Efficacy, Safety, and Tolerability of Psychedelics in Treatment-Resistant Depression (TRD)

About 30% of individuals with major depressive disorder do not respond to first-line antidepressant treatments.

• Treatment-resistant depression (TRD) is characterized by a lack of response to two or more different antidepressant treatments.
• Recent research has led to the development of new medications for TRD using both serotonergic and glutamatergic psychedelics.
• Psychedelics like psilocybin and ketamine may produce rapid and long-lasting antidepressant effects beyond their immediate biological presence.
• The clinical development of psilocybin and esketamine faces challenges in using effective placebo controls due to their psychoactive effects.
• Intranasal esketamine has been approved for TRD, while psilocybin has also shown promising results in clinical settings.
• Both psilocybin and esketamine generally exhibit acceptable levels of adverse effects and tolerability in the studied dose ranges.

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