Efficacy of psilocybin and trazodone combination in treatment-resistant depression: a randomized controlled proof-of-concept study (PSILOTRAZ)

Trial details

Who runs it

Groupe Hospitalier Universitaire Paris Psychiatrie & Neuroscience

Trial code

EU 2024-512911-34-00

Record updated

2026. május 18.

Original description

To evaluate the efficacy of a single administration of the combination of psilocybin 25 mg + trazodone 30 mg (compared to placebo), administered with psychotherapeutic support in adult patients with TRD, in improving symptoms of depression at 1 month.Read full original descriptionShow less

To evaluate the efficacy of a single administration of the combination of psilocybin 25 mg + trazodone 30 mg (compared to placebo), administered with psychotherapeutic support in adult patients with TRD, in improving symptoms of depression at 1 month.

Inclusion: Age ≥ 18 years old; Patient with major depressive episode without psychotic features according to DSM-5 criteria; MADRS score ≥ 20; Treatment-resistant depressive episode, i.e. failure to respond to at least two lines of antidepressant medication at an adequate dose and for a sufficient period of time (6 weeks according to the MGH-ATRQ); Free, informed and prior written consent of the patient; Persons covered by the social security system.

Exclusion: Contraindications to MRI: Implants (mechanical or electronic: cochlear implants, pacemakers, infusion pumps, magnetic clips, etc.) incompatible with the magnetic field; Metallic foreign bodies in the eye or nervous system; Claustrophobia; Non-removable dental removable braces; Treatment with buprenorphine or opioids; Patient with a psychiatric decompensation following a previous use of psychedelic substance like LSD; Concomitant therapies; Bipolar disorder; Uncontrolled thyroid disorder; Epilepsy; Persons deprived of their liberty by judicial or administrative decision, persons under compulsory psychiatric care; Parkinson’s disease treated by selegiline or levodopa; HIV treated by ritonavir and indinavir; Active infection treated by erythromycin; Fungal infection treated by ketoconazole and itraconazole; Personal or family history of psychotic disorder; History of personality disorder; Post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders; Alcohol or substance use disorder in past 12 months or positive urine toxins at time of assessment; Uncontrolled diabetes; Cardiovascular history (myocardial infarction, stroke, heart rhythm disorder, uncontrolled hypertension, QT interval prolongation, tachycardia and poor cardiovascular health); Significant suicide risk, as defined by: (a) suicidal ideation as indicated by items 4 or 5 on the C-SSRS within the past six months, at Screening, during the Screening Period, or at Baseline (b) demonstrating suicidal behaviors in the past six months, or; (c) clinical assessment of significant suicidal risk or risk of self-injury during participant interview; 5-HT2A antagonist treatment (including quetiapine, olanzapine, aripiprazole); Lithium treatment; Use of psychedelics (psilocybin, lysergic acid, ayahuasca, mescaline and derivatives) during current episode; Persons under legal protection or unable to give consent; Any clinical event that, in the opinion of the investigator, may interfere with the interpretation of study results or constitute a health risk to the participant if he or she participates in the study; Schizophrenia and psychosis; Legal status; Other: Any clinical manifestation which, in the opinion of the investigator, may interfere with the interpretation of study results or constitute a health risk to the participant if he or she participates in the study; Pregnancy and breastfeeding women.

EU CTIS 2024-512911-34-00