Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Med Pub Date : 2025-06-04 DOI:10.1016/j.medj.2025.100725
Felix Müller, Hannes Zaczek, Anna M Becker, Laura Ley, Stefan Borgwardt, Joyce Santos de Jesus, Nico Loh, Jan Kohut, Mathias Auernig, Christopher Boehlke, Matthias E Liechti
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引用次数: 0

Abstract

Background: This trial aimed to assess the efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with moderate-to-severe major depressive disorder.

Methods: This was a randomized, parallel, double-blind, low-dose controlled trial (Clinicaltrials.gov: NCT03866252). Patients were randomly assigned in a 1:1 ratio to receive supportive psychotherapy and either 100 μg + 200 μg LSD or 25 μg + 25 μg LSD in two dosing sessions. The primary endpoints were the changes in scores on the Inventory of Depressive Symptomatology, in the Clinician-Rated (IDS-C) version (assessed by the treating therapist) and the Self-Rated (IDS-SR) version, from baseline to 2 weeks after the second administration. The IDS scores were also assessed 6 and 12 weeks after the second administration.

Findings: Thirty-one patients were randomized to the low-dose group, and 30 were randomized to the high-dose group. At the primary endpoint, least-squares mean change (LSM) in IDS-SR scores was -3.9 in the low-dose and -11.8 in the high-dose group (difference: -7.9; 95% CI, -16.0 to 0.3; effect size: -0.5; p = 0.059). LSM in IDS-C scores was -3.6 in the low-dose and -12.9 in the high-dose group (difference: -9.2; CI, -17.1 to -1.3; effect size: -0.6; p = 0.023; corrected <0.05). However, significance was not reached after adjusting for baseline depression scores (p = 0.086). Both outcomes remained numerically consistent up to the final follow-up at 12 weeks. Adverse events were comparable between groups.

Conclusions: The findings of this exploratory study support further investigation of LSD-assisted therapy in depression in a larger phase 3 trial.

Funding: Gertrud Thalmann Fund for depression research.

低剂量与高剂量lsd辅助治疗重度抑郁症患者的疗效和安全性:一项随机试验。
背景:本试验旨在评估麦角酸二乙胺(LSD)辅助治疗中重度抑郁症患者的疗效。方法:这是一项随机、平行、双盲、低剂量对照试验(Clinicaltrials.gov: NCT03866252)。患者按1:1的比例随机分配,接受支持性心理治疗和100 μg + 200 μg LSD或25 μg + 25 μg LSD,分两次给药。主要终点是在第二次给药后从基线到2周,临床评定(IDS-C)版本(由治疗治疗师评估)和自评定(IDS-SR)版本的抑郁症状量表得分的变化。在第二次给药后6周和12周也评估IDS评分。结果:31例患者随机分为低剂量组,30例随机分为高剂量组。在主要终点,低剂量组IDS-SR评分的最小二乘平均变化(LSM)为-3.9,高剂量组为-11.8(差异:-7.9;95% CI, -16.0 ~ 0.3;效应量:-0.5;P = 0.059)。低剂量组IDS-C评分LSM为-3.6,高剂量组为-12.9(差异:-9.2;CI, -17.1 ~ -1.3;效应量:-0.6;P = 0.023;这项探索性研究的结果支持在更大的三期试验中进一步研究lsd辅助治疗抑郁症。资助:格特鲁德·塔尔曼抑郁症研究基金。
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
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.
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