This post hoc analysis of a recent clinical trial comparing psilocybin to escitalopram with psychological support for depression (MDD) found that discontinuing SSRIs/SNRIs prior to psilocybin treatment led to reduced treatment effects on depression severity measures. However, there were no observed effects on the acute psychedelic experience. The study suggests that discontinuation of SSRIs/SNRIs before psilocybin treatment might impact treatment response.

Abstract of Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression

“Background: 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.

Aims: 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.

Methods: 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.

Conclusion: 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.”

Authors: David Erritzoe, Tommaso Barba, Meg J. Spriggs, Fernando E. Rosas, David J. Nutt & Robin L. Carhart-Harris

Summary of Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression

Introduction

Major depressive disorder (MDD) is one of the most economically and socially burdensome diseases worldwide. Psilocybin has recently been investigated as a possible alternative treatment option for MDD, through agonism of serotonin 2A receptors (5-HT2AR).

A double-blind randomized control trial comparing psilocybin to escitalopram in individuals diagnosed with MDD found that psilocybin elicited nominally greater reductions in depression symptoms than escitalopram, but outperformed escitalopram on all secondary outcome measures.

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Find this paper

Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression

https://doi.org/10.1177/02698811241237870

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Cite this paper (APA)

Erritzoe, D., Barba, T., Spriggs, M. J., Rosas, F. E., Nutt, D. J., & Carhart-Harris, R. (2024). Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression. Journal of Psychopharmacology, 02698811241237870.

Study details

Compounds studied
Psilocybin

Topics studied
Depression

Study characteristics
Original Re-analysis Placebo-Controlled Active Placebo Double-Blind Randomized Re-analysis

Participants
59 Humans

Institutes

Institutes associated with this publication

Imperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 25 mg | 2x

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