Exploratory safety, tolerability, and feasibility of psilocybin-assisted psychotherapy for adults with co-occurring treatment-resistant depression and cluster B personality disorders

Cluster B personality disorders (PDs) are highly comorbid with depression and are associated with attenuated antidepressant response. No clinical trials to date have reported on psilocybin-assisted psychotherapy (PAP) in comorbid treatment-resistant depression (TRD) and PDs. This is the first clinical trial to describe a subgroup of ten participants with a comorbid PD (n = 9 cluster B; n = 1 cluster C) and TRD who underwent PAP, representing a secondary analysis of a larger trial.

The trial was registered on clinicaltrials.gov under the identifier NCT05029466 (Registration Date: 2021-08-26). Three participants dropped out of the trial. Mean MADRS scores decreased from 30.4 pre-treatment to 22.5 at day 1, 24.9 at week 2, and 22.3 at month 6.

Mean MADRS Suicidal ideation (SI) item declined from 3.2 to 1.6 at day 1, 2.3 at week 2, and 1.2 at month 6. There was substantial heterogeneity in outcomes amongst participants. No serious adverse events were recorded.

This is the first clinical trial evidence that PAP may reduce depression and SI in comorbid cluster B PDs, suggesting further trials may be warranted. The Brain and Cognition Discovery Foundation (BCDF) was the study sponsor, with additional in-kind support provided by Usona (supplying synthetic psilocybin at no cost) and Braxia Scientific Corp. (allowing for use of clinic facilities and administrative support at no cost). Additional funding was provided post-trial from Dr.

While Braxia Scientific Corp. had no formal role in study design, it is noteworthy that J.D.R. was the chief medical and scientific officer (during part of the trial but not at the time of study design or data analysis) and that R.S.M. was the chief executive officer of Braxia Scientific Corp. Usona had no role in the design, data collection, analysis, interpretation, or writing of the report. R.S.M. (chairman of BCDF and study sponsor) had a dual role as co-investigator and did contribute to study design and writing of the present report; however, R.S.M. did not participate in any data collection or analysis, with no direct access to the data at any time.

The corresponding author had full access to all of the data in the study and had final responsibility for the decision to submit for publication. Department of Psychological Clinical Science, University of Toronto, Toronto, ON, Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada Erica S. Rosenblat Department of Psychiatry, University of Toronto, Toronto, ON, Canada Shakila Meshkat, Rickinder Sethi, Roger S.