1. Men and women at the age between 18 to 65 years, with dextromanual dominance. 2. Patients have to answer DSM IV criteria for the major depressive episode, without psychotic symptoms, on the clinical investigation basis, by Mini international neuropsychiatry interview. 3. Input score in MADRS Scale higher than 20, what matches medium severity of clinical state in CGI scale higher or equal with 4. 4. Mental ability to understand and sign informed consent. MedDRA version: 14.1 Level: PT Classif
Conditions
Interventions
Trade Name: CALYPSOL
Product Name: ketamine hydrochloride
Product Code: 05/140/97-C
Pharmaceutical Form: Infusion
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: I
Sponsors
Prague Psychiatric Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women at the age between 18 to 65 years, with dextromanual dominance, t.j. scores 100 in Edinburgh Handedness Inventory (EHI). 2. Patients have to answer DSM IV criteria for the major depressive episode, without psychotic symptoms, on the clinical investigation basis, by Mini international neuropsychiatry interview (M.I.N.I., Czech version 5.0.0.) - structured interview for psychiatric disorders on axis I based on DSM- IV. 3. Input score in MADRS (Montgomery-Asberg Depression Rating Scale) higher than 20, what matches medium severity of clinical state in CGI (ClinicalGlobal Impression ) scale higher or equal with 4. 4. Mental ability understand and sign informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Increased vulnerability to the development of psychosis ascertained on the basis a) M.I.N.I., b) family anamnesis of psychosis at relatives I. and II. degree. 2. Presence of another psychiatric disorder on axis I base on DSM- IV less than 6 months before inclusion to the study. 3. Contraindication for ketamine administration (hypertension, heart defect, severe cardiovascular disease, cerebrovascular accident in anamnesis, intracranial hypertension, glaucoma, hyperthyreosis, convulsions in anamnesis). 4. Using of drugs with strong anticholinergic efect. 5. Pregnant women, breastfeeding women or women without appropriate contraception. 6. Electroconvulsive treatment in the last 2 months before visit 1. 7. Treatment augmentation by lamotrigine, lithium, clozapine or IMAO (inhibitor of monoaminooxidase) in the last 2 weeks before visit 1. 8. Pharmaceuticals, illness and states, which may have influence on EEG (benzodiazepines, classical antipsychotics, head injury, encephalitis, epilepsy, etc.). 9. Clinically assessed serious suicidal risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of the trial is to answer the question whether the group of ketamine responders differs from ketamine non-responders: a) in the activation of mTOR, b) in the anatomical and functional parameters of the brain (before infusion), c) in the morphological and functional changes induced by ketamine.;Secondary Objective: The evaluation of the mTOR pathway in patients with depression could be predictor of the effectiveness of ketamine infusion.;Primary end point(s): The working hypothesis: H0A. mTOR activity after the ketamine infusion is not different compared to the activity after the placebo infusion. H0B. mTOR activity does not differ between responders and non-responders to ketamine (definition of response: = 50% reduction in MADRS score on at least one of the two assessments - 1st day after infusion or 4th day after infusion). H0C. The proportion of subjects with increased activity of mTOR does not differ between responders and non-responders.;Timepoint(s) of evaluation of this end point: The working hypothesis: H0A. mTOR activity two hours and 24 hours after the ketamine infusion is not different compared to the activity two hours and 24 hours after the placebo infusion. H0B. mTOR activity does not differ between responders and non-responders to ketamine two hours and 24 hours after the infusion (definition of response: = 50% reduction in MADRS score on at least one of the two assessments - 1st day after infusion or 4th day after infusion). H0C. The proportion of subjects with increased activity of mTOR does not differ between responders and non-responders two hours and 24 hours after the ketamine infusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): H0D. The changes in functional brain connectivity measured by eLORETA does not differ between responders and non-responders in ventromedial frontal cortex, including the orbitofrontal cortex and subgenual cingulate after the administration of single ketamine infusion.;Timepoint(s) of evaluation of this end point: H0D. The changes in functional brain connectivity measured by eLORETA does not differ between responders and non-responders in ventromedial frontal cortex, including the orbitofrontal cortex and subgenual cingulate, 30 min and 24 h after the administration of single ketamine infusion. | — |
Countries
Czech Republic
Contacts
Public Contactprincipal investigator
Prague Psychiatric Centre
Outcome results
None listed