Psilocybin shows large, rapid, and persistent clinical effects in treating resistant or end-of-life depression, with good tolerance and mild side effects limited to a few hours after dosing. However, studies to date have had small sample sizes, and one clinical trial against escitalopram did not show significant superiority of psilocybin on the main outcome. The neurobiological mechanisms, which differ from those of SSRI antidepressants, remain mostly unknown. Psilocybin is a promising alternative, but further research with larger samples and comparisons to standard treatments is needed.
In a naturalistic study across four Madrid hospitals, 55% of 65 patients with treatment-resistant depression who received esketamine as an augmentation treatment achieved remission over follow-up. Among those who completed the standard protocol, remission rates rose to 67%, and to 70% for those receiving more than 19 administrations. Remission was associated with completing the standard protocol and with the absence of dissociative symptoms. Receiving more than 19 esketamine administrations increased the odds of remission. Adverse effects did not affect treatment continuation.