PSYCHEDELIC-ASSISTED PSYCHOTHERAPY IN MAJOR DEPRESSIVE DISORDER: EVIDENCE ON EFFICACY, SAFETY AND SUSTAINABILITY OF THERAPEUTIC RESPONSE

Abstract

Major depressive disorder is an important public health problem characterized by high prevalence, recurrence, functional impairment, and insufficient response to conventional treatments in a substantial proportion of patients. In this context, psychedelic-assisted psychotherapy, particularly psilocybin-assisted therapy, has received increasing scientific attention because of its potential to produce rapid antidepressant responses after a limited number of administrations. This study aimed to analyze the available evidence regarding the efficacy, safety, and sustainability of therapeutic response associated with psychedelic-assisted psychotherapy in major depressive disorder. A narrative literature review was conducted using PubMed/MEDLINE, Embase, Cochrane Library, and SciELO, with search terms related to psilocybin, psychedelic-assisted psychotherapy, major depressive disorder, treatment-resistant depression, safety, and therapeutic response. Thirty-two scientific studies and documents were included in the final synthesis, with priority given to publications from 2020 to 2026. The findings demonstrated significant reductions in depressive symptoms across several clinical trials, with effects observed within the first days after intervention and maintained for variable periods. Recent meta-analyses also reported higher response and remission rates compared with control interventions. The most frequent adverse events were generally transient and included headache, nausea, dizziness, and acute cardiovascular changes, although rigorous participant selection remains essential. Follow-up studies suggest that therapeutic benefits may persist for several months, but available evidence remains limited and heterogeneous. In conclusion, psilocybin-assisted psychotherapy shows promising results, but clinical implementation requires standardized protocols, appropriate monitoring, careful patient selection, and longer-term studies.