Objective:The purpose of the present study was to evaluate the efficacy and safety of (-)-OSU6162 in doses up to 30 mg b.i.d. in patients suffering from mental fatigue following stroke or traumatic brain injury (TBI).Methods:This 4+4 weeks double blind randomised cross-over study included 30 patients afflicted with mental fatigue following a stroke or head trauma occurring at least twelve months earlier. Efficacy was assessed using the Mental Fatigue Scale (MFS), the Self-rating Scale for Affective Syndromes (CPRS), the Frenchay Activity Index (FAI), and a battery of neuropsychological tests. Safety was evaluated by recording spontaneously reported adverse events.Results:There were significant differences on the patients' total FAI scores (p=0.0097), the subscale FAI outdoor scores (p=0.0243), and on the trail making test (TMT-B) (p=0.0325) in favour of (-)-OSU6162 treatment. Principal component analysis showed a clear overall positive treatment effect in 10 of 28 patients; those who responded best to treatment had their greatest improvements on the MFS. Reported adverse events were mild or moderate in severity and did not differ between the (-)-OSU6162 and the placebo period.Conclusion:The most obvious beneficial effects of (-)-OSU6162 was on the patients' activity level, illustrated by the improvement on the FAI scale. Moreover, a subgroup of patients showed substantial improvements on the Mental Fatigue Scale. Based on these observed therapeutic effects, in conjunction with the good tolerability of (-)-OSU6162, this compound may offer promise for treating at least part of the symptomatology in patients suffering from stroke-or TBI-induced mental fatigue.