Early efficacy of ketamine compared to placebo, in add-on therapy of venlafaxine for inpatients with severe unipolar major depressive episodes: a double blind randomized controlled trial

Prior treatment

• Participating in other interventional research involving the human body or within the exclusion period following previous research involving the human body, if applicable
• Contraindication to venlafaxine (hypersensitivity to venlafaxine or excipients, unstable hypertension, no indication for venlafaxine treatment in clinician's opinion due to ineffectiveness or tolerability of previous venlafaxine treatment).
• Current or previous treatment with venlafaxine or ketamine in the month prior to study inclusion
• Pregnant or breast-feeding patients (women of childbearing potential must have a negative urine or blood test for human chorionic gonadotropin prior to trial entry). Planned pregnancy within three months of enrolment

Other illness

• Criteria relating to associated pathologies entailing particular risks: pharmaco-resistant MDE (failure of at least two properly conducted treatments with two different antidepressant treatment classes), MDE with psychotic features, psychotic disorder, bipolar disorder, current (<1 month) substance use disorder (excluding tobacco

Lab values

• Liver impairment (AST and/or ALT > 3 ULN, PAL and/or GGT and/or bilirubin > 2 ULN)
• Severe renal insufficiency (GFR <30ml/min with Cockcroft's formula)
• Contraindication to ketamine : Hypersensitivity to active substance or excipients, comatose state, central nervous system (CNS) depression, Parkinson's disease, Lewy body dementia, progressive supranuclear palsy, known prolongation of the QTc interval (>450ms for men and >470ms for women) or congenital long QT syndrome, recent acute myocardial infarction, uncompensated heart failure, history of ventricular arrhythmias or torsades de pointes, uncorrected hypokalemia (K+ < 3. 5 mmol/l), epilepsy, uncontrolled hypertension, porphyria.

Other

• Social insurance
• Need to maintain another antidepressant, MAOI, Millepertuis or benzodiazepines (cyamemazine is permitted)
• Adult under guardianship, curatorship, or safeguard of justice

• Current MDE in the context of Major Depressive Disorder (DSM-5 criteria), hospitalized (open care) for this episode, with a minimum HDRS score of 24 and in the context of an indication for the introduction of venlafaxine treatment.
• Patient aged between 18 and 65
• Signed free and informed consent
• Membership of a social security scheme
• For women of childbearing age, effective contraception throughout study participation