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Abstract
Major Depressive Disorder (MDD) has compromised neurobiological, cognitive and behavioral aspects. Around a third of people with MDD progress to Treatment Resistant Depression (TRD), characterized by a failure to respond to antidepressants of adequate dose and duration. Therefore, first-line treatments, such as Selective Serotonin Reuptake Inhibitors (SSRIs), show limitations such as resistance, risk of relapse and low adherence. New treatments such as Psilocybin-Assisted Psychotherapy (PAP) are being studied in order to achieve rapid and sustained effects. Given this panorama, the aim of this article was to gather evidence on the use of PAP for the treatment of individuals with MDD. To this end, a systematic review, registered in PROSPERO under the number CRD420251120011, was carried out in the MEDLINE, PubMed, Scopus, CENTRAL and EMBASE databases, which resulted in the inclusion of 10 Randomized Clinical Trials (RCTs) and a total of 848 participants. As a result, the clinical trials showed that treatment with psilocybin, from week 2 onwards, reduced scores on the depression scale and lead to improvements in depressive symptoms. In addition, remission of these symptoms was observed, as well as sustained responses in individuals who received treatment with psilocybin psilocybin compared to placebo. In conclusion, although PAP has been shown to be effective in treating MDD, the studies have significant methodological limitations, such as limited sample composition, lack of active comparators, and limited short-term follow-up. Therefore, further research is needed to strengthen methodological validity and generate more robust evidence.
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