Study objective:Population based study to determine the clinical consequences and economic impact of using escitalopram (ESC) vs. citalopram (CIT) and venlafaxine (VEN) in patients who initiate treatment for a new episode of major depression (MD) in real life conditions of outpatient practice.Methods:Observational, multicenter, retrospective study conducted using computerized medical records (administrative databases) of patients treated in six primary care centers and two hospitals between January 2003 and March 2007. Study population: patients >20 years of age diagnosed with a new episode of MD who initiate treatment with ESC, CIT or VEN who had not received any antidepressant treatment within the previous 6 months, and were followed for 18 months or more. Main variables: socio-demographic variables, remission (defined as a patient completing 6 months of therapy), comorbidity, annual health care costs (medical visits, diagnostic and therapeutic tests, hospitalizations, emergency room and psychoactive drugs prescribed) and non-health care costs (productivity losses at work, mainly sick leave and disability). Statistical analyses: logistic regression and ANCOVA models.Results:A total of 965 patients (ESC = 131; CIT = 491; VEN = 343) were identified and met study criteria. ESC-treated patients were younger, with a higher proportion of males, and had a lower specific comorbidity (p < 0.01). ESC-treated patients achieved higher remission rates compared to CIT (58.0% vs. 38.3%) or VEN patients (32.4%), p < 0.001, and had lower productivity work losses compared to VEN patients (32.7 vs. 43.8 days), p = 0.042. No differences in productivity work losses were observed between ESC and CIT patients. Compared to the ESC group, higher costs in average/unit of psychoactive drugs were found in the VEN group (€643.00), p = 0.003, whereas no differences were observed between the ESC and CIT groups (€294.70 vs. €265.20). In the corrected model, total costs (health care and non-health care cost) were lower with ESC (€2276.20) compared to CIT (€3093.80), p = 0.047 and VEN (€3801.20), p = 0.045.Conclusions:ESC appears to be dominant in the treatment of new MD episodes when compared to CIT and VEN, resulting in higher remission rates and lower total costs.