Comparison of the effect of aspirin and amantadine for the treatment of fatigue in multiple sclerosis: a randomized, blinded, crossover study Vahid Shaygannejad 1 , Mohsen Janghorbani 2 , Fereshteh Ashtari 1 , Hasanali Zakeri 1 1 Department of Neurology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran, 2 Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran Objectives: The purpose of this study was to compare the relative efficacy of acetylsalicylic acid (ASA) and amantadine for the treatment of fatigue in multiple sclerosis (MS). Methods: A 10-week, randomized double-blind crossover clinical trial conducted from October 2009 to September 2010. Fifty-two patients with MS presenting fatigue at 21 to 53 years of age were randomly allocated to the two treatment groups. The first group received amantadine (100 mg twice daily) for a total of 4 weeks. The second group received ASA (500 mg once daily) for four weeks. After a 2-week washout period, they crossed over to the alternative treatment for 4 weeks. Patients were rated at baseline and the end of each phase with the Fatigue Severity Scale (FSS). Results: ASA appeared to be equivalent in efficacy and safety to amantadine. A significant decrease in FSS occurred in both groups. Of the 26 patients treated with amantadine, the mean (SD) of FSS decreased from 4.8 (1.4) to 4.0 (1.4) (P,0.001). In the 26 patients treated with ASA, the mean (SD) of FSS decreased from 4.6 (1.4) to 3.5 (1.5) (P,0.001). Discussion: This study demonstrates that both ASA and amantadine significantly reduce MS-related fatigue. Both ASA and amantadine have previously been shown to reduce fatigue, and we postulate that treatment with ASA and amantadine may have similar benefits. Keywords: Aspirin, Amantadine, Fatigue, Multiple sclerosis, Treatment Introduction Fatigue is a most prevalent and disabling symptom in multiple sclerosis (MS), with a prevalence of more than 70% during the course of the disease. 1,2 It is often associated with significant disability and impaired quality of life, adversely affecting daily activity and work-related productivity for many patients. Fatigue management can improve care and treatment out- comes; therefore the management of fatigue in patients with MS is an important goal. The drugs used most frequently for fatigue management are amantadine, premoline, aminopyr- idines, and modafinil, all of which have central nervous system stimulant properties. 3–8 These drugs have limited efficacy and provide little insight into the pathogenesis of fatigue, and more effective agents are needed. 9 Modafinil has been shown to be effective in some studies, 7–12 and amantadine is an alternative for patients who do not respond to or cannot tolerate modafinil. Several short-term studies show that fatigue is reduced by amantadine treatment in patients with MS who have mild to moderate disability. 3,13–15 To the best of our knowledge, aspirin [acetylsalicylic acid (ASA)] has been tested only in one small trial for fatigue treatment in MS, 16 and the results suggested that ASA may be effective for MS- related fatigue owing to its antipyretic effect. No studies have compared amantadine with ASA for the treatment of MS-related fatigue. In the present randomized, double-blinded cross- over trial we compared the effects of amantadine and ASA to investigate which was more efficacious in the treatment of MS-related fatigue. Patients and Methods We used a 10-week piloted randomized, double- blinded crossover trial to compare the effect of ASA Correspondence to: M. Janghorbani, Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran. Email janghorbani@ hlth.mui.ac.ir 854 ß W. S. Maney & Son Ltd 2012 DOI 10.1179/1743132812Y.0000000081 Neurological Research 2012 VOL. 34 NO.9