Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized … (NCT07210112) | Clinical Trial Compass
Not Yet RecruitingPhase 2
Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ)
France112 participantsStarted 2025-10-08
Plain-language summary
Psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improves depressive symptoms while inducing profound acute subjective effects.
The benefit-risk ratio of psilocybin in treatment-resistant depression seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on the therapeutic efficacy of psilocybin is still poorly understood. For example, pre-administration of trazodone, a 5-HT2A antagonist antidepressant, could annihilate the acute subjective effects of psilocybin without altering its beneficial effects (Rosenblat et al., 2023). We intend to test this hypothesis by comparing, in a randomized, double-blind, placebo-controlled study, the effect of two possible doses of trazodone (total or partial occupancy of 5-HT2A receptors) on the benefit/risk ratio of psilocybin.
We hypothesize that the therapeutic effects of psilocybin are partially independent of 5-HT2A receptor activation and thus persist even after total or partial neutralization of its acute subjective effects.
Who can participate
Age range18 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Patient with major depressive episode without psychotic features according to DSM-5 criteria;
* 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);
* MADRS ≥ 20;
* Written signed informed consent;
* Patient covered by the social security system.
Exclusion Criteria:
Psychiatric comorbidities known from medical history or identified during inclusion assessment:
* Bipolar disorder;
* Schizophrenia and psychosis;
* 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;
* 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;
* Patient with a psychiatric decompensation following a previous use of psychedelic substance like LSD;
Comorbidities or somatic specificities:
* Pregnancy and breastfeeding women;
* Cardiovascular history (myocardial infarction, stroke, heart rhythm disorder, unco…
What they're measuring
1
Change from Baseline in the mean score of Montgomery-Ã…sberg Depression Rating Scale (MADRS) at 1 month