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、麦角酰二乙胺、3,4-亚甲二氧基甲基苯丙胺、死藤水和艾司西酞普兰治疗抑郁症状的口服单药比较：系统评价和贝叶斯网络荟萃分析


目的 考虑到因盲法不成功而可能高估疗效的可能性，评估使用致幻剂和艾司西酞普兰口服单一疗法治疗抑郁症状患者的比较有效性和可接受性。设计系统回顾和贝叶斯网络荟萃分析。数据来源 Medline、Cochrane 对照试验中央注册库、Embase、PsycINFO、ClinicalTrial.gov 和世界卫生组织国际临床试验注册平台（从数据库建立到 2023 年 10 月 12 日）。 选择研究的资格标准 关于成人迷幻药或艾司西酞普兰的随机对照试验有抑郁症状。符合条件的致幻剂（3,4-亚甲二氧基甲基苯丙胺（MDMA）、麦角酰二乙胺（LSD）、裸盖菇素或死藤水）随机对照试验需要口服单一疗法，不需同时使用抗抑郁药。数据提取和综合主要结果是抑郁症的变化，通过 17 项汉密尔顿抑郁评定量表进行测量。次要结局是全因停药和严重不良事件。严重不良事件是指导致一系列负面健康结果的事件，包括死亡、入院、严重或持续丧失工作能力、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集数据。为了避免估计偏差，迷幻药和抗抑郁药试验中的安慰剂反应有所不同。结果迷幻药试验中的安慰剂反应低于艾司西酞普兰抗抑郁试验中的反应（平均差-3.90（95%可信区间-7.10至-0.96））。 尽管在迷幻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，当参考组从迷幻试验中的安慰剂反应变为抗抑郁试验时，高剂量裸盖菇素的效应大小（标准化平均差）从大（0.88）下降到小（0.31）。高剂量裸盖菇素的相对效应大于艾司西酞普兰，剂量为 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，所有干预措施都不会导致更高的全因停药或严重不良事件。结论 在抗抑郁试验中，在可用的迷幻药物治疗抑郁症状中，大剂量裸盖菇素治疗的患者比安慰剂治疗的患者表现出更好的反应，但效果较小。系统审评注册PROSPERO，CRD42023469014。支持本研究结果的数据可根据合理要求从通讯作者 (C-SL) 处获得。