Objective To evaluate the comparative effectiveness and acceptability of oral monotherapy using psychedelics and escitalopram in patients with depressive symptoms, considering the potential for overestimated effectiveness due to unsuccessful blinding. Design Systematic review and Bayesian network meta-analysis. Data sources Medline, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, ClinicalTrial.gov, and World Health Organization’s International Clinical Trials Registry Platform from database inception to 12 October 2023. Eligibility criteria for selecting studies Randomised controlled trials on psychedelics or escitalopram in adults with depressive symptoms. Eligible randomised controlled trials of psychedelics (3,4-methylenedioxymethamphetamine (known as MDMA), lysergic acid diethylamide (known as LSD), psilocybin, or ayahuasca) required oral monotherapy with no concomitant use of antidepressants. Data extraction and synthesis The primary outcome was change in depression, measured by the 17-item Hamilton depression rating scale. The secondary outcomes were all cause discontinuation and severe adverse events. Severe adverse events were those resulting in any of a list of negative health outcomes including, death, admission to hospital, significant or persistent incapacity, congenital birth defect or abnormality, and suicide attempt. Data were pooled using a random effects model within a Bayesian framework. To avoid estimation bias, placebo responses were distinguished between psychedelic and antidepressant trials. Results Placebo response in psychedelic trials was lower than that in antidepression trials of escitalopram (mean difference −3.90 (95% credible interval −7.10 to −0.96)). Although most psychedelics were better than placebo in psychedelic trials, only high dose psilocybin was better than placebo in antidepression trials of escitalopram (mean difference 6.45 (3.19 to 9.41)). However, the effect size (standardised mean difference) of high dose psilocybin decreased from large (0.88) to small (0.31) when the reference arm changed from placebo response in the psychedelic trials to antidepressant trials. The relative effect of high dose psilocybin was larger than escitalopram at 10 mg (4.66 (95% credible interval 1.36 to 7.74)) and 20 mg (4.69 (1.64 to 7.54)). None of the interventions was associated with higher all cause discontinuation or severe adverse events than the placebo. Conclusions Of the available psychedelic treatments for depressive symptoms, patients treated with high dose psilocybin showed better responses than those treated with placebo in the antidepressant trials, but the effect size was small. Systematic review registration PROSPERO, CRD42023469014. The data that support the findings of this study are available from the corresponding author (C-SL) upon reasonable request.

中文翻译：

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裸盖菇素、麦角酸二乙胺、3,4-亚甲二氧基甲基苯丙胺、死藤水和艾司西酞普兰的口服单药治疗抑郁症状的比较：系统评价和贝叶斯网络荟萃分析


目的 评估使用迷幻药和艾司西酞普兰口服单药治疗抑郁症状患者的比较疗效和可接受性，同时考虑到盲法不成功导致高估疗效的可能性。设计 系统评价和贝叶斯网络荟萃分析。从数据库建库到 2023 年 10 月 12 日的数据来源 Medline、Cochrane 对照试验中心注册库、Embase、PsycINFO、ClinicalTrial.gov 和世界卫生组织国际临床试验注册平台。选择研究的资格标准 关于迷幻药或艾司西酞普兰治疗有抑郁症状的成人的随机对照试验。符合条件的迷幻药（3,4-亚甲二氧基甲基苯丙胺（称为MDMA）、麦角酸二乙胺（称为LSD）、裸盖菇素或死藤水）的随机对照试验需要口服单药治疗，不同时使用抗抑郁药。资料提取和综合 主要结局是抑郁症的变化，通过 17 项汉密尔顿抑郁评定量表测量。次要结局均为原因停药和严重不良事件。严重不良事件是导致一系列负面健康结果中任何一种的事件，包括死亡、入院、严重或持续丧失行为能力、先天性出生缺陷或异常以及自杀未遂。使用贝叶斯框架内的随机效应模型汇总数据。为避免估计偏倚，将安慰剂反应分为迷幻药和抗抑郁药试验。结果 迷幻药试验中的安慰剂反应低于艾司西酞普兰的抗抑郁试验 （平均差 -3.90 （95% 可信区间 -7.10 至 -0.96））。 尽管在迷幻药试验中大多数迷幻药优于安慰剂，但在艾司西酞普兰的抗抑郁试验中，只有高剂量裸盖菇素优于安慰剂（平均差 6.45 （3.19 至 9.41））。然而，当参考组从迷幻药试验中的安慰剂反应转变为抗抑郁药试验时，高剂量裸盖菇素的效应量（标准化均数差）从大（0.88）下降到小（0.31）。高剂量裸盖菇素的相对效果大于艾司西酞普兰，为 10 mg （4.66 （95% 可信区间 1.36 至 7.74）） 和 20 mg （4.69 （1.64 至 7.54））。与安慰剂相比，所有干预措施均与更高的全因停药或严重不良事件相关。结论 在现有的抑郁症状迷幻药治疗中，在抗抑郁药试验中，接受高剂量裸盖菇素治疗的患者表现出比安慰剂治疗的患者更好的反应，但效应量较小。系统综述注册 PROSPERO， CRD42023469014.支持本研究结果的数据可应合理要求从通讯作者 （C-SL） 处获得。