Trajectory of Antidepressant Effects after Single- or Two-Dose Administration of Psilocybin: A Systematic Review and Multivariate Meta-Analysis
Chia‐ling Yu, Chih‐sung Liang, Fu‐chi Yang, Yu‐kang Tu, Chih‐wei Hsu, André F. Carvalho, Brendon Stubbs, Trevor Thompson, Chia‐kuang Tsai, Ta‐chuan Yeh, Szu‐nian Yang, Jae Il Shin, Che‐sheng Chu, Ping‐tao Tseng, Kuan‐pin Su
Journal of Clinical Medicine February 11, 2022 DOI: 10.3390/jcm11040938 via OpenAlex
Summary
AI-generated from the abstractA meta-analysis of ten studies found that one or two doses of psilocybin produce rapid and sustained antidepressant effects lasting up to six months. Depressive symptoms decreased substantially, with the largest effect at one week (standardized mean difference -1.74) and a still-large effect at six months (-1.12). Higher doses and two sessions were linked to greater improvement. Psilocybin raised systolic blood pressure by 19.00 mmHg and diastolic by 8.66 mmHg, but discontinuation rates and heart rate changes were similar to placebo. The findings suggest psilocybin has favorable cardiovascular safety and acceptability for treating depression.
Study at a glance
| Characteristics | Systematic review and meta-analysis Randomized Placebo-controlled Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Placebo Meta-analysis Discontinuation Confidence interval |
| Citations | 37 |
| Key finding | Single- or two-dose psilocybin administration produces rapid and sustained antidepressant effects for up to six months with cardiovascular safety and acceptability comparable to placebo. |
Abstract
We examined the cardiovascular safety, acceptability, and trajectory of the antidepressant effects of psilocybin after single- or two-dose administration. Four major electronic databases were systematically searched. Data were pooled using a multivariate random-effects meta-analysis. Primary outcomes were changes in depressive symptoms. Secondary outcomes were cardiovascular safety and acceptability. Ten studies were included. The estimated effect sizes (standardized mean difference (SMD) with 95% confidence intervals) for psilocybin were −0.75 (−1.15 to −0.35) on day 1, −1.74 (−2.15 to −1.32) at 1 week, −1.35 (−1.77 to −0.93) at 1 month, −0.91 (−1.31 to −0.51) at 3 months, and −1.12 (−1.56 to −0.68) at 6 months. Higher doses and two sessions of psilocybin treatment were significantly associated with superior antidepressant effects. The all-cause discontinuation and heart rate after psilocybin administration were comparable to placebo; meanwhile, psilocybin increased systolic and diastolic blood pressure by 19.00 mmHg and 8.66 mmHg, respectively. There were no significant differences between SMD derived from placebo-controlled trials compared to those from pre–post changes and SMD in randomized controlled trials (RCTs) compared to those in non-RCTs. The present study demonstrates that single- or two-dose psilocybin administration has rapid and sustained antidepressant effects for up to 6 months, with favorable cardiovascular safety and acceptability.