patients verbally report. "Thus in this study, the inherent difficulty in measuring a symptom as subjective and ill-defined as fatigue, particularly with questionnaires that are surrogate measures for this symptom, must temper any interpretations of clinical significance from fatigue changes that were measured," they state. They suggest that other drugs targeting the central nervous system may prove effective in combating fatigue associated with PBC, but that medications with fewer side effects should be tested in the future.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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