Efficacy and safety of psilocybin in the treatment of Major Depressive Disorder (MDD): A dose-response network meta-analysis of randomized placebo-controlled clinical trials.
Damian Swieczkowski, Aleksander Kwaśny, Michal Pruc, Zuzanna Gaca, Lukasz Szarpak, Wiesław Jerzy Cubała
Psychiatry Research February 1, 2025 DOI: 10.1016/j.psychres.2024.116337 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and dose-response network meta-analysis Randomized Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 389 |
| Population | Adult patients with Major Depressive Disorder |
| Intervention | Psilocybin |
| Dose | 25 mg, 0.215 mg/kg, 10 mg |
| Topics | Depression Psilocybin |
| Keywords | Psilocybin therapy Depression treatment Psychedelic medicine Mental health research Clinical trials Antidepressive agents Psychedelic drug Rapid-acting antidepressant |
| Citations | 17 |
| Key findings | Psilocybin at a 25 mg dose significantly reduces depression symptoms compared to placebo at Day 8 and Day 15, with a higher risk of nausea. |
Abstract
Selecting the optimal dose of psilocybin for treating Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD) is crucial for clinical development and regulatory approval. This meta-analysis evaluates psilocybin's efficacy and safety in treating MDD to determine the optimal dose and timing for clinical trials. A systematic review and Dose-Response Network Meta-Analysis (NMA) of Randomized Placebo-Controlled Clinical Trials (RCTs) registered with PROSPERO was conducted. Databases searched included Embase, PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar, up to July 2024. The PICOS framework defined eligibility criteria: P: adult patients with MDD; I: psilocybin; C: placebo; O: changes in MADRS scores at Days 2, 8 and 15, and adverse events; S: RCT. Independent researchers performed data extraction and bias assessment. From 5419 search results, three RCTs involving 389 patients were included. Psilocybin significantly reduced symptoms compared to placebo at Day 8 (MD = -7.42; 95 % CI:10.07 to -4.78; p < 0.001) and Day 15 (MD = -9.55; 95 % CI:12.44 to -6.65; p < 0.001), without significant effects on Day 2. The NMA indicated that a 25 mg dose was the most effective, with a SUCRA value of 92.25 %, compared to doses of 0.215 mg/kg and 10 mg. However, psilocybin was associated with a higher risk of adverse events, particularly nausea (RR = 8.35; p < 0.001). This meta-analysis supports psilocybin's efficacy in treating MDD, particularly at a 25 mg dose, showing a time-dependent therapeutic effect. The recommended timing of efficacy evaluation by regulatory authorities is validated by this evidence, underscoring its importance in clinical trial design for psychedelic substances.
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 |