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Background: Behavioral and psychological symptoms of dementia (BPSD) occur in up to 80% of Alzheimer’s disease (AD) patients and represent one of the most common reasons for early institutionalization and increase in management costs.; Objectives: This study evaluated the effects of four drugs (memantine, donepezil, rivastigmine, galantamine) in BPSD in AD patients.; Methods: This was a prospective, longitudinal, randomized, open-label, 4-arm, parallel-group, 12-month clinical trial carried out in 177 AD patients. The severity of BPSD was evaluated at baseline and after treatment with memantine (n = 48), donepezil (n = 42), rivastigmine (n = 46), and galantamine (n = 41), by using the Neuropsychiatric Inventory (NPI) and the Behavioural Pathology in Alzheimer’s Disease (BEHAVE-AD) scales.; Results: The NPI and BEHAVE-AD total scores improved from baseline to month 12 in all groups. The improvements in both scales were statistically significant in the memantine, donepezil, and rivastigmine groups, but not in the galantamine group. Responder analyses showed that treatment with memantine and rivastigmine resulted in more patients improving on NPI and BEHAVE-AD score, respectively. Agitation/aggression was the NPI item with the highest improvements (significantly versus baseline in the memantine and in the rivastigmine groups), while aggression and anxiety/phobias were the mostly improved BEHAVE-AD items (significantly in the rivastigmine group for both and in the rivastigmine group only for anxiety/phobias). All treatments were well tolerated: most of adverse events reported were transient and of mild-to-moderate intensity.; Conclusions: This study suggests that specific drugs for AD, especially memantine and rivastigmine, may be effective in the improvement of BPSD in patients with mild to moderate AD, without major side effects.;