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

Study Overview
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Brief Summary
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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.

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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: ketamine venlafaxine
* Drug: Venlafaxine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine+venlafaxine<br>one injection of 0.5 mg/kg of kentamine the first day plus venlafaxine (150-375 mg day) during 6 weeks | Drug: ketamine venlafaxine<br>* After a washout period of 7 days of psychotropic medications with the exception of cyamemazine and hydroxyzine: Intravenous injection on day 0 to 0.5 mg / kg of ketamine D0 to D4: 75 mg of venlafaxine D4 to D14: 150 mg per day of venlafaxine D14 to D42: 150 mg daily of venlafaxine to 375 mg per day of venlafaxine if patient not responder<br>|
| Active Comparator: venlafaxine<br>venlafaxine (150-375 mg day) during 6 weeks | Drug: Venlafaxine<br>* After a washout period of 7 days of psychotropic medications with the exception of cyamemazine and hydroxyzine: Intravenous injection on day 0 to 0.5 mg / kg of placebo (saline serum) D0 to D4: 75 mg of venlafaxine D4 to D14: 150 mg per day of venlafaxine D14 to D42: 150 mg daily of venlafaxine to 375 mg per day of venlafaxine if patient not responder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive state | Assessment of depression by MADRS defining six weeks: the state of clinical response defined by a MADRS score less than 50% in MADRS score at baseline initial set. the state of clinical remission is defined by obtaining a MADRS score ≤ 8. | 6 weeks |