The Early Medication Change (EMC) Trial

Inclusion Criteria: * Major Depressive Disorder (MDD), first episode or recurrent, according to DSM-IV * HAMD17 score of ≥18 pts. * Age between 18 and 65 years and age ≤ 60 years at the time of the first depressive episode * Ability of subject to understand character and individual consequences of clinical trial * Signed and dated informed consent of the subject must be available before start of any specific trial procedures. Exclusion Criteria: * Acute risk of suicide needing an intervention not comprised by protocol treatment (e.g. electroconvulsive therapy) * Patients with a lifetime DSM-IV diagnosis of dementia, schizophrenia, schizoaffective disorder, bipolar disorder * Patients with a current DSM-IV diagnosis of posttraumatic stress disorder, obsessive-compulsive disorder, anxiety disorder, or eating disorder and the requirement of a treatment not comprised by protocol treatment * Patients with DSM-IV substance dependency requiring acute detoxification * Depression due to organic brain disorder, e.g. Multiple Sclerosis and Parkinson's Disease * Women who are pregnant, breastfeeding or planning to become pregnant during the trial * Women who are not sterile by surgery or for more than two years postmenopausal or women with childbearing potential who not practicing a medically accepted contraception during trial * Patients currently taking antidepressant medication, which has been started within the 2-4 weeks prior to study begin and a continuation of this antidepressant medication is clinically indicated * A clear history of non-response to an adequate treatment trial in the current major depressive episode to any protocol antidepressant. A "clear history of non-response" has to be assumed, when the following criteria are fulfilled: * ad Escitalopram: Treatment with a mDDD ≥ 15 mg/d for 4 weeks or CPL 15-80 ng/ml for four weeks without response, i.e. a symptom reduction ≥ 50% between start and end of treatment. * ad Venlafaxine: Treatment with a mDDD ≥ 300 mg/d for 4 weeks or CPL 195-400 ng/ml for four weeks without response, i.e. a symptom reduction ≥ 50% between start and end of treatment; * ad Lithium: Treatment with CPL 0.6-0.8 mmol Li+ for four weeks without response, i.e. a symptom reduction ≥ 50% between start and end of treatment * History of medical or psychological condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or render the patient at high risk from treatment complications * History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product * Clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Such conditions may include gastrointestinal, cardiovascular, vascular disease, pulmonary/respiratory, hepatic impairment, renal, metabolic diseases, endocrinological, neurological, immune-deficiency, hematopoietic disease, or malignancies as determined by medical history, physical examination, or laboratory tests * Participation in other clinical trials during the present clinical trial or within the last 6 months * Medical or psychological condition that would not permit signing of informed consent