ABSTRACT— In a randomized general practice study, the prophylactice effect of femoxetive (a 5HT uptake inhibitor) was compared with placebo in migraine patients. Treatment, with separate randomization schedules in each practice, was allocated to 65 patients. Each patient was treated for 16 weeks with 200 mg increasing during the first nine days to 600 mg daily. No effect of femoxetine could be demonstrated in attack frequency and headache index. Separate analysis of maximum reduction in serotonin concentration during treatment revealed no difference in efficacy when compared with placebo. This supports earlier studies that femoxetine generally exerts no prophylactic effect on migraine, and the hypothesis that platelet 5HT might be of major importance in the pathogenesis of migraine is not supported.