英国格林威治大学Trevor Thompson团队比较了迷幻药和艾司西酞普兰口服单一疗法治疗抑郁症状患者的疗效。2024年8月21日出版的《英国医学杂志》发表了这项成果。

为了评估使用迷幻药和艾司西酞普兰口服单一疗法在抑郁症状患者中的有效性和可接受性，考虑到由于盲法不成功而高估疗效的可能性，研究组检索了对照试验中央登记册、Embase、PsycINFO、ClinicalTrial.gov和世界卫生组织的国际临床试验注册平台中从建库到2023年10月12日的相关文献，筛选出对抑郁症状成年人进行迷幻药或艾司西酞普兰的随机对照试验，进行了一项系统综述和贝叶斯网络荟萃分析。符合条件的迷幻药（3,4-亚甲基二氧基甲基苯丙胺（MDMA）、麦角酸二乙胺（LSD）、裸盖菇素或死藤水）随机对照试验需要口服单一疗法，不同时使用抗抑郁药。

主要结局是抑郁症的变化，通过17项汉密尔顿抑郁量表进行测量。次要结局为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、严重或持续丧失能力、先天性出生缺陷或异常以及自杀企图。在贝叶斯框架内使用随机效应模型对数据进行汇总。为了避免估计偏差，在迷幻药和抗抑郁药试验之间对安慰剂反应进行了区分。

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（平均差异-3.90（95%可信区间-7.10至-0.96））。尽管在迷幻药试验中，大多数迷幻药都优于安慰剂，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（平均差异6.45（3.19至9.41））。然而，当对照组从迷幻药试验中的安慰剂反应变为抗抑郁药试验时，高剂量裸盖菇素的效应（标准化平均差异）从大（0.88）减小（0.31）。高剂量裸盖菇素在10mg（4.66（95%可信区间1.36至7.74））和20mg（4.69（1.64至7.54））时的相对效果大于艾司西酞普兰。与安慰剂相比，这些干预措施均与更高的全因停药或严重不良事件无关。

研究结果表明，在治疗抑郁症状的现有迷幻药物中，在抗抑郁试验中，接受高剂量裸盖菇素治疗的患者比接受安慰剂治疗的患者表现出更好的反应，但疗效很轻微。

附：英文原文

Title: Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis

Author: Tien-Wei Hsu, Chia-Kuang Tsai, Yu-Chen Kao, Trevor Thompson, Andre F Carvalho, Fu-Chi Yang, Ping-Tao Tseng, Chih-Wei Hsu, Chia-Ling Yu, Yu-Kang Tu, Chih-Sung Liang

Issue&Volume: 2024/08/21

Abstract:

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.

DOI: 10.1136/bmj-2023-078607

Source: https://www.bmj.com/content/386/bmj-2023-078607