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

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Med Pub Date : 2024-03-08 Epub Date: 2024-02-14 DOI:10.1016/j.medj.2024.01.005

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

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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.

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治疗抗药性抑郁症的迷幻剂辅助心理疗法：一项评估重复剂量迷幻药的随机临床试验。

背景：迷幻药辅助心理疗法（PAP）具有抗抑郁效果。迄今为止的试验通常排除了具有复杂表现的参与者。我们的目的是确定 PAP 在复杂人群中的可行性，包括重度抑郁症和双相情感障碍中的高抗治疗性患者，以及有基线自杀倾向和严重合并症的患者。我们还对 6 个月内的灵活重复剂量进行了评估：方法：患有重度抑郁症或双相情感障碍 II 且无精神病或药物使用障碍的成人患者均有资格参与。受试者被随机分配到立即治疗或候补对照组，最终都接受了 PAP 治疗。受试者接受了一次、两次或三次固定剂量为 25 毫克的迷幻剂治疗。每次用药前都会进行准备和整合心理治疗。对接受度、安全性、耐受性和疗效进行了评估（该研究已在 ClinicalTrials.gov 注册：NCT05029466）：参与者被随机分配到立即治疗（16 人）或延迟治疗（14 人）。29/30的参与者保留到了第2周的主要终点。不良反应均为一过性，无严重不良反应。通过蒙哥马利-阿斯伯格抑郁评定量表（MADRS）测量，立即治疗组与等待治疗组相比，抑郁严重程度降低幅度更大，对冲 g效应大小为 1.07（p 结论：PAP 在复杂患者中是可行的：PAP对复杂患者是可行的，具有初步的抗抑郁疗效和足够的安全性和耐受性。重复剂量与抑郁症严重程度的进一步减轻有关：本研究得到了脑与认知发现基金会（BCDF）、Usona和Braxia Scientific的资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.