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The aim of this study was to assess the presence of demoralization and major depression in the setting of medical disease. 807 consecutive outpatients recruited from different medical settings (gastroenterology, cardiology, endocrinology, and oncology) were assessed according to DSM-IV criteria and Diagnostic Criteria for Psychosomatic Research, using semistructured research interviews. Demoralization was identified in 245 patients (30.4%), while major depression was present in 135 patients (16.7%). Even though there was a considerable overlap between the 2 diagnoses, 59 patients (43.7%) with major depression were not classified as demoralized, and 169 patients (69.0%) with demoralization did not satisfy the criteria for major depression. The findings suggest a high prevalence of demoralization in the medically ill and the feasibility of a differentiation between …