Division of Adult Psychiatry, Department of Psychiatry, University Hospitals of Geneva, 2, Chemin du Petit-Bel-Air, CH-1226, Thonex, Switzerland.
Univ Paris-Est Créteil, DMU IMPACT, Département Médical-Universitaire de Psychiatrie et d'Addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France; Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, Geneva, Switzerland.
Eur Neuropsychopharmacol. 2023 Nov;76:61-76. doi: 10.1016/j.euroneuro.2023.07.011. Epub 2023 Aug 7.
Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.
裸盖菇素因其抗抑郁作用而越来越受到研究关注，但用于治疗抑郁症的最佳剂量仍不清楚。我们进行了系统评价和剂量-反应荟萃分析，以确定降低抑郁评分的最佳裸盖菇素剂量。根据我们的方案（CRD42022220190），从成立之初到 2023 年 2 月，我们在多个电子数据库中搜索了双盲随机安慰剂对照（RCT）固定剂量试验，以评估裸盖菇素用于治疗成人原发性或继发性抑郁症的效果。采用一阶剂量反应荟萃分析和限制立方样条。使用 Cochrane 偏倚风险评估来评估偏倚风险。我们的分析包括 7 项研究，共 489 名参与者。其中，4 项研究专注于原发性抑郁症（N=366），包括一项针对治疗抵抗性抑郁症患者的研究。其余 3 项研究检查了继发性抑郁症（N=123）。确定的每日 95%有效剂量（ED95）分别为 8.92、24.68 和 36.08mg/70kg，用于继发性、原发性和两个亚组的患者。我们观察到所有曲线均存在显著的剂量反应关系，除了在继发性抑郁症的情况下观察到钟形曲线外，每个曲线都在不同水平上达到平台。此外，我们还发现了各种副作用的显著剂量反应关系，包括身体不适、血压升高、恶心/呕吐、头痛/偏头痛以及延长精神病风险。总之，我们为不同人群发现了特定的 ED95 值，表明治疗抵抗性抑郁症、原发性抑郁症和继发性抑郁症人群的 ED95 值较高。需要为每个人群进行更多的 RCT，以确定最佳剂量，在最大程度提高疗效的同时最大限度减少副作用。
