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

Prior treatment

• 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

Other illness

• 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

Lab values

• Cardiovascular history (myocardial infarction, stroke, heart rhythm disorder, uncontrolled hypertension, QT interval prolongation, tachycardia and poor cardiovascular health)

Other

• 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

• 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