The EMC trial investigates for the first time prospectively whether Major Depression Disorder patients with non-improvement after 14 days of antidepressive treatment with EMC are more likely to become remitters compared to patients treated according to current guidelines, i.e., with a medication change after 28 days of treatment in case of non-response.

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