Behavioural troubles due to frontotemporal dementia (FTD) are difficult to treat. The serotonergic system is associated with frontal lobes, the degeneration of which contributes to FTD. Trazodone increases the extracellular 5-HT levels in the frontal cortex. In a randomised, double-blind, placebo-controlled cross-over study, we investigated the effect of trazodone. There was a significant decrease in the Neuropsychiatry Inventory (NPI) total score with trazodone (p = 0.028) in the 26 evaluable patients. A decrease of more than 50% in the NPI score was observed in 10 patients with trazodone. This improvement was mainly based on the improvement of 4 items of the scale (irritability, agitation, depressive symptoms and eating disorders). The Mini-Mental State Examination was not modified and trazodone was well tolerated. Results of this first placebo-controlled trial suggest that trazodone is an effective treatment for the behavioural symptoms of FTD.