| Summary: | Abstract Background Multiple sclerosis (MS) is a common neurological disorder with a variety of manifestations including fatigue. Fatigue may interfere with daily work and activities. Different pharmacological and non-pharmacological methods have been used for treatment of this symptom in MS patients. In this study, the effect of ondansetron and amantadine in the treatment of fatigue was compared. Methods In this randomized clinical trial, 53 MS patients with fatigability were enrolled (mean age ± standard deviation: 54.00 ± 7.88, Female/male ratio: 45/8). Patients were referred to Imam Clinic and Sina Hospital, Hamadan, Iran. Patients were assessed using the Fatigue Severity Scale (FSS) questionnaire. Patients were randomly assigned to either the amantadine or ondansetron treatment groups and received treatments in a crossover manner. The severity of fatigue was measured using FSS questionnaire in four stages (beginning and end of each regimen). Data were analyzed using SPSS software version 16. Results The mean and standard deviation of patients’ fatigue scores before treatment were 43.07 ± 10.36 and 43.22 ± 9.67 in the amantadine and ondansetron group, respectively. These scores were 37.36 ± 7.87 and 40.00 ± 8.94 after treatment in the amantadine and ondansetron group, respectively. Both drugs significantly decreased the fatigue severity of patients (P < 0.001). There was no statistically significant difference between two regimens in terms of the mean score of fatigue before and after treatment and the frequency of complications. However, when ranking the severity of fatigue (mild, moderate, severe), fatigue reduction after intervention in the amantadine group was significantly higher than ondansetron (P = 0.026). Conclusion Both amantadine and ondansetron reduce fatigue in MS patients, but the efficacy of amantadine in reducing the MS-associated fatigue is greater than that of ondansetron.
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