Psilocybin Shows Potential for Depression Treatment, Meta-Analysis Finds
High-dose psilocybin demonstrated an effect similar to escitalopram for the treatment of depressive symptoms in a recent systematic review and meta-analysis published in The BMJ.
Researchers investigated the comparative effectiveness of oral monotherapy with psychedelics—specifically psilocybin, 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), or ayahuasca—and escitalopram in randomized controlled trials published before October 12, 2023. Participants in psychedelic trials had no concomitant use of antidepressants. Depression outcomes were measured using the 17-item Hamilton Rating Scale for Depression.
The systematic review and meta-analysis included 15 psychedelic trials spanning 811 adults with acute depressive symptoms and 5 escitalopram trials involving 1968 adults with acute depressive symptoms.
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Placebo responses in the psychedelic trials were lower than placebo responses in the escitalopram trials, according to the study. Consequently, most of the psychedelics tended to outperform placebo for improving depressive symptoms in the psychedelic trials. Nevertheless, high-dose psilocybin was the only psychedelic treatment that performed better than placebo in reducing depressive symptoms in the escitalopram trials. The standardized mean difference was 0.3, signaling a small effect size for psilocybin.
In secondary outcome analyses, none of the interventions was associated with higher all-cause discontinuation or severe adverse events, such as death, hospital admission, or suicide attempt, compared with placebo.
Although high-dose psilocybin appears to offer the potential for treating depressive symptoms, study designs may have overestimated the effectiveness, researchers wrote in the study conclusion.
“Our analysis suggested that the standardized mean difference of high-dose psilocybin was similar to that of current antidepressant drugs, showing a small effect size,” the authors continued. “Improved blinding methods and standardized psychotherapies can help researchers to better estimate the efficacy of psychedelics for depressive symptoms and other psychiatric conditions.”
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