psilocybine for Major depression | Treatment-resistant depression

Inclusion criteria

• {"criterion_text":"- Men and women over the age of 18\n- Diagnosis of moderate to severe depressive disorder without psychotic symptoms - ICD-10 criteria F32.1-2 or F33.1-2 and MADRS score ≥20\n- The duration of the depressive episode is a minimum of 3 months and a maximum of 2 years\n- 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.\n- Ability to understand and independently complete all protocol-defined examinations and scales and be present at all study visits\n- Have a secured caregiver who will be able to be in personal contact with the patient 5 times a week\n- 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."}

Exclusion criteria

• {"criterion_text":"- 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)\n- Condition after stroke, myocardial infarction in the last 6 months\n- Heart failure\n- Untreated or decompensated hyperthyroidism\n- Glaucoma\n- Severe respiratory failure or acute respiratory depression\n- History of convulsions\n- 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)\n- Pacemaker\n- Metal implants from MR incompatible materials\n- Regular use of medication that could interact with psilocybin (assessed by examining physician)\n- The current depressive phase is severe with psychotic symptoms (ICD-10: F32.2-3, F33.2-3)\n- 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.\n- 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.\n- 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.\n- Electroconvulsive therapy (ECT) in the previous 6 months\n- Repetitive transcranial magnetic stimulation (rTMS) in the previous 4 weeks\n- Daily use of benzodiazepine anxiolytics greater than the equivalent of 10 mg of diazepam\n- Allergy to components of medicinal products\n- MADRS suicidality score (item 10) > 4\n- Suicide attempt in the last 6 months\n- Duration of current depressive episode for more than 2 years\n- Current dependence on drugs or alcohol (ICD-10: F17.x) excluding tobacco and excluding abstinence lasting more than 2 years\n- Claustrophobia, inability to undergo MR examination\n- Pregnancy or breastfeeding or plan to become pregnant within the next 3 months\n- Intracranial hypertension, pulmonary hypertension, uncorrected arterial hypertension (BP > 150/100 mmHg)"}

Primary endpoints

• {"endpoint_text":"- Evaluation of fast antidepressant effects of psilocybin versus ketamine.","definition_or_measurement_approach":"Primary measurement: verify rapid antidepressant effect of psilocybin 25 mg compared with ketamine 250 mg using the MADRS scale completed 24 hours after a single application of the study medication."}

Secondary endpoints

• {"endpoint_text":"- Duration of the antidepressant effect of psilocybin, ketamine and midazolam using the MADRS scale during 2 weeks of inpatient stay","definition_or_measurement_approach":"MADRS scale assessment during the first two weeks (inpatient days) to evaluate duration."}
• {"endpoint_text":"- Duration of the antidepressant effect of psilocybin, ketamine and midazolam after termination of inpatient stay using the MADRS scale.","definition_or_measurement_approach":"MADRS assessments after discharge at defined timepoints to evaluate duration post-hospitalization."}
• {"endpoint_text":"- Duration of the antidepressant effect of a single application of psilocybin, ketamine and midazolam using the QIDS scale.","definition_or_measurement_approach":"QIDS self-reported scale at multiple timepoints to assess duration of effect after single administration."}
• {"endpoint_text":"- Comparison of response rates (50% reduction in MADRS scale) and remissions (MADRS ≤ 10) following psilocybin, ketamine and midazolam treatment","definition_or_measurement_approach":"Response defined as ≥50% reduction in MADRS; remission defined as MADRS ≤10 at specified post-treatment timepoints."}
• {"endpoint_text":"- Time to reoccurrence of the depressive symptoms within 12 weeks (3 months) after treatment with psilocybin, ketamine and midazolam.","definition_or_measurement_approach":"Time-to-event analysis for return of depressive symptoms during 12-week follow-up period as defined in protocol."}
• {"endpoint_text":"- Safety profile of study drug: a) acute (vital signs (BP/HR), BPRS, psilocin levels) b) longterm (BPRS, PSQ a Persistent effects scale)","definition_or_measurement_approach":"Safety measured acutely via vital signs (blood pressure/heart rate), BPRS, psilocin plasma levels; long-term safety via BPRS, PSQ and Persistent effects scale."}

Methods

• Information on clinical trial website (Informacni web klinickeho hodnoceni PSIKET) — target: potential participants in Czechia
• Referral information leaflet for referring physicians (Informacni letak pro referujici lekare) — target: psychiatrists/physicians in Czechia
• Advertisement in psychiatry newsletter (Inzerat pro zpravodaj psychiatrie) — target: psychiatric professionals/readers in Czechia
• Facebook recruitment post (naborovy prispevek FB) — digital channel targeting potential participants in Czechia
• Printed flyers and posters (psiket_letak ruzovy, psiket_letak hnedy, psiketA2_plakat) — local outreach in Czechia
• Invitation to consultation day for people with depression (Pozvanka na konzultacni den pro lidi s depresi) — community engagement event in Czechia

Czechia

Earliest CTIS Part Ii Submission Date

04-11-2024

Latest Decision Or Authorization Date

03-11-2025

Processing Time Days

364

Number Of Sites

1

Number Of Participants

60

Primary sponsor

Full Name

Narodni Ustav Dusevniho Zdravi

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Czechia

Third parties

• {"country":"Czechia","full_name":"Masarykova Univerzita","duties_or_roles":"codes: 10,12,14,6,7","organisation_type":"Educational Institution"}