Antidepressant effects of psilocybin in pharmaco-resistant depression

Prior treatment

• Metal implants from MR incompatible materials
• Regular use of medication that could interact with psilocybin (assessed by examining physician)
• Current use of monoamine oxidase inhibitors (MAOIs). Patients can be included if they will medications with an MAOI effect as part of tapering are completely stopped at least 14 days before V0.
• Previous experience with psilocybin, hallucinogenic mushrooms or ketamine is possible in maximum 10% of patients. This experience must not be within the last 12 months or within current derpestive episodes.
• Current medication with antidepressants, antipsychotics or other drugs with a direct antagonist effect on 5-HT2A receptors (e.g. trazodone, mirtazapine, mianserin, risperidone, quetiapine, ketanserin) or interruption of their use less than 7 days before administration of the study medication. Patients can be included, but these drugs must be completely discontinued as part of the tapering for at least 7 days before V0.
• Electroconvulsive therapy (ECT) in the previous 6 months
• Repetitive transcranial magnetic stimulation (rTMS) in the previous 4 weeks
• Current dependence on drugs or alcohol (ICD-10: F17.x) excluding tobacco and excluding abstinence lasting more than 2 years

Other illness

• Severe psychiatric comorbidity (axis I MINI, ICD-10 F0.X – F99.X with the exception of F32.1-2 or F33.1-2, the severity of the disease is clinically assessed by the examining physician)
• Condition after stroke, myocardial infarction in the last 6 months
• Heart failure
• Severe respiratory failure or acute respiratory depression
• History of convulsions
• Other serious somatic diseases or any other circumstance in which there would be a significant increase of blood pressure posed a serious threat to health (assessed by the examining physician)
• Allergy to components of medicinal products
• Intracranial hypertension, pulmonary hypertension, uncorrected arterial hypertension (BP > 150/100 mmHg)

Other

• Untreated or decompensated hyperthyroidism
• Glaucoma
• Pacemaker
• The current depressive phase is severe with psychotic symptoms (ICD-10: F32.2-3, F33.2-3)
• Daily use of benzodiazepine anxiolytics greater than the equivalent of 10 mg of diazepam
• MADRS suicidality score (item 10) > 4
• Suicide attempt in the last 6 months
• Duration of current depressive episode for more than 2 years
• Claustrophobia, inability to undergo MR examination
• Pregnancy or breastfeeding or plan to become pregnant within the next 3 months

• Men and women over the age of 18
• Diagnosis of moderate to severe depressive disorder without psychotic symptoms - ICD-10 criteria F32.1-2 or F33.1-2 and MADRS score ≥20
• The duration of the depressive episode is a minimum of 3 months and a maximum of 2 years
• treatment-resistant disease defined as: a) Failure of at least 2 and at most 4 adequate treatments (6 weeks of adequate therapeutic doses antidepressants, adequate non-pharmacological procedures, e.g. psychotherapy, neurostimulation treatment, phototherapy, etc.) within the current depressive episode, when using at least 2 antidepressants with a different pharmacological mechanism of action (augmentation is the gate as a second treatment) or in a combination of one pharmacological treatment and 1 non-pharmacological one treatment b) Intolerance of 2 different treatments and 1 adequate treatment or c) Intolerance of 3 different antidepressant treatments.
• Ability to understand and independently complete all protocol-defined examinations and scales and be present at all study visits
• Have a secured caregiver who will be able to be in personal contact with the patient 5 times a week
• Clinical trial participants of childbearing age must agree to use the prescribed methods contraception for the duration of the clinical trial: a) Women - Correct use of a highly reliable contraceptive method, i.e. combined hormonal contraception (in oral, vaginal or transdermal drug form), progestagen hormonal contraceptives associated with inhibition of ovulation (in oral or injectable pharmaceutical form), non-hormonal intrauterine device or intrauterine device releasing hormones, possibly the presence of bilateral tubal occlusion, vasectomy in the partner, or observing sexual abstinence. b) Men – Observing sexual abstinence or using an adequate contraceptive method (i.e. condom) in case of sexual intercourse.