Swieczkowski Damian, Kwaśny Aleksander, Pruc Michal, Gaca Zuzanna, Szarpak Lukasz, Cubała Wiesław J
Department of Clinical Research and Development, LUXMED Group, Warsaw, Poland; Department of Toxicology, Faculty of Pharmacy, Medical University of Gdansk, Poland.
Department of Psychiatry, Faculty of Medicine, Medical University of Gdansk, Gdansk, Poland.
Psychiatry Res. 2025 Feb;344:116337. doi: 10.1016/j.psychres.2024.116337. Epub 2024 Dec 23.
Selecting the optimal dose of psilocybin for treating Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD) is crucial for clinical development and regulatory approval. This meta-analysis evaluates psilocybin's efficacy and safety in treating MDD to determine the optimal dose and timing for clinical trials. A systematic review and Dose-Response Network Meta-Analysis (NMA) of Randomized Placebo-Controlled Clinical Trials (RCTs) registered with PROSPERO was conducted. Databases searched included Embase, PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar, up to July 2024. The PICOS framework defined eligibility criteria: P: adult patients with MDD; I: psilocybin; C: placebo; O: changes in MADRS scores at Days 2, 8 and 15, and adverse events; S: RCT. Independent researchers performed data extraction and bias assessment. From 5419 search results, three RCTs involving 389 patients were included. Psilocybin significantly reduced symptoms compared to placebo at Day 8 (MD = -7.42; 95 % CI:10.07 to -4.78; p < 0.001) and Day 15 (MD = -9.55; 95 % CI:12.44 to -6.65; p < 0.001), without significant effects on Day 2. The NMA indicated that a 25 mg dose was the most effective, with a SUCRA value of 92.25 %, compared to doses of 0.215 mg/kg and 10 mg. However, psilocybin was associated with a higher risk of adverse events, particularly nausea (RR = 8.35; p < 0.001). This meta-analysis supports psilocybin's efficacy in treating MDD, particularly at a 25 mg dose, showing a time-dependent therapeutic effect. The recommended timing of efficacy evaluation by regulatory authorities is validated by this evidence, underscoring its importance in clinical trial design for psychedelic substances.
选择裸盖菇素治疗重度抑郁症（MDD）和难治性抑郁症（TRD）的最佳剂量对于临床开发和监管批准至关重要。这项荟萃分析评估了裸盖菇素治疗MDD的疗效和安全性，以确定临床试验的最佳剂量和时间。对在PROSPERO注册的随机安慰剂对照临床试验（RCT）进行了系统评价和剂量反应网络荟萃分析（NMA）。检索的数据库包括截至2024年7月的Embase、PubMed、Cochrane图书馆、Scopus、科学网和谷歌学术。PICOS框架定义了纳入标准：P：患有MDD的成年患者；I：裸盖菇素；C：安慰剂；O：第2、8和15天蒙哥马利-艾森伯格抑郁量表（MADRS）评分的变化以及不良事件；S：RCT。独立研究人员进行了数据提取和偏倚评估。从5419个搜索结果中，纳入了3项涉及389名患者的RCT。与安慰剂相比，裸盖菇素在第8天（MD = -7.42；95%CI：-10.07至-4.78；p < 0.001）和第15天（MD = -9.55；95%CI：-12.44至-6.65；p < 0.001）显著减轻症状，在第2天无显著效果。NMA表明，与0.215mg/kg和10mg剂量相比，25mg剂量最有效，累积排序曲线下面积（SUCRA）值为92.25%。然而，裸盖菇素与更高的不良事件风险相关，尤其是恶心（RR = 8.35；p < 0.001）。这项荟萃分析支持裸盖菇素治疗MDD的疗效，尤其是25mg剂量，显示出时间依赖性治疗效果。监管机构推荐的疗效评估时间通过该证据得到验证，强调了其在迷幻物质临床试验设计中的重要性。
