Treatment-Resistant Depressive Episode or Treatment-Resistant Recurrent Depressive Disorder of moderate to severe degree withoutpsychotic features
Conditions
Interventions
Product Name: Psilocybin 25 mg
Product Code: Psilocybin25
Pharmaceutical Form: Capsule
INN or Proposed INN: Psilocybin
CAS Number: 520-52-5
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Central Institute of Mental Health
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) 25 to 65 years of age 2) Diagnosis of major depressive disorder (single and recurrent episodes) of moderate to severe degree (HAM-D score = 17) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) without psychotic features. Included ICD-10 diagnoses are F32.1, F32.2, F33.1, F33.2. a. If single episode, duration must be = 3 months. 3) Patients must meet criteria for treatment-resistance, defined as a. no adequate improvement despite two adequate courses of antidepressant treatment (6 weeks each, minimum) of different pharmacological classes in the current depressive episode. Augmentation with an add-on treatment counts as a second treatment. 4) Patients have discontinued any monoaminergic psychiatric medication (i.e. SRIs, antipsychotic medication) for at least 2 weeks (fluoxetine: 5 weeks) before the first dosing session. a. Patients who are still on any monoaminergic psychiatric medication at screening must agree to down-titrate over an individualized down-titration schedule in close supervision by their out-patient psychiatrist and the study team. The treating psychiatrist must agree to supervise and monitor the down-titration and to collaborate with the study team by signing a “treatment agreement form”. b. If the treating psychiatrist refuses to monitor the down-titration, the patient has to agree to down-titrate under supervision of clinicians in the outpatient clinics of the two study sites or trial physicians and to come in for weekly monitoring visits. 5) The subjects are abstinent from alcohol (breathalyzer blood alcohol concentration (BAC) level 0.00) and have a negative urine drug screening at day of dosing. 6) The subject must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead ECG performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, retesting of an abnormal lab value(s) that may lead to exclusion will be allowed once during the screening phase. In 12-lead ECG, QTcF should be = 450 ms for males or = 470 ms for females and PR-interval =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Currently comorbid or previously diagnosed DSM-5 diagnosis of a a. major depressive episode with psychotic features/major depressive disorder with psychotic features (ICD-10: F32.3) b. schizophrenia spectrum and other psychotic disorders, including schizotypal (personality) disorders, delusional disorder, brief psychotic disorder, schizophreniform disorder, schizoaffective disorder, substance/medication-induced psychotic disorder and psychotic disorder due to another medical condition (ICD-10: F20 – F29) c. bipolar and related disorders (ICD-10: F30/F31) d. cluster A personality disorders (paranoid personality disorder, schizoid personality disorder, schizotypal personality disorder) and/or borderline personality disorder i. Patients will be carefully screened for presence of those personality disorders by using the SCID-5-PD. e. Post-traumatic stress disorder (PTSD; ICD-10: F43.1) 2) A family history (first-degree relative) of psychosis and/or bipolar disorder 3) The subject has a current or recent history of clinically significant suicidal ideation within the past 6 months, corresponding to a score of 4 (active suicidal ideation with some intent to act, without specific plan) or 5 (active suicidal ideation with specific plan and intent) for ideation on the C-SSRS, or a history of suicidal behavior within the past 1 year, as validated by the C-SSRS at screening. Subjects with a prior suicide attempt of any sort, or prior serious suicidal ideation/plan > 6 months ago, should be carefully screened for current suicidal ideation and only included at the discretion of the investigator. 4) Current comorbid psychiatric diagnosis except their major diagnosis (inclusion criterion 3) in form of a. Diagnoses mentioned under exclusion criterion 1) b. Substance use disorder (except tobacco-related disorders/caffeinerelated disorders) i. Alcohol consumption must be limited to = 40 gram for men and = 20 gram for women per day, e.g. = two/one large beer (0.5 l) for men/women. 5) Use of classical psychedelics (i.e. LSD, psilocybin, mescaline, dimethyltryptamine) in the past year and or more than five life-time uses of classical psychedelics. 6) Failure to establish sufficient rapport with the two therapists as judged by them after the first two preparation sessions 7) Lithium intake 8) The subject has undergone electroconvulsive therapy (ECT) within twelve months prior to screening or treatment with ketamine or esketamine within six months prior to screening. 9) The subject has received any prior treatment with vagal nerve stimulation, or a deep brain stimulation device.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and efficacy of 25 mg psilocybin (p.o.) in comparison to 5 mg psilocybin (low dose/active placebo) and 100 mg niacin administered in a psychotherapeutic context in treatment-resistant major depression.;Secondary Objective: Secondary objectives are identifying potential (neuro)biological and psychological mediating/moderating variables of the treatment response and/or well-being and additional outcome parameters.;Primary end point(s): Six weeks after the first dose, the number of treatment responders (= 50% reduction in symptoms as measured by HAM-D) will be significantly higher with the 25 mg dose as compared to the sub-therapeutic 5 mg dose of psilocybin, after having made sure in a preliminary step that the higher dose is superior to niacin (= negative control) in terms of the responder rate. Primary endpoint: Hamilton Depression Scale (HAM-D): treatment response defined as = 50% reduction in symptoms six weeks after the first dose.;Timepoint(s) of evaluation of this end point: Timepoint of evaluation of the primary endpoint: 6 weeks after the first dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: (i) the treatment response defined as % reduction in HAM-D and the Beck Depression Inventory (BDI)-II total score from baseline is different between nicotinamide, 5 mg psilocybin and 25 mg psilocybin six weeks after the first dose. (ii) the treatment response (responder rate and % change from baseline; assessed with the HAM-D and BDI-II) will manifest already one day (BDI-II only) and one week, respectively, after administration of 100 mg nicotinamide, 5 mg psilocybin, or 25 mg psilocybin. (iii) the outcome (responder rate and % change from baseline; assessed with the HAMD and BDI-II) after 12 weeks differs between the following 4 treatment arms: 1) 100 mg nicotinamide as first dose plus 25 mg psilocybin as second dose; 2) 5 mg psilocybin as first dose plus 25 mg psilocybin as second dose; 3a) 25 mg psilocybin as first dose plus 5 mg psilocybin as second dose; 3b) 25 mg psilocybin as both first and second dose. (iv) rates of remitters (HAM-D total score < 8 points and BDI-II < 10) after one, six and 12 weeks will differ between the 4 treatment arms. (v) outcomes will remain significant at the follow-up assessments, six and twelve months after the first dose (follow-up). Safety Parameters: • Vital signs • ECG • Blood laboratory • Suicidality: Columbia-Suicide Severity rating Scale (C-SSRS) • Side effects: UKU side effects rating scale • Dissociation: DSS-4 • AEs/SAEs;Timepoint(s) of evaluation of this end point: Timepoints of evaluation of those endpoints: - one day (BDI-II and safety assessments only), one week, six weeks, and 12 weeks after the first dose - follow-ups: 6 and 12 months after the first dose | — |
Countries
Germany
Contacts
Public ContactSponsor representative
Central Institute of Mental Health
Outcome results
None listed