PDF(Pubmed)
Abstract：
To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.
Systematic review and meta-analysis.
Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.
Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges\' g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies\' sample sizes. Study quality was appraised using Cochrane\'s Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.
Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.
Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges\' g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges\' g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating.
Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant.
PROSPERO CRD42023388065.
Systematic review and meta-analysis.
Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.
Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges\' g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies\' sample sizes. Study quality was appraised using Cochrane\'s Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.
Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.
Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges\' g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges\' g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating.
Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant.
PROSPERO CRD42023388065.
摘要：
目的：确定与安慰剂或非精神活性药物相比，psilocybin作为抗抑郁药的疗效。
方法：系统评价和荟萃分析。
方法：已发表文献的五个电子数据库（Cochrane中央对照试验登记册，Medline,Embase,科学引文索引和会议论文集引文索引，和PsycInfo）和四个未发表和国际文献数据库（ClinicalTrials.gov，世卫组织国际临床试验注册平台，ProQuest论文和论文全球，和PsycEXTRA），和手动搜索参考列表，会议记录,和摘要。
■提取了有关潜在治疗效果调节因素的信息，包括抑郁症类型（原发性或继发性），以前使用过迷幻药，psilocybin剂量,结果测量类型(临床医生评级或自我报告)，和个人特征(例如，年龄,性)。数据使用随机效应荟萃分析模型进行综合，通过亚组分析和回归研究观察到的异质性和协变量的影响。对冲被用作治疗效果大小的量度，考虑小样本效应和纳入研究样本量之间的实质性差异。使用Cochrane的偏差风险2工具评估研究质量，使用GRADE指南评估汇总证据的质量.
方法：使用经过验证的临床医生评分或自我报告量表，对具有临床显著抑郁症状和症状变化的成人进行独立治疗的随机试验。如果在实验和对照条件下都存在心理治疗成分，则包括指导性心理治疗的研究。患有抑郁症的参与者，无论合并症如何（例如，癌症）符合条件。
结果：对436名参与者（228名女性参与者）的Meta分析，平均年龄36-60岁,在纳入的9项研究中,有7项研究显示,与对照治疗相比,裸盖菇素(Hedges\'g=1.64,95%置信区间(CI)0.55~2.73,P<0.001)对抑郁评分的变化有显著益处.亚组分析和分析显示具有继发性抑郁(对冲=3.25,95%CI0.97至5.53),用贝克抑郁量表(3.25、0.97至5.53)等自我报告抑郁量表进行评估，年龄和既往使用迷幻药(回归系数分别为0.16,95%CI0.08~0.24和4.2,1.5~6.9)与症状改善程度相关.所有研究的偏倚风险都很低，但是基线指标的变化与高度异质性和小研究偏差的统计学显著风险相关，导致证据评级的确定性较低。
结论：在继发性抑郁症患者中，psilocybin的治疗效果明显更大，当使用自我报告量表来测量抑郁症的症状时，以及参与者以前使用过迷幻药。因此，需要进一步的研究来描绘预期效应的影响，缓和因素，和治疗递送对psilocybin作为抗抑郁药的疗效。
背景：PROSPEROCRD42023388065。
方法：系统评价和荟萃分析。
方法：已发表文献的五个电子数据库（Cochrane中央对照试验登记册，Medline,Embase,科学引文索引和会议论文集引文索引，和PsycInfo）和四个未发表和国际文献数据库（ClinicalTrials.gov，世卫组织国际临床试验注册平台，ProQuest论文和论文全球，和PsycEXTRA），和手动搜索参考列表，会议记录,和摘要。
■提取了有关潜在治疗效果调节因素的信息，包括抑郁症类型（原发性或继发性），以前使用过迷幻药，psilocybin剂量,结果测量类型(临床医生评级或自我报告)，和个人特征(例如，年龄,性)。数据使用随机效应荟萃分析模型进行综合，通过亚组分析和回归研究观察到的异质性和协变量的影响。对冲被用作治疗效果大小的量度，考虑小样本效应和纳入研究样本量之间的实质性差异。使用Cochrane的偏差风险2工具评估研究质量，使用GRADE指南评估汇总证据的质量.
方法：使用经过验证的临床医生评分或自我报告量表，对具有临床显著抑郁症状和症状变化的成人进行独立治疗的随机试验。如果在实验和对照条件下都存在心理治疗成分，则包括指导性心理治疗的研究。患有抑郁症的参与者，无论合并症如何（例如，癌症）符合条件。
结果：对436名参与者（228名女性参与者）的Meta分析，平均年龄36-60岁,在纳入的9项研究中,有7项研究显示,与对照治疗相比,裸盖菇素(Hedges\'g=1.64,95%置信区间(CI)0.55~2.73,P<0.001)对抑郁评分的变化有显著益处.亚组分析和分析显示具有继发性抑郁(对冲=3.25,95%CI0.97至5.53),用贝克抑郁量表(3.25、0.97至5.53)等自我报告抑郁量表进行评估，年龄和既往使用迷幻药(回归系数分别为0.16,95%CI0.08~0.24和4.2,1.5~6.9)与症状改善程度相关.所有研究的偏倚风险都很低，但是基线指标的变化与高度异质性和小研究偏差的统计学显著风险相关，导致证据评级的确定性较低。
结论：在继发性抑郁症患者中，psilocybin的治疗效果明显更大，当使用自我报告量表来测量抑郁症的症状时，以及参与者以前使用过迷幻药。因此，需要进一步的研究来描绘预期效应的影响，缓和因素，和治疗递送对psilocybin作为抗抑郁药的疗效。
背景：PROSPEROCRD42023388065。
