Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin
- PMID: 38359838
- DOI: 10.1016/j.medj.2024.01.005
Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin
Abstract
Background: Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period.
Methods: Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466).
Findings: Participants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p < 0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline.
Conclusions: PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity.
Funding: This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific.
Keywords: Translation to patients; bipolar affective disorder; bipolar disorder; borderline personality disorder; depressive disorders; major depressive disorder; persistent depressive disorder; psilocybin; psychedelics; psychotherapy; real world effectiveness.
Copyright © 2024 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests J.D.R. has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services, Inc. (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Center for Mental Health, Joseph M. West Family Memorial Fund, and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Janssen, Allergan, Lundbeck, Sunovion, Braxia Health, Braxia Scientific Corp., and COMPASS. R.S.M. has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC), and the Milken Institute and speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. R.S.M. is a CEO of Braxia Scientific Corp. C.S.-Q. has received education scholarship support from Academic Scholars Award, Department of Psychiatry, University of Toronto, and Young Leaders Program and Cancer Experience Program, Princess Margaret Cancer Center, University Health Network. He is on the board of directors for the Canadian Academy for Consultation and Liaison Psychiatry. M.G.B. currently works as an independent contractor serving clients for psychedelic-assisted psychotherapy with Braxia Scientific Corp.; in a consulting role, he owns stake in a psychedelic technology company called Entheosense and has received speaking fees as an honorarium for providing a training lecture on psychedelic spiritual care for psychotherapists in this Braxia clinical trial. R.B.M. has received research grant support from the CIHR, the PSI Foundation, and the Baszucki Brain Research Fund and an Academic Scholars Award, Department of Psychiatry, University of Toronto. F.A.G. has received research grant support from the Brain & Behavior Research Foundation (BBRF), Southeastern Ontario Academic Medical Organization (SEAMO), and Queen’s Health Sciences and speaker/consultation fees from Lundbeck, Otsuka, and Abbvie. Z.D., RN, is a clinical project lead with Braxia Scientific Corp. J.B. was a paid co-chair of a psilocybin therapist training event with Braxia Scientific Corp.
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