1. In adults with treatment-resistant depression, a 25mg dose of psilocybin significantly improved Montgomery-Asberg Depression Rating Scale (MADRS) score at three-week follow-up.
2. A 25mg psilocybin dose was superior to a 1mg or 10mg dose in reducing MADRS scores.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Psilocybins have demonstrated antidepressant effects in previous studies of patients with life-limiting cancers. The study examined the efficacy and safety of psilocybin at various doses in patients with treatment-resistant depression. A decrease in the MADRS was seen in the 25mg group, 10mg group, and 1mg group at three weeks of follow-up. The difference between the 25mg group and the 1mg group was significant, in favor of the former. The incidence of remission was highest in the 25mg group and significant between the 25mg and 1mg groups. Adverse events occurred in all three groups. The adverse event rate was highest in the 25mg group, followed by the 10mg and 1mg groups. Adverse events included headache, nausea, dizziness, and fatigue. The serious adverse events reported included suicidal ideation, intentional self-injury, and hospitalization. No clinically significant changes in the participant’s vital signs, lab tests, or electrocardiograms (ECGs) were observed during the trial. The limitations of this study include the short duration of follow-up and the concurrent treatment of depression with therapy during the study, which may lead to overestimating the efficacy of the intervention.
Relevant Reading: Trial of psilocybin versus escitalopram for depression
In-Depth [randomized controlled trial]: This double-blind randomized control trial examined the efficacy and safety of a synthetic, proprietary formulation of psilocybins administered with psychological support for patients with treatment-resistant depression. Patients over the age of 18 who met the criteria for treatment-resistant depression were included, which includes two to four trials of adequate dose and duration were included in the study. All patients were required to taper and discontinue all central nervous system-affecting medications at least two weeks before psilocybin administration. Patients were then randomized to receive 25mg, 10mg, or 1mg (control) of psilocybin. A total of 233 participants were enrolled and received treatment. The mean MADRS scores at baseline were 31.9 in the 25mg group, 33.0 in the 10mg group, and 32.7 in the 1mg group. The least-squares mean change from baseline to week three in the MADRS score was -12.0 in the 25mg group, -7.9 in the 10mg group, and -5.4 in the 1mg group. The difference in change between the 25mg group and 1mg group was -6.6 (95% Confidence interval [CI], -10.2 to -2.9; p<0.001), and the difference between the 25mg group and 1mg group was -2.5 (95% CI, -6.2 to 1.2; p=0.18). The incidence of remission at week three was 29% for the 25mg group, 9% for the 10mg group, and 8% in the 1mg group. The odds ratio for remission between the 25mg group compared to the 1mg group was 4.8 (95% CI, 1.8 to 12.9). Adverse events occurred in 84% of the 25mg group, 75% in the 10mg group, and 72% in the 1mg group. Most of the adverse events were reported on the first day of psilocybin administration. After day two up to week three, severe adverse events were reported in 9% of individuals in the 25mg group, 7% of individuals in the 10mg group, and 1% of individuals in the 1mg group. In summary, this study demonstrates that psilocybins may improve symptoms of treatment-resistant depression.
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