Estimate the Efficiency of the Association of an Injection of Ketamine and the Venlafaxine in the Severe Major Depressive Disorder for Six Weeks

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.