Patients with cardiovascular diseases necessitate a specific role of pharmacotherapy with regard to efficiency as well as side-effect profile. Whereas most of the antidepressants can be viewed as effective, the older ones, specifically the tricyclic or tetracyclic antidepressants have cardiovascular side-effects and therefore do not pose an option for this group of patients. With the introduction of the selective serotonin-reuptake-inhibitors (SSRIs) or serotonin-noradrenalin-reuptake-inhibitors (SNRIs) a new era for the treatment of depression with cardiovascular diseases emerged. In large epidemiological surveys it is documented that for cardiovascular problems like heart attack, the administration of antidepressants is of crucial role and decreases mortality. On the other hand, it emerged recently that some of the antidepressants might cause problems with regard to a possible QTC-prolongation. In a large European drug surveillance project we evaluated the cardiological changes during antidepressant treatment with SSRIs compared to other classes of antidepressants. The results of this analysis indicate that the group of SSRIs do not show any increased incidence of QTC interval prolongation compared to other antidepressants. Furthermore, these clinical data confirm that severe cardiological side-effects such as QTC interval prolongation arise more likely during the treatment with tricyclic antidepressants. From our study we conclude that the restrictions and prescriptions of SSRIs stated by the FDA and EMA should be reconsidered.