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Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin.

Joshua D. Rosenblat, Shakila Meshkat, Zoe Doyle, Erica Kaczmarek, Ryan M Brudner, Kevin Kratiuk, Rodrigo B. Mansur, Christian Schulz-Quach, Rickinder Sethi, Amanda Abate, Shaun Ali, Jordan Bawks, Marc G Blainey, Elisa Brietzke, Victoria Cronin, Jessica Danilewitz, Shalini Dhawan, Anthony Di Fonzo, Melissa Di Fonzo, Pawel Drzadzewski, William Dunlop, Hajnalka Fiszter, Fabiano A. Gomes, Smrita Grewal, Marisa Leon-Carlyle, Marilyn McCallum, Niki Mofidi, Hilary Offman, Jeremy Riva-Cambrin, Joel Schmidt, Mark Smolkin, Joan M Quinn, Andrea Zumrova, Michelle Marlborough, Roger S McIntyre

Med March 8, 2024 DOI: 10.1016/j.medj.2024.01.005 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 30
Population Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or substance use disorder
Intervention Psilocybin-assisted psychotherapy
Dose 25 mg
Duration 6-month period with repeated doses; primary endpoint at 2 weeks
Topics Depression Psilocybin Psychedelic-assisted therapy
Keywords Translation to patients Bipolar affective disorder Bipolar disorder Borderline personality disorder Depressive disorders Persistent depressive disorder Psychedelics Psychotherapy Real world effectiveness Psilocybin research Mental health breakthroughs Clinical psychiatry
Citations 97
Registration NCT05029466
Key findings Psilocybin-assisted psychotherapy was feasible and associated with greater reductions in depression severity compared to waitlist control in a complex patient population.

Abstract

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. 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). 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. 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. This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific.

Comparable studies

Other randomized controlled trials on psilocybin and psychedelic-assisted therapy, most cited first.

Study Year Design Participants
Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Healthy adults, mostly hallucinogen-naïve 2011 Randomized controlled trial n = 18
Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder Adults aged 25–65 with DSM-IV alcohol dependence and at least 4 heavy drinking days in... 2022 Randomized controlled trial n = 95
Increased global integration in the brain after psilocybin therapy for depression. Patients with treatment-resistant depression and patients with major depressive disorder 2022 Open-label trial and double-blind phase II randomized controlled trial
Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. Adults diagnosed with major depressive disorder and no unstable somatic conditions 2023 Double-blind, randomised clinical trial n = 52
Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin Healthy participants 2012 Randomized controlled trial n = 10

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