Psilocybin in the Treatment of Depressive Disorders: Clinical Evidence and Its Potential to Address the Global Mental Health Crisis - A Review

Introduction: Depressive disorders are one of the greatest public health challenges worldwide, affecting up to 16% of the population over a lifetime and significantly impacting quality of life, disability, and premature mortality. Major depressive disorder (MDD) is a leading cause of disability, despite the availability of numerous treatment options. In 20–50% of patients, traditional pharmacotherapy and psychotherapy become ineffective, leading to a diagnosis of treatment-resistant depression (TRD). Objective: The objective of this study was to provide a thorough assessment of current research findings evaluating the efficacy and safety of psilocybin-assisted therapy (PAT) in patients with MDD and TRD, with particular emphasis on rapid antidepressant effects and long-term therapeutic potential. Methods: A literature review was conducted in the PubMed and Google Scholar databases. Keywords related to psilocybin, depression, treatment-resistant depression, and psychedelic-assisted therapy were used. Results: Psilocybin-assisted psychotherapy is a promising alternative for the treatment of MDD, TRD, and secondary depression. Compared to traditional antidepressants, PAT is characterized by a faster onset of action, symptom reduction often occurs as early as the first week after starting therapy, and the achieved results may persist long-term for up to 6–12 months. In addition, many patients showed improvement in anhedonia, anxiety, and overall psychosocial functioning. Conclusions: Psilocybin represents a promising therapeutic alternative for patients with severe depression and TRD, offering rapid and lasting antidepressant effects. Its use could significantly change the approach to treating depression, particularly in cases resistant to standard therapies.