Background: Treatment-resistant depression (TRD), a clinical subtype of major depressive disorder (MDD), is associated with greater severity and functional impairment, representing a significant challenge in psychiatric care. Recent studies suggest that the use of psychedelics can provide rapid and substantial improvement in the severity of depressive symptoms. Therefore, the aim of this systematic review is to evaluate and synthesize the evidence on the efficacy of psychedelics in the treatment of TRD. Methods: Studies were included if they enrolled participants diagnosed with TRD, used scales to assess depression severity, reported effect sizes or provided metrics for calculating effect sizes of the intervention, and involved single-blind, double-blind, or open-label trials, including single-arm studies. Results: Fifteen articles were included in this systematic review, 10 of which were randomized double-blind controlled trials (RCTs) and 5 open-label clinical trials. All studies were summarized and analyzed, providing a current overview of the scientific literature on the therapeutic potential of typical and atypical psychedelics in TRD. Conclusions: The use of psychedelics in the treatment of treatment-resistant depression represents an alternative and complementary therapeutic approach to traditional treatments, suggesting efficacy across different classes of these substances.
Horato et al. (2026) studied this question.