This post hoc analysis (n=233) of a Phase II RCT investigates the impact of recent antidepressant discontinuation (n=156) on the efficacy of psilocybin in treating treatment-resistant depression (TRD). The study compares outcomes between participants who discontinued antidepressants during screening and those who entered the trial free of these medications, finding no significant relationship between antidepressant discontinuation and worsening depression severity or compromised psilocybin treatment efficacy.
Abstract of The Impact of Antidepressant Discontinuation Prior to Treatment with Psilocybin for Treatment-Resistant Depression
“It has been suggested that the recent use and discontinuation of antidepressant drugs compromises the action of psilocybin. As evidence is only available from small or uncontrolled samples, this post hoc analysis investigated this using data from the largest, phase II, randomized controlled trial of psilocybin treatment to date. Data from 233 participants with treatment-resistant depression (TRD) who received 25 mg, 10 mg, or 1 mg of investigational drug COMP360 psilocybin (a proprietary, pharmaceutical-grade synthetic psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.), administered with psychological support, were compared for groups of participants who either discontinued one or more antidepressant drugs during screening or entered the trial antidepressant drug free. Measures of depression symptom severity change during the antidepressant drug discontinuation period, baseline suicidality, acute subjective psychedelic effects, and the study’s primary endpoint (change in depression symptom severity between Baseline and Week 3) are described for both groups. Antidepressant drug discontinuation was not related to worsening of depression severity before Baseline. Suicidality was comparable between groups at Baseline. Psilocybin treatment efficacy and the subjective psychedelic experience did not appear to be compromised by antidepressant drug discontinuation. Thus, it does not limit the feasibility of psilocybin treatment for the future. These findings also support the overall homogeneity of our findings with psilocybin treatment as a monotherapy for TRD. The prior contradictory reports may come to appear misleading.“
Authors: Lindsey Marwood, Megan Croal, Sunil Mistry, Hollie Simmons, Joyce Tsai, Matthew B. Young, & Guy M. Goodwin
Summary of The Impact of Antidepressant Discontinuation Prior to Treatment with Psilocybin for Treatment-Resistant Depression
The introduction of the article discusses the potential of psilocybin, a psychedelic compound found in certain mushrooms, as a treatment for treatment-resistant depression (TRD). The authors highlight the increasing interest in psychedelics for mental health treatment, particularly in cases where traditional antidepressants have failed. Psilocybin acts primarily on serotonin receptors in the brain, which are crucial for mood regulation. The introduction also references the ongoing debate about whether recent use of antidepressants affects the efficacy of psilocybin treatments.
The authors denote that prior studies have suggested a possible compromise in the psychedelic experience when individuals have recently discontinued or used antidepressant medications. However, many of these studies were limited in scope, often relying on small or uncontrolled samples. Therefore, this research aims to fill the gap by analysing data from a large, Phase II, randomised controlled trial of psilocybin, making it one of the most comprehensive investigations into this area to date.
The significance of this study lies in its focus on a well-defined population of participants suffering from TRD, as well as its methodological rigour. By comparing the effects of psilocybin on individuals who discontinued antidepressants with those who entered the trial drug-free, the authors seek to clarify the relationship between antidepressant discontinuation and the efficacy of psilocybin treatment.
Methods
Trial Oversight
Find this paper
https://doi.org/10.1016/j.jpsychires.2024.10.009
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Cite this paper (APA)
Marwood, L., Croal, M., Mistry, S., Simmons, H., Tsai, J., Young, M. B., & Goodwin, G. M. (2024). The Impact of Antidepressant Discontinuation Prior to Treatment with Psilocybin for Treatment-Resistant Depression. Journal of Psychiatric Research.
Study details
Compounds studied
Psilocybin
Topics studied
Treatment-Resistant Depression
Depression
Study characteristics
Original Re-analysis
Placebo-Controlled
Active Placebo
Double-Blind
Randomized
Participants
233
Humans
Compound Details
The psychedelics given at which dose and how many times
Psilocybin 1 - 25mg | 1x
Linked Research Papers
Notable research papers that build on or are influenced by this paper
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major DepressionThis double-blind active-placebo controlled trial (n=233) tested the effect of a single dose of psilocybin (25/10/1mg) with supportive therapy for treatment-resistant depression. The primary endpoint at three weeks finds a significant reduction in depressive symptoms (MADRS, 12-point drop from baseline of 32) that was significantly greater in the 25mg group vs the 1mg (placebo) group (6.6 points larger drop). The response (>50% drop in MADRS score) in the 25mg group dropped from 37% at 3 weeks to 20% at 12 weeks.
Linked Clinical Trial
The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant DepressionThe Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression - a dose-ranging study.