High-Dose Psilocybin Shows Promising Results for Depression

TOPLINE:
High-dose psilocybin is associated with greater relief from depressive symptoms than placebo or escitalopram, with no increased risk for severe adverse events, a new meta-analysis suggests.
METHODOLOGY:
Researchers conducted a network meta-analysis to evaluate the comparative effectiveness of oral monotherapy with psychedelics vs escitalopram in patients with clinically diagnosed depression.
The meta-analysis included 811 participants (mean age, 42.49 years; 54.2% women) with clinically diagnosed depression across 15 psychedelic trials and 1968 participants (mean age, 39.35 years; 62.5% women) across five escitalopram trials.
Trials evaluated oral monotherapy with psychedelics (psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine [MDMA], and ayahuasca), fixed-dose escitalopram (up to 20 mg/d) vs placebo, and psychedelic vs escitalopram monotherapy.
The primary outcome was a change in depressive symptoms from baseline.
TAKEAWAY:
Placebo responses in antidepressant trials (mean difference, 3.79; 95% CI, 0.77-6.80) and extremely low-dose psilocybin (mean difference, 3.96; 95% CI, 0.61-7.17) were better than those in psychedelic trials.
High-dose psilocybin (≥ 20 mg) performed better than placebo in the antidepressant trials (mean difference, > 3). However, when comparing high-dose psilocybin with the placebo used in antidepressant trials, the effect size was smaller. The standardized mean difference dropped from 0.88 to 0.31, indicating that the effect of high-dose psilocybin was similar to that of current antidepressants.
High-dose psilocybin was associated with a greater response than escitalopram at 10 mg (4.66; 95% CI, 1.36-7.74) and 20 mg (4.69; 95% CI, 1.64-7.54).
No interventions were associated with an increased risk for all-cause discontinuation or severe adverse events.
IN PRACTICE:
“Taken together, our study findings suggest that among psychedelic treatments, high-dose psilocybin is more likely to reach the minimal important difference for depressive symptoms in studies with adequate blinding design, while the effect size of psilocybin was similar to that of current antidepressant drugs, showing a mean standardized mean difference of 0.3,” the authors wrote.
SOURCE:
The study was led by Tien-Wei Hsu, MD, I-Shou University and Kaohsiung Medical University, Kaohsiung City, Taiwan. It was published online on August 21 in The BMJ. 
LIMITATIONS:
The study did not assess long-term effects of the interventions. Participants in the MDMA trials were primarily diagnosed with posttraumatic stress disorder, which may not be representative of the general population with depressive symptoms. Moreover, the sample size of the psychedelic trials was small. Using extremely low-dose psychedelics as a reference group may have eliminated some pharmacologic effects as these doses cannot be considered a placebo.
DISCLOSURES:
The study was supported by grants from the National Science and Technology Council. The authors declared no financial relationships with any organizations outside the submitted work in the past 3 years. Full disclosures are available in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 
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