Inclusion Criteria:

• Meet DSM-IV criteria for primary diagnosis of MDD.
• HAM-D21 score of ≥ 16.
• 18-65 years age-range
• Subjects with English or Dutch literacy and fluency.
• Written, informed consent.

Exclusion Criteria:

• Presence of suicidal ideations/tendency (as determined by a score >= 8 in Section C of the MINI Plus, bipolar I-III, psychosis or primary eating disorders, post-traumatic Stress disorder, Obsessive Compulsive Disorder as well as any Axis II personality disorders.
• Pregnancy and women of child bearing potential who are not taking a medically accepted form of contraception and are at risk of becoming pregnant during the study.
• Breastfeeding.
• Known contra-indication to the use of Escitalopram, Sertraline or Venlafaxine XR as defined in the product package insert for each drug (including previous treatment failure at the highest recommended dose).
• Use of any antidepressant or CNS drug which can not be washed out prior to participation.
• Use of any medication which is known to be contraindicated with Escitalopram, Sertraline, or Venlafaxine XR (refer to the product package insert for each drug).
• Known medical condition, disease or neurological disorder which might, in the opinion of investigator/s, interfere with the assessments to be made in the study or put subjects at increased risk when exposed to optimal doses of the drug treatment (including, but not limited to, a cardiac rhythm disorder, prior myocardial infarction, angina, congestive heart failure, hypertension, stroke, active peptic ulcer, renal insufficiency, liver disease, neoplastic disease, inflammatory disease, diabetes, blood clotting disorder).
• Personal history of physical brain injury or blow to the head that resulted in loss of consciousness of greater than five minutes.
• Recent/current substance dependence.
• Participation in an investigational study within four months of the baseline visit (excluding follow-up studies in which the test drug/device has been registered in a major market) in which subjects have received an experimental drug/device that could affect the primary end points of this study.
• Subjects who, in the opinion of the investigator, have a severe impediment to vision, hearing and/or hand movement, which is likely to interfere with their ability to complete the testing batteries.
• Subjects who, in the opinion of the investigator, are unable and/or unlikely to comprehend and follow the study procedures and instructions.