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Esketamine and Psilocybin—The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review

Dominika Psiuk, Emilia Magdalena Nowak, Natalia Dycha, Urszula Łopuszańska, Jacek Kurzepa, Marzena Samardakiewicz

International Journal of Molecular Sciences September 28, 2022 DOI: 10.3390/ijms231911450 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Interventions Esketamine Psilocybin
Topics Depression Esketamine Psilocybin Ketamine
Keywords Psychedelics hallucinogens Entheogens Psychoactive drugs Mood disorder treatment Therapeutic advances Novel treatments
Citations 36
Key findings Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and may be considered as novel antidepressant agents.

Abstract

This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment—psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin’s antidepressive effects occurred one day after intake and after 6–7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin’s effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future.

Comparable studies

Other systematic reviews and meta-analyses on psilocybin for depression, most cited first.

Study Year Design Participants
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188
The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression 2020 Meta-analysis n = 117
Psychedelics in the treatment of unipolar mood disorders: a systematic review Patients with broadly defined unipolar mood disorders 2016 Systematic review n = 423
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... 2023 Systematic review with meta-analysis n = 14
Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Patients with life-threatening diseases and symptoms of anxiety or depression 2018 Systematic review n = 445

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