Reckweg Johannes T, van Leeuwen Cees J, Henquet Cécile, van Amelsvoort Therese, Theunissen Eef L, Mason Natasha L, Paci Riccardo, Terwey Theis H, Ramaekers Johannes G
Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands.
Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
Front Psychiatry. 2023 Jun 20;14:1133414. doi: 10.3389/fpsyt.2023.1133414. eCollection 2023.
Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD.
The Phase 1 part ( = 8) of the trial investigated two single dose levels of GH001 (12 mg, 18 mg) with a primary endpoint of safety, and the Phase 2 part ( = 8) investigated an individualized dosing regimen (IDR) with up to three increasing doses of GH001 (6 mg, 12 mg, and 18 mg) within a single day, with a primary endpoint of efficacy, as assessed by the proportion of patients in remission (MADRS ≤ 10) on day 7.
Administration of GH001 via inhalation was well tolerated. The proportion of patients in remission (MADRS ≤ 10) at day 7 was 2/4 (50%) and 1/4 (25%) in the 12 mg and 18 mg groups of Phase 1, respectively, and 7/8 (87.5%) in the IDR group of Phase 2, meeting its primary endpoint ( < 0.0001). All remissions were observed from day 1, with 6/10 remissions observed from 2 h. The mean MADRS change from baseline to day 7 was -21.0 (-65%) and - 12.5 (-40%) for the 12 and 18 mg groups, respectively, and - 24.4 (-76%) for the IDR.
Administration of GH001 to a cohort of 16 patients with TRD was well tolerated and provided potent and ultra-rapid antidepressant effects. Individualized dosing with up to three doses of GH001 on a single day was superior to single dose administration.: Clinicaltrials.gov Identifier NCT04698603.
难治性抑郁症（TRD）是一项重大的公共卫生负担，但目前的治疗效果有限。本研究旨在调查5-甲氧基-N,N-二甲基色胺（5-MeO-DMT）这种血清素能致幻药物的汽化制剂（GH001）在成年TRD患者中的安全性和潜在抗抑郁作用。
试验的1期部分（n = 8）研究了GH001的两个单剂量水平（12毫克、18毫克），主要终点为安全性；2期部分（n = 8）研究了个体化给药方案（IDR），在一天内给予高达三个递增剂量的GH001（6毫克、12毫克和18毫克），主要终点为疗效，通过第7天缓解患者（蒙哥马利-艾森伯格抑郁量表评分≤10）的比例进行评估。
通过吸入方式给予GH001耐受性良好。1期的12毫克和18毫克组在第7天的缓解患者比例分别为2/4（50%）和1/4（25%），2期的IDR组为7/8（87.5%），达到了主要终点（P < 0.0001）。所有缓解均在第1天观察到，其中6/10的缓解在2小时内观察到。12毫克和18毫克组从基线到第7天的蒙哥马利-艾森伯格抑郁量表平均变化分别为-21.0（-65%）和-12.5（-40%），IDR组为-24.4（-76%）。
对16名TRD患者给予GH001耐受性良好，并产生了强效和超快速的抗抑郁作用。一天内给予高达三剂GH001的个体化给药方案优于单剂量给药。：临床试验.gov标识符NCT04698603。
