Resistance to psychoactive medications is a major problem in psychiatric clinical practice and a reason to treatment non-compliance.

Treatment resistant depression (TRD) is commonly defined as a failure to respond to two adequate trials with antidepressants (Burrows et al., 1994; Souery et al., 1999) in Major Depression, while treatment resistant Bipolar Depression has not been defined.

Conditions resulting in treatment resistance have not been clearly identified, similarly the ability to predict treatment resistance is under investigation. Resistance seems to be a misterious element in medical practice, and it is still nowadays a scientific challenge.

In this study we will try to answer to the “5W”, investigating some relevant factors among a population of inpatients, considerated treatment resistant according to the Thase and Rush criteria (1997) for Major Depression, and Pacchiarotti, Mazzarini and Colom criteria for Bipolar Depression (2009).

We will focus on diagnosis (PANSS, Hamilton Depression Rating Scale, Young Mania Rating Scale), anamnestic data (Child Trauma Questionnaire), pharmacological history, global functioning (GAF, CGI), personality traits and other symptoms (e.g., impulsivity, aggressivness, dissociative experiences) to detect risk and protective factors, and elaborate therapeutic and clinical strategies for the future.