The Therapeutic Potential of Psychedelics for Treatment-resistant Depression: Reality or Hallucination? A Systematic Review.
Natia Horato, Felipe Dalvi-Garcia, Pablo E P Dutra, Antonio E Nardi
Journal of clinical psychopharmacology January 12, 2026 DOI: 10.1097/JCP.0000000000002122 via PubMed
Summary
AI-generated from the abstractA systematic review of 15 studies (10 randomized double-blind controlled trials and 5 open-label trials) examined the efficacy of psychedelics for treatment-resistant depression (TRD), a severe subtype of major depressive disorder. The review suggests that both typical and atypical psychedelics can provide rapid and substantial improvement in depressive symptoms, representing an alternative and complementary therapeutic approach to traditional treatments for TRD.
Study at a glance
| Characteristics | Systematic review Randomized Double-blind Open-label Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Participants diagnosed with treatment-resistant depression (TRD) |
| Topics | Depression Psychedelic-assisted therapy |
| Keywords | Psychedelics |
| Citations | 1 |
| Key finding | The use of psychedelics in the treatment of treatment-resistant depression suggests efficacy across different classes of these substances. |
Abstract
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. 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. 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. 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.