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 (New York, N.Y.) March 8, 2024 DOI: 10.1016/j.medj.2024.01.005 via PubMed
Summary
AI-generated from the abstractPsilocybin-assisted psychotherapy (PAP) is feasible for patients with complex, treatment-resistant depression, including those with bipolar II disorder and baseline suicidality. In a randomized trial with 30 adults, those receiving immediate PAP showed greater reductions in depression severity (MADRS) compared to a waitlist control, with a large effect size (Hedge's g = 1.07). Adverse events were transient and no serious adverse events occurred. Repeated doses over six months were associated with further improvement. The findings suggest PAP can be safely delivered to this population and warrants further study.
Study at a glance
| 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 |
| Citations | 97 |
| Registration | NCT05029466 |
| Key finding | 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.