Division of Psychiatry, Department Brain Sciences, Centre for Psychedelic Research, Imperial College London, London, UK.
Department of Informatics, University of Sussex, Brighton, UK.
J Psychopharmacol. 2024 May;38(5):458-470. doi: 10.1177/02698811241237870. Epub 2024 Mar 22.
There is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling.
Using data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes.
Exploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored.
RESULTS/OUTCOMES: In the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found.
Discontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.
越来越多的证据表明迷幻药裸盖菇素对重度抑郁症有治疗作用。然而，由于缺乏将裸盖菇素与选择性 5-羟色胺再摄取抑制剂（SSRIs）和 5-羟色胺去甲肾上腺素再摄取抑制剂（SNRIs）联合使用的安全性数据，并且担心在疗效上可能存在负面相互作用，因此通常要求参加迷幻药物试验的参与者在入组前停止使用 SNRI/SNRI。
利用最近一项临床试验的数据，该试验检查了迷幻药物裸盖菇素（P）与大约 20 小时的心理支持相结合，与 6 周（每日）的 SSRI 依地普仑加匹配的心理支持治疗重度抑郁症的比较疗效，我们探讨了在研究入组前停止使用 SSRIs/SNRIs 对研究结果的影响。
使用线性混合效应模型进行探索性事后分析，以调查各种已验证的抑郁症状严重程度量表和幸福感的停药效果。还探讨了 SSRIs/SNRIs 停药对急性迷幻体验的影响。
结果/结论：在裸盖菇素组中，与未用药患者相比，SSRIs/SNRIs 停药者在所有结局测量上的治疗效果均降低。然而，没有发现停药对急性迷幻体验测量的影响。
在接受裸盖菇素治疗之前停止使用 SSRIs/SNRIs 可能会降低治疗反应；然而，由于我们在试验中没有测试 SSRIs/SNRI 的继续使用，我们不能推断出这种因果关系。此外，分析的探索性质使得它们具有假设生成的性质，而不是确证性的。迫切需要进行一项对照试验，以比较在接受裸盖菇素治疗之前停止和继续使用 SSRIs/SNRI。
