Several studies have been conducted to evaluate personality characteristics in patients affected by major depressive disorder. Temperamental and character traits may help clinicians to identify responders to antidepressive therapy. The aim of our study was to evaluate these characteristics as possible predictive indices of response to SSRIs or SNRIs. A cohort of 41 patients was included (30 F and 11 M), whose diagnosis was made according to DSM-IV criteria. Subjects were interviewed using the HAM-D and the HAM-A scale in basal condition (T0) and after 4 weeks (T1) of antidepressive treatment. Patients with a ≥ 50% reduction of HAM-D and HAM-A score, have been considered as responders, when compared to basal conditions. All subjects were in monotherapy and evaluated using the TCI-R scale. In patients affected by major depressive disorder, personality assessment was characterised, from a temperamental point of view, by high levels of Persistence and Reward Dependence and, from a character one, by high levels of Self Directiveness and Cooperativity. After 4 weeks of antidepressive treatment, responders to HAM-D had higher levels of Responsibility versus Guilt, which could be considered as a predictor of positive response to SSRIs or SNRIs. Conversely, responders to HAM-A showed higher values of Responsibility versus Guilt and of Safety versus Fear of uncertainty. These values were predictive of a recovery of anxious sintomatology associated with depressive disorder. Our results are in line with those reported in the literature, indicating that character dimensions “Self Directiveness” and “Cooperativity” could be important predictors of response to antidepressants.