Psilocybin for major depressive disorder: An updated systematic review and meta-analysis of randomized clinical trials
Sepehr Aghajanian, Arman Shafiee, Samira Parvizi Omran, Aida Rezaei Nejad, Kyana Jafarabady, Omid Kohandel Gargari, Shahryar Rajai, Ida Mohammadi, Touran Bahrami Babaheidari, Mahmood Bakhtiyari
Journal of Psychopharmacology October 31, 2024 DOI: 10.1177/02698811241287542 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Topics | Depression Psilocybin |
| Keywords | Psychedelics hallucinogens Entheogens Psychoactive drugs Psychological wellbeing Behavioral health Antidepressant therapy Mood disorder treatment |
| Citations | 12 |
| Key findings | Psilocybin plus supportive therapy yields a large reduction in depressive symptoms compared to baseline and placebo, and the effect persists over time. |
Abstract
Background: Due to the unsatisfactory therapeutic effects of current antidepressants, research has been launched into alternative treatment approaches, such as the administration of psychedelics. Psilocybin, a classic hallucinogen, has been shown to exert considerable positive influence on depression symptoms through its serotonergic and glutamatergic effects. This systematic review and meta-analysis aimed to evaluate the effectiveness of psilocybin in treating depression.
Methods: A comprehensive search of Medline (via PubMed) and the Cochrane Library databases was conducted to identify relevant studies. Inclusion criteria were applied to select studies that investigated the therapeutic impact of psilocybin on depression. A mixed-effects multi-level model was used to estimate the overall effect size. Effectiveness over time was also investigated as a secondary analysis.
Results: The results of the primary analysis revealed a large and clinically observable reduction (SMC: −1.24, 95%CI: −1.83 to −0.65, I 2 level2 = 11.39%, I 2 level3 = 77.67%) of depressive symptomatology in patients receiving psilocybin in addition to supportive therapy compared to baseline measurements. The decrease was also marked when compared to placebo ( p-value = 0.032). The results remained significant even when a secondary analysis assessed the effect in various time intervals since the administration of psilocybin.
Conclusion: This systematic review and meta-analysis substantiate the claim that psilocybin is superior in treating depression compared to established psychotherapy alone used for treating depression. This finding warrants further studies with larger sample sizes and across a longer timeframe.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... | 2020 | Systematic review | n = 188 |
| The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression | 2020 | Meta-analysis | n = 117 |
| Psychedelics in the treatment of unipolar mood disorders: a systematic review Patients with broadly defined unipolar mood disorders | 2016 | Systematic review | n = 423 |
| Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... | 2023 | Systematic review with meta-analysis | n = 14 |
| Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Patients with life-threatening diseases and symptoms of anxiety or depression | 2018 | Systematic review | n = 445 |