The objective of this study is to evaluate the effectiveness of ketamine (infusion of 0.5mg/kg) and venlafaxine compared to the use of venlafaxine alone in the treatment of major depression (MADRS score ≥ 20 ) to six weeks of treatment.

Inclusion Criteria:

• Patients aged 18 or over,
• Introducing a single depressive episode or recurrent unipolar
• Responding to the diagnosis of severe major depressive episode according to DSM IV (Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition): MADRS score ≥ 20,
• absence of treatment with ketamine for analgesia or anesthesia during the last 6 months
• Affiliate (or beneficiary) to a social security system
• Informed consent signed

Exclusion Criteria:

• Contraindication to ketamine administration or treatment with venlafaxine;
• Failure of treatment with venlafaxine in the current episode (as low as 150 mg for 15 days);
• Axis I diagnosis according to DSM IV bipolar disorder (type I, II or III), schizoaffective disorder, schizophrenia, alcohol and other toxic or weaned for at least 6 months;
• Current Episode resistant stage V according to the classification of Thase and Rush (failed a course of bilateral ECT);
• Major depressive episode with severity criteria (significant risk of suicide is a MADRS score ≥ 5-SI; decubitus complications, intravenous hydration);
• episode currently being treated with fluoxetine;
• Patients hospitalized without their consent or measure of legal protection (guardianship, curatorship);
• Affection Organic likely to affect cognitive abilities and brain structures (eg, HIV, MS, lupus, Parkinson's disease, epilepsy, dementia ...) or decompensation;
• Pregnancy or breastfeeding underway.