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

A systematic review of 12 studies examined two psychoactive compounds, psilocybin and esketamine, for treating depression. Esketamine, a laboratory-made substance, showed significant reduction in depressive symptoms and suicidal ideation shortly after intake and after one month, compared to baseline and standard antidepressants. Psilocybin, a naturally occurring psychedelic, produced antidepressant effects one day after intake and after 6–7 weeks, with benefits lasting up to 6 or 8 months. One study suggested psilocybin's effects are comparable to and may be superior to escitalopram. Both compounds demonstrated rapid and sustained effects, indicating potential as novel antidepressant agents after addressing limitations.

Study at a glance

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.