Major depressive disorder is currently the fourth largest contributor to the worldwide burden of disease. Direct and indirect costs associated with depression place a significant burden on the health care system and society. Despite the development of new antidepressant medications, the management of patients with depression remains a therapeutic challenge. Obtaining a response in antidepressant therapy-commonly defined in clinical trials as an improvement of >erotonergic and noradrenergic neurotransmission, will increase the likelihood of remission.