Goodwin Guy M, Nowakowska Ania, Atli Merve, Dunlop Boadie W, Feifel David, Hellerstein David J, Marwood Lindsey, Shabir Zainib, Mistry Sunil, Stansfield Susan C, Teoh Emma, Tsai Joyce, Young Matthew B, Malievskaia Ekaterina
Compass Pathfinder Ltd (a subsidiary of Compass Pathways plc), London, United Kingdom.
Corresponding Author: Guy M. Goodwin, MD, Compass Pathfinder Ltd, FORA Soho, 33 Broadwick St, London W1F 0DQ, United Kingdom (
J Clin Psychiatry. 2025 Mar 3;86(1):24m15449. doi: 10.4088/JCP.24m15449.
The largest randomized study of psilocybin to date demonstrated the efficacy of COMP360 25 mg (Compass Pathways' investigational proprietary pharmaceutical-grade synthesized psilocybin formulation) in participants with treatment-resistant depression (COMP 001), compared with 10 mg and 1 mg doses. Here, we report findings from COMP 004, a 52-week observational follow-up of patients from COMP 001 and COMP 003, a small open-label study of the coadministration of 25 mg COMP360 with continuing antidepressant treatment. Adverse events (AEs) were collected over the full 52-week period. The primary efficacy endpoint was time to a prespecified depressive event over the 52 weeks following COMP360 administration in COMP 001 participants, presented as Kaplan-Meier estimates. A post hoc analysis included only participants that entered COMP 004. Data were collected from July 2020 to July 2022. Sixty-six participants entered COMP 004 (COMP 001, n = 58 [25 mg group n = 22, 10 mg group n = 19, 1 mg group n = 17]; COMP 003, n = 8). Few AEs were reported post-entry into COMP 004, with 1 AE of mild suicidal ideation in the 1 mg group deemed possibly related to study drug. For all COMP 001 patients (n = 233), median time to depressive event was greater for the 25 mg group (92 days) compared to the 10 mg (83 days) and 1 mg (62 days) groups, with the majority of participants having had a depressive event by Week 12 (25 mg n = 37/75, 10 mg n = 38/79, 1 mg n = 44/75). The post hoc supplementary analysis of those who enrolled in COMP 004 from COMP 001 exhibited the difference between groups more strikingly (25 mg, 189 days; 10 mg, 43 days; 1 mg, 21 days); however, only 10 participants experienced a depressive event post-COMP 004 enrollment (25 mg n = 6, 10 mg n = 3, 1 mg n = 1) from COMP 001 and none from COMP 003. At COMP 004 entry, the 1 mg group had the highest number of participants on antidepressant medication (n = 10; 10 mg, n = 9; 25 mg, n = 6) and generally initiated treatment earlier. Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg. Larger long-term studies are required to confirm these findings and provide clarity on the longer-term effects of psilocybin. ClinicalTrials.gov identifier: NCT04519957.
迄今为止，关于裸盖菇素的最大规模随机研究表明，与10毫克和1毫克剂量相比，COMP360 25毫克（Compass Pathways公司研究用的专利医药级合成裸盖菇素制剂）对难治性抑郁症患者有效（COMP 001）。在此，我们报告COMP 004的研究结果，这是一项对COMP 001和COMP 003患者进行的为期52周的观察性随访研究，COMP 003是一项关于25毫克COMP360与持续抗抑郁治疗联合使用的小型开放标签研究。在整个52周期间收集不良事件（AE）。主要疗效终点是COMP 001参与者在服用COMP360后的52周内发生预先指定的抑郁事件的时间，以Kaplan-Meier估计值表示。一项事后分析仅纳入进入COMP 004的参与者。数据收集时间为2020年7月至2022年7月。66名参与者进入COMP 004（COMP 001，n = 58 [25毫克组n = 22，10毫克组n = 19，1毫克组n = 17]；COMP 003，n = 8）。进入COMP 004后报告的不良事件很少，1毫克组有1例轻度自杀意念不良事件被认为可能与研究药物有关。对于所有COMP 001患者（n = 233），25毫克组的抑郁事件中位时间（92天）长于10毫克组（83天）和1毫克组（62天），大多数参与者在第
