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Objective: To evaluate the comparative efficacy of 3 antidepressants, each representative of a distinct psychopharmacologic class, in the treatment of depressive disorders associated to Parkinson disease with dementia (PDD). Methods: A group of 23 patients, mean age 72.1, diagnosed with PDD for at least 2 years, who were admitted in our department for a major depressive episode (DSM IV TR), received antidepressant treatment with escitalopram (mean dose 15 mg daily, n=7), duloxetine (mean dose 45 mg daily, n=8) or trazodone (mean dose 150 mg daily, n=8). All patients received treatment for PDD with rivastigmine or donepezil continuously, for at least 12 months. The distribution of patients on the antidepressant treatment was randomized, in a single-blind manner. Patients were evaluated monthly, for 6 months, using Montgomery Asberg Depression Rating Scale, Hamilton Rating Scale for Depression- 17 items, Clinical Global Impression-Improvement and Mini Mental Status Examination. Results: Patients treated with duloxetine had the most significant improvement in the depressive symptoms, as the endpoint MADRS (-18.6+/-2.3, p< 0.01), HAMD (-13.2+/-1.1, p< 0.01) and CGI-I (- 3.2+/-0.5, p< 0.01) scores reflected. The differences between escitalopram and trazodone didn’t reach a significant level but, overall, both improved the depressive symptoms compared to baseline (p< 0.05). The difference between duloxetine and the other two antidepressants became significant after 8 weeks (p< 0.01). The severity of dementia symptoms didn’t vary significantly between the three groups at endpoint. Conclusion: Duloxetine had proven itself more efficient than escitalopram and trazodone in the improvement of the depressive symptoms in PDD. [Copyright &y& Elsevier]