{"title":"比较西洛宾、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对抑郁症状的口服单一疗法:系统综述和贝叶斯网络荟萃分析。","authors":"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","doi":"10.1136/bmj-2023-078607","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>Systematic review and Bayesian network meta-analysis.</p><p><strong>Data sources: </strong>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.</p><p><strong>Eligibility criteria for selecting studies: </strong>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.</p><p><strong>Data extraction and synthesis: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Systematic review registration: </strong>PROSPERO, CRD42023469014.</p>","PeriodicalId":9201,"journal":{"name":"BMJ : British Medical Journal","volume":null,"pages":null},"PeriodicalIF":105.7000,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337322/pdf/","citationCount":"0","resultStr":"{\"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.\",\"authors\":\"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\",\"doi\":\"10.1136/bmj-2023-078607\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>Systematic review and Bayesian network meta-analysis.</p><p><strong>Data sources: </strong>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.</p><p><strong>Eligibility criteria for selecting studies: </strong>Randomised controlled trials on psychedelics or escitalopram in adults with depressive symptoms. 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引用次数: 0
摘要
目的考虑到盲法不成功可能导致疗效被高估,对抑郁症状患者使用迷幻药和艾司西酞普兰口服单一疗法的有效性和可接受性进行比较评估:设计:系统综述和贝叶斯网络荟萃分析: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.选择研究的资格标准:针对成人抑郁症状患者的迷幻药或艾司西酞普兰随机对照试验。符合条件的迷幻药(3,4-亚甲二氧基甲基苯丙胺(MDMA)、麦角酰二乙胺(LSD)、西洛西宾或死藤水)随机对照试验要求口服单药治疗,且不同时使用抗抑郁药:主要结果是抑郁程度的变化,采用 17 项汉密尔顿抑郁评分量表进行测量。次要结果为所有原因导致的停药和严重不良事件。严重不良事件是指导致一系列不良健康后果的事件,包括死亡、入院治疗、严重或持续丧失工作能力、先天性缺陷或异常以及自杀未遂。数据采用贝叶斯框架内的随机效应模型进行汇总。为避免估计偏差,安慰剂反应在迷幻药试验和抗抑郁药试验之间进行了区分: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中的安慰剂反应(平均差异为-3.90(95%可信区间为-7.10至-0.96))。虽然在迷幻药试验中,大多数迷幻药的疗效优于安慰剂,但在艾司西酞普兰的抗抑郁试验中,只有大剂量的迷幻药的疗效优于安慰剂(平均差异为6.45(3.19至9.41))。然而,当参考臂从迷幻药试验中的安慰剂反应变为抗抑郁试验中的安慰剂反应时,大剂量迷幻药的效应大小(标准化平均差)从大(0.88)降至小(0.31)。10毫克(4.66(95%可信区间为1.36至7.74))和20毫克(4.69(1.64至7.54))大剂量西洛滨的相对效应大于艾司西酞普兰。与安慰剂相比,所有干预措施的停药率或严重不良事件发生率都不高:结论:在现有的治疗抑郁症状的迷幻药中,在抗抑郁试验中,接受大剂量迷幻药治疗的患者比接受安慰剂治疗的患者表现出更好的反应,但效果很小:prospero,CRD42023469014。
Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis.
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.
期刊介绍:
The BMJ (British Medical Journal) is an international peer-reviewed medical journal with a "continuous publication" model, where articles are published on bmj.com before appearing in the print journal. The website is updated daily with the latest original research, education, news, and comment articles, along with podcasts, videos, and blogs. The BMJ's editorial team is primarily located in London, with additional editors in Europe, the US, and India.