Concomitant use of antidepressants and classic psychedelics: A scoping review

Summary & key facts

The authors gathered and summarized all human studies they could find about people taking regular antidepressants at the same time as classic psychedelics. They looked through major medical databases up to March 2025 and included 18 studies. Overall, the studies suggest that using antidepressants together with classic psychedelics appears mostly safe and often tolerable, especially with psilocybin, and some studies even saw improvements in depression symptoms. However, the evidence is limited and mixed, so the authors call for better, carefully controlled trials before changing current medical rules.

Key facts:

• The paper is a scoping review, which means the researchers collected and summarized all existing human studies on taking antidepressants and classic psychedelics together.
• They searched major medical databases up to March 3, 2025 and included 18 studies in their summary.
• Across these studies, combined use of antidepressants and classic psychedelics was generally reported as safe and tolerable.
• The review did not find an increased risk of serotonin syndrome, a rare but serious reaction, especially when psilocybin was used.
• Some studies reported meaningful improvements in depression and other mental health symptoms when psychedelics were used while people stayed on antidepressants.
• A few studies suggested that antidepressants might reduce the acute subjective effects of psychedelics (the immediate ‘trip’ experience), but this was not seen in all studies.
• The authors note that asking people to stop antidepressants before psychedelic treatment can be a big burden and might worsen depression or raise suicidal thoughts for some people.
• Because the existing studies have important gaps and limits, the authors say we need higher-quality randomized, double-blind, placebo-controlled trials before changing clinical rules about stopping antidepressants.

Abstract

Classic psychedelics are increasingly studied as potential treatments for different psychiatric disorders. Current research protocols often require patients to discontinue antidepressants (ADs) for at least 2 weeks before psychedelic administration to decrease the risk of serotonin syndrome and limit their effect on efficacy and the acute subjective effects of psychedelics. Moreover, the discontinuation of ADs represents a significant burden to patients that could also worsen their depression status and increase suicidal ideation. Together, this suggests that the general recommendation for AD discontinuation might be unnecessary and even detrimental to the therapeutic efficacy of psychedelics. In this scoping review, we summarise the existing literature on the concomitant use of conventional ADs with classic psychedelics in humans with the aims to assess safety, tolerability, efficacy, and subjective effects. Following PRISMA-ScR guidelines, we searched MEDLINE, Embase, and Scopus databases to retrieve relevant literature from inception to March 3, 2025. Data were systematically charted from included studies. We included 18 studies and found that the concomitant use of ADs and classic psychedelics is generally safe and tolerable, with no increased risk of serotonin syndrome, particularly for psilocybin. Some studies reported significant improvements in depression and other mental health symptoms. While some evidence indicates a potential attenuation of acute subjective psychedelic effects, this was not observed in all studies. Accordingly, we conclude that the use of ADs can be maintained to enhance patient access to psychedelic treatments and avoid the risk of AD discontinuation syndrome. Finally, this review highlights limitations and several knowledge gaps in the current literature that need to be addressed in future randomized double-blind, placebo-controlled trials.

Topics

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Clinical psychology Concomitant Depression (economics) Discontinuation Injury prevention Intensive care medicine Major depressive episode Medicine MEDLINE Mental health Poison control Psychiatry Psychology Risk assessment Scopus Suicidal ideation Suicide prevention

Substances

Psilocybin

Conditions & symptoms

Depression Sadness or low mood