Psilocybin treatment for patients with severe depression

Psilocybin-assisted Psychotherapy in the Treatment of Patients Hospitalized for Treatment-resistant Depression: an Open-label Feasibility Study with an Experiential and Systemic Focus

This study is testing if psilocybin therapy can help hospitalized patients with severe depression who haven't found relief from other treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Ghent (other)
• Locations: 1 site (Ghent, Oost-Vlaanderen)
• Trial ID: NCT06378229 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and feasibility of psilocybin-assisted psychotherapy for hospitalized patients suffering from treatment-resistant depression. Participants will undergo a structured program that includes preparatory therapy sessions, two psilocybin sessions, and follow-up integration therapy. The study aims to assess both the psychological and neurological effects of this treatment approach over an 8-week hospitalization period, followed by outpatient consultations. The goal is to provide a comprehensive understanding of how psilocybin can aid in treating severe depression in a clinical setting.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of major depressive disorder who have not responded to multiple antidepressant treatments.

Not a fit: Patients with psychotic features or those who are not medically stable may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with severe depression who have not responded to traditional antidepressants.

How similar studies have performed: Other studies have shown promising results with psilocybin in treating depression, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years or older.
2. Diagnosis of major depressive disorder (single and recurrent episodes) of moderate to severe degree (MADRS score ≥ 20) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), without psychotic features. Included ICD-11 diagnoses are ICD-11: 6A70.1, 6A70.3, 6A71.1, 6A71.3.
3. Subjects have failed to respond to 2 or more antidepressants prescribed at the minimum effective dose for at least 6 weeks. Augmentation with an add-on treatment counts as a second treatment.
4. The subjects are abstinent from alcohol (breathalyzer blood alcohol concentration (BAC) level 0.00) and provide a negative urine drug screen at the dosing day.
5. The female subjects provide a negative pregnancy test at the dosing day.
6. The subjects must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead ECG performed at screening.

   \- In 12-lead ECG, QTcF should be ≤ 450 ms for males or ≤ 470 ms for females and PR-interval \< 220 ms at screening.
7. A partner is willing to participate in the study (a cohabiting relationship of at least 1 year).

Exclusion Criteria:

1. Currently comorbid or previously diagnosed DSM-5 diagnosis of a

   1. major depressive episode with psychotic features.
   2. psychotic disorder (defined as meeting DSM-5 criteria for any psychotic disorder) on the MINI 7.0, EXCEPT substance/medication induced psychotic disorder where the duration was limited to the acute period of direct intoxication with the substance/medication. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
   3. bipolar disorder (defined as meeting DSM-5 criteria for bipolar type 1 or bipolar type 2) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
   4. drug or alcohol dependence syndrome (defined as meeting DSM-5 criteria for any dependence syndrome) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
   5. cluster B personality disorder. Subjects will be screened for the presence of those personality traits by using the NEO-FFI-3.
   6. PTSD (defined as meeting DSM-5 criteria for PTSD) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
2. A family history (first-degree relative) of psychosis and/or bipolar disorder.
3. Current active suicidal ideations.
4. Depression secondary to other medical conditions.
5. Medical diagnosis incompatible with psilocybin treatment:

   1. Cardiovascular conditions: recent stroke (\< 1 year from signing of ICF), recent myocardial infarction (\< 1 year from signing of ICF), uncontrolled hypertension (blood pressure \> 140/90 mmHg) or clinically significant arrhythmia within 1 year of signing the ICF.
   2. Uncontrolled insulin-dependent diabetes mellitus.
   3. Uncontrolled epilepsy.
6. Biochemical or electrocardiographic abnormalities determined as clinically significant by a medical doctor. PsiHos-D, Version 2.1 dd. 22/02/2024 page 59 of 114 TMP\_Protocol AGO CTR\_Version 1.0\_Effective Date 2022-07-18
7. Current intake of Lithium, Disulfiram, MAOIs or inhibitors of UGT1A9 and 1A10.
8. The subject has received any prior treatment with vagal nerve stimulation, or a deep brain stimulation device.
9. Women of childbearing potential not using adequate contraception (methods that can achieve a failure rate of less than 1%: combined hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence). A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
10. Pregnant or breast-feeding women.
11. Those unable to give informed consent.
12. Those enrolled in another trial.

Where this trial is running

Ghent, Oost-Vlaanderen

• Ghent University Hospital — Ghent, Oost-Vlaanderen, Belgium (RECRUITING)

Study contacts

• Principal investigator: Gilbert Lemmens, Prof. dr. — University Hospital, Ghent
• Study coordinator: Cisse Geleyn, dr.

Conditions: Treatment Resistant Depression