The study will include 60 patients with pharmaco-resistant depression (30 male, 30 female, aged 18–65). The basic inclusion criterion is the diagnosis of pharmaco-resistant moderate to severe depressive episode (F32.1–2, F33.1–2) without psychotic symptoms as per ICD-10 criteria with a MADRS score over 20 and excluding patinets with MADRS suicidality score (item 10) more than 4.
Conditions
Sponsors
Národní ústav duševního zdraví
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Men and women aged 18-65 2) Diagnosis of moderate to severe depressive disorder without psychotic symptoms - ICD-10 criteria F32.1-2 or F33.1-2 and at the same time MADRS score > 20 3) The duration of the current depressive epizode is at least 3 months and maximum 2 years 4) Treatement-resistant depression defined as: a) Failure of at least 2 and at most 4 adequate treatments (6 weeks of full therapeutic dose of antidepressant, adequate non-pharmacological treatemment - eg psychotherapy, neurostimulation treatment, phototherapy, etc.) within the current depressive episode, using at least 2 types of antidepressants with different pharmacological mechanisms of action (augmentation is taken as a second treatment) or b) Intolerance of 2 different treatments and 1 adequate treatment or c) Intolerance of 3 different antidepressant treatments. 5) Ability to understand the study protocol and to be able to complete all study visits and examinations as defined per protocol. 5) Participants in a clinical trial of childbearing potential must agree to the use of prescribed contraceptive methods for the duration of the study: a) Women - Proper use of a highly reliable method of contraception, ie combined hormonal contraceptives (oral, vaginal or transdermal dosage form), gestagen hormonal contraceptives associated with ovulation inhibition (oral or injectable dosage form), non-hormonal intrauterine device or intrauterine device releasing hormones, ev. the presence of bilateral tubal occlusion, a partner's vasectomy, or adherence to sexual abstinence. b) Men - Adherence to sexual abstinence or the use of an adequate contraceptive method (ie condom) in case of sexual intercourse. Periodic abstinence is not considered an acceptable method. The clinician, together with the volunteer, chooses the most appropriate method of contraception. The chosen method of contraception will be documented in the screening visit. 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 60 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Serious psychiatric comorbidity (axis I MINI, ICD-10 F0.X - F99.X, the intensity of the disorder will be clinically assessed by the study clinician) 2) The current depressive phase is severe with psychotic symptoms (ICD-10: F32.3, F33.3) 3) MADRS suicidality score (item 10)> 4 4) Suicideal attempt within last 6 months 5) Duration of the current depressive episode longer than 2 years 6) Current drug or alcohol dependence (ICD-10: F17.x) with the exception of tobacco and with the exception of abstinence lasting more than 2 years 7) Claustrophobia, inability to undergo MR examination 8) Pregnancy or breast-feeding or plan to become pregnant within the next 3 months 9) Intracranial hypertension, pulmonary hypertension, uncorrected arterial hypertension (BP> 150/100 mmHg) 10) Condition after stroke, myocardial infarction in the last 6 months 11) Heart failure 12) Untreated or decompensated hyperthyroidism 13) Glaucoma 14) Severe respiratory failure or acute respiratory depression 15) History of seizures 16) Other serious somatic disease or any other circumstance in which a significant increase in blood pressure would pose a serious threat to health (to be assessed by the study clinician) 17) Pacemaker 18) Metal implants made of MR incompatible materials 19) Regular use of medication that could interact with psilocybin (to be assessed by the investigator) 20) Current use of monoamine oxidase inhibitors (MAOIs). Patients can be enrolled if the IMAO treatment will be completely discontinued during tapering at least 14 days prior V0 21) Previous experience with psilocybin, hallucinogenic mushrooms or ketamine is possible in a maximum of 10% of patients. This experience must not be during the last 12 months or during the current depressive episode. 22) Recent use of antidepressants, antipsychotcis or other drugs with a direct antagonistic effect on 5-HT2A receptors (eg trazodone, mirtazapine, mianserin, risperidone, quetiapine, ketanserine) or discontinuation of their use for less than 7 days before dosing with study medication. Patients can be enrolled, but these drugs must be completeley tapered at least 7 days prior V0. 23) Electroconvulsive therapy in the previous 3 months 24) Daily use of benzodiazepine anxiolytics higher than the equivalent of 10 mg diazepam 25) Allergy to any of the components of study drugs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Evaluation of fast antidepressant effects of psilocybin versus ketamine.;Timepoint(s) of evaluation of this end point: 24 h after dosing of the study drugs.;Main Objective: Evaluation of the rapid antidepressant effect of psilocybin 25 mg compared to ketamine 250 mg using the MADRS scale completed 24 hours after a single dose of the drug. We assume that after 24 hours psilocybin 25 mg and ketamine 250 mg will have a similar antidepressant effect (decrease in depressive symptoms according to the MADRS scale) and at the same time the effect of both substances will be more pronounced compared to antidepressant-inactive midazolam 5 mg.;Secondary Objective: 1) Comparison of the duration of the antidepressant effect of psilocybin versus ketamine and midazolam during inpatient stay, ie. 3, 7 and 14 days after administration using the MADRS scale. 2) Comparison of the duration of the antidepressant effect of psilocybin compared to ketamine and midazolam 3, 4, 5, 6, 8 and 12 weeks after administration using the MADRS scale. 3) Comparison of the antidepressant effect of a single application of psilocybin, ketamine and midazolam after 24 h, 1, 2, 3, 4, 5, 6, 8 and 12 weeks from the application according to patient´s subjective evaluation - QIDS scale. 4) Comparison of response rates (50% reduction on the MADRS scale) and remissions (MADRS = 10) with psilocybin, ketamine and midazolam 24 hours, 1, 2, 3, 4, 5, 6, 8 and 12 weeks after administration. 5) Comparison of the time to return of depressive symptoms within 12 weeks (3 months) after a single application of psilocybin, ketamine and midazolam. 6) Safety profile of study medication | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Duration of the antidepressant effect of psilocybin, ketamine and midazolam using the MADRS scale during 2 weeks of inpatient stay 2) Duration of the antidepressant effect of psilocybin, ketamine and midazolam after termination of inpatient stay using the MADRS scale. 3) Duration of the antidepressant effect of a single application of psilocybin, ketamine and midazolam using the QIDS scale. 4) Comparison of response rates (50% reduction in MADRS scale) and remissions (MADRS = 10) following psilocybin, ketamine and midazolam treatment 5) Time to reoccurrence of the depressive symptoms within 12 weeks (3 months) after treatment with psilocybin, ketamine and midazolam. 6) Safety profile of study drug: a) acute (vital signs (BP/HR), BPRS, psilocin levels) b) longterm (BPRS, PSQ a Persistent effects scale);Timepoint(s) of evaluation of this end point: 1) 3 , 7 and 14 days during inpatient stay after dosing session 2) 3, 4, 5, 6, 8 and 12 weeks after dosing session 3) 24 h, 3, 7 and 14 days, 3, 4, 5, 6, 8 and 12 weeks after dosing session 4) 24 h, 3, 7 and 14 days, 3, 4, 5, 6, 8, and 12 weeks after dosing session 5) within 8 weeks (2 months) after dosing session 6) a) during treatment session with study drugs b) 24 h, 3, 7 and 14 days, 3, 4, 5, 6, 8 and 12 weeks after dosing session | — |
Countries
Czech Republic
Contacts
Public ContactRP6 Brain Electrophysiology
Národní ústav duševního zdraví
Outcome results
None listed