OBJECTIVES: PERFORM (Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder) is a 2-year prospective observational cohort study conducted in Europe (France, Germany, Spain, Sweden and UK). Objectives are to describe the functioning of patients with major depressive disorder (MDD) and factors associated with functional impairment. Here we compare characteristics and outcomes of patients switching antidepressant treatment (ADT) with those initiating ADT at baseline, on an interim 1000-patient dataset. METHODS: Outpatients were recruited from primary or secondary care. Inclusion criteria were: DSM-IV-TR diagnosis of MDD, age 18-65 years, initiation or first switch to an ADT, in monotherapy. In addition to socio-demographics and disease history, data collection included clinician assessments (MADRS and CGI-S) and patient-rated scales evaluating depression (PHQ-9), functioning (SDS), work productivity (WPAI-SHP) and quality of life (QoL - EQ-5D). RESULTS: Of 947 analysable patients at inclusion, 213 (23%) patients were switching (76% for lack of efficacy), versus 716 (77%) initiating ADT. Switchers were slightly older (mean age 46 versus 43 years) and more often female (77% versus 72% women). Switching patients had more severe symptom profiles: more had previous depressive episodes (34% versus 24%) and previous suicide attempts (16% versus 12%). Severity of current episode was greater for switchers (46% versus 36% with a CGI-S score above “markedly ill”; 48% versus 38% with a PHQ-9 score above the severe depression threshold). MADRS scores were similar: 18.1 versus 17.6. QoL was poorer for switchers (EQ-5D: 0.449 versus 0.567), as was overall patient functioning (47% versus 36% with an SDS total score in the highest quartile), while no difference was found for absenteeism (35% versus 34%) and presenteeism (49% versus 50%) (WPAI-SHP). CONCLUSIONS: Patients switching ADT had more severe symptom profiles, lower quality of life and higher functional impairment, compared to non-switching patients.