The Group for the Study of Resistant Depression (GSRD) (Souery et al., 2007, Journal of Clinical Psychiatry 68: 1062-1070), a collaborative project between eight centers in Belgium, France, Greece, Italy, Israel and Austria developed a staging model that distinguishes between ‘non-responders” (patients who fail to respond to one form of treatment, administered for six to eight weeks), a condition which is now termed ‘insufficient response” by the European Medicines Agency (EMA), ‘treatment resistant depression” (TRD, patients that fail to respond to two or more adequate antidepressant trials of different classes of antidepressants), and ‘chronic resistant depression” (CRD, patients being treated with several antidepressants for more than twelve months). The clinical findings of the GSRD provide a set of eleven variables associated with treatment response, among them comorbid anxiety disorders as well as melancholic features (Souery et al., 2007, Journal of Clinical Psychiatry 68: 1062-1070). Although there is a plethora of hints in textbooks that switching the mechanism of action should be obtained when a patient does not respond to one medication, the results of the GSRD challenge this notion by describing that staying on the same antidepressant mechanism of action for a longer time is more beneficial than switching (Souery et al., 2011; World Journal of Biological Psychiatry 12: 364375). The results of the GSRD European multicenter project has recently been summarized by Schosser et al. (European Neuropsychopharmacology; 2012; 22: 259-266). New data including machine learning techniques to handle the large amount of data obtained in this ongoing research protocol will be presented.