The objective of this re-analysis of the European Genome-Based Therapeutic Drugs for Depression Study (GENDEP) was to psychometrically test the unidimensionality of the full Montgomery Åsberg Depression Rating Scale (MADRS10) and the Hamilton Depression Scale (HAM-D17) versus their respective subscales (MADRS5 and HAM-D6) containing the core symptoms of depression severity. Rasch analysis was applied using RUMM 2030 software to assess the overall fit for unidimensionality. Neither the MADRS10 nor the HAM-D17 was found to fit the Rasch model for unidimensionality. The HAM-D6 (containing the items of depressed mood, guilt, work and interests, psychomotor retardation, psychic anxiety, and somatic general) as well as the analogue MADRS5 were tested for unidimensionality by use of the RUMM 2030 programme, and only the HAM-D6 was accepted. When testing for invariance across rating weeks or centres, the RUMM 2030 had to be supplemented with the Friedman two-way analysis of variance by ranks. The HAM-D6 but not the MADRS5 was accepted. It was therefore concluded that the HAM-D6 is a psychometrically valid outcome scale to measure change in clinical trials of antidepressants.